Metabolism of water-soluble vitamins and cofactors (Homo sapiens)

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Vitamins are a diverse group of organic compounds, required in small amounts in the diet. They have distinct biochemical roles, often as coenzymes, and are either not synthesized or synthesized only in limited amounts by human cells. Vitamins are classified according to their solubility, either fat-soluble or water-soluble. The physiological processes dependent on vitamin-requiring reactions include many aspects of intermediary metabolism, vision, bone formation, and blood coagulation, and vitamin deficiencies are associated with a correspondingly diverse and severe group of diseases.

Water-soluble vitamins include ascorbate (vitamin C) and the members of the B group: thiamin (vitamin B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12). Metabolic processes annotated here include the synthesis of thiamin pyrophosphate (TPP) from thiamin (B1), the synthesis of FMN and FAD from riboflavin (B2), the synthesis of nicotinic acid (niacin - B3) from tryptophan, the synthesis of Coenzyme A from pantothenate (B5), and features of the metabolism of folate (B9).Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=196849</div>

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	113093	view	11:15, 2 November 2020	ReactomeTeam	Reactome version 74
	112327	view	15:25, 9 October 2020	ReactomeTeam	Reactome version 73
	101226	view	11:12, 1 November 2018	ReactomeTeam	reactome version 66
	100764	view	20:38, 31 October 2018	ReactomeTeam	reactome version 65
	100308	view	19:15, 31 October 2018	ReactomeTeam	reactome version 64
	99854	view	15:58, 31 October 2018	ReactomeTeam	reactome version 63
	99412	view	14:35, 31 October 2018	ReactomeTeam	reactome version 62 (2nd attempt)
	99099	view	12:39, 31 October 2018	ReactomeTeam	reactome version 62
	94004	view	13:50, 16 August 2017	ReactomeTeam	reactome version 61
	93616	view	11:28, 9 August 2017	ReactomeTeam	reactome version 61
	86724	view	09:24, 11 July 2016	ReactomeTeam	reactome version 56
	83083	view	09:55, 18 November 2015	ReactomeTeam	Version54
	81407	view	12:56, 21 August 2015	ReactomeTeam	Version53
	76875	view	08:14, 17 July 2014	ReactomeTeam	Fixed remaining interactions
	76580	view	11:56, 16 July 2014	ReactomeTeam	Fixed remaining interactions
	75913	view	09:56, 11 June 2014	ReactomeTeam	Re-fixing comment source
	75613	view	10:47, 10 June 2014	ReactomeTeam	Reactome 48 Update
	74968	view	13:49, 8 May 2014	Anwesha	Fixing comment source for displaying WikiPathways description
	74612	view	08:39, 30 April 2014	ReactomeTeam	Reactome46
	44904	view	10:24, 6 October 2011	MartijnVanIersel	Ontology Term : 'metabolic pathway of cofactors and vitamins' added !
	42173	view	23:38, 4 March 2011	MaintBot	Modified categories
	42075	view	21:55, 4 March 2011	MaintBot	Automatic update
	39883	view	05:54, 21 January 2011	MaintBot	New pathway

External references

DataNodes

View all...

Name	Type	Database reference	Comment
(4Fe-4S)(2+) [cytosol]	Metabolite	CHEBI:33722 (ChEBI)
10-FTHFPG	Metabolite	CHEBI:28010 (ChEBI)
2xAOX1:cofactors	Complex	REACT_164135 (Reactome)
2xENPP1	Complex	REACT_11259 (Reactome)
2xGSTOs	Complex	REACT_11879 (Reactome)
2xMMAA:2xMUT:AdoCbl	Complex	REACT_161342 (Reactome)
2xMMAA:2xMUT	Complex	REACT_160828 (Reactome)
2xMOCS2-CO-S(1-):2xMOCS2B	Complex	REACT_25716 (Reactome)
2xMOCS2A:2xMOCS2B	Complex	REACT_25714 (Reactome)
2xMTHFD1	Complex	REACT_11452 (Reactome)
2xMTHFR	Complex	REACT_11644 (Reactome)
2xNAPRT1	Complex	REACT_17164 (Reactome)
2xNFS1:2xPXLP	Complex	REACT_26174 (Reactome)
2xPDXK:2xZn2+	Complex	REACT_26520 (Reactome)
2xPNPO:2xFMN	Complex	REACT_26517 (Reactome)
2xPPCS	Complex	REACT_11296 (Reactome)
2xTPK1:Mg2+	Complex	REACT_11433 (Reactome)
2xTRAP	Complex	REACT_11966 (Reactome)
3xGPHN:3xMg2+	Complex	REACT_26924 (Reactome)
3xMMAB	Complex	REACT_165069 (Reactome)
3xPPCDC:3xFMN	Complex	REACT_11983 (Reactome)
4x(Btn-PC:Mn2+)	Complex	REACT_165274 (Reactome)
4x(PC:Mn2+)	Complex	REACT_165431 (Reactome)
4xNADK:Zn2+	Complex	REACT_11972 (Reactome)
4xNMNAT3:4xMg2+	Complex	REACT_11927 (Reactome)
4xSHMT1	Complex	REACT_3102 (Reactome)
5,10-MTHFPG	Metabolite	CHEBI:65049 (ChEBI)
5,10-MetTHFPG	Metabolite	CHEBI:60473 (ChEBI)
6x(Btn-MCCC1:MCCC2)	Complex	REACT_164554 (Reactome)
6x(Btn-PCCA:PCCB)	Complex	REACT_164655 (Reactome)
6x(PCCA:PCCB)	Complex	REACT_165540 (Reactome)
6xMCCC1:6xMCCC2	Complex	REACT_164465 (Reactome)
6xNMNAT1:6xZn2+	Complex	REACT_11954 (Reactome)
AASDHPPT	Protein	Q9NRN7 (Uniprot-TrEMBL)
ABCC1	Protein	P33527 (Uniprot-TrEMBL)
ACACA,B:2Mn2+	Complex	REACT_164775 (Reactome)
ACP5 [cytosol]	Protein	P13686 (Uniprot-TrEMBL)
ACS	Metabolite	CHEBI:29044 (ChEBI)
ADP	Metabolite	CHEBI:16761 (ChEBI)
AMN [endosome membrane]	Protein	Q9BXJ7 (Uniprot-TrEMBL)
AMN [plasma membrane]	Protein	Q9BXJ7 (Uniprot-TrEMBL)
AMP	Metabolite	CHEBI:16027 (ChEBI)
AOX1 [cytosol]	Protein	Q06278 (Uniprot-TrEMBL)
ATP	Metabolite	CHEBI:15422 (ChEBI)
AdoCbl [mitochondrial matrix]	Metabolite	CHEBI:18408 (ChEBI)
AdoCbl	Metabolite	CHEBI:18408 (ChEBI)
AdoHcy	Metabolite	CHEBI:16680 (ChEBI)
AdoMet	Metabolite	CHEBI:15414 (ChEBI)
B12r [cytosol]	Metabolite	CHEBI:16304 (ChEBI)
B12r	Metabolite	CHEBI:16304 (ChEBI)
B12s [cytosol]	Metabolite	CHEBI:15982 (ChEBI)
B12s	Metabolite	CHEBI:15982 (ChEBI)
BCTN	Metabolite	CHEBI:27870 (ChEBI)
BTD	Protein	P43251 (Uniprot-TrEMBL)
Btn-ACACA,B:2Mn2+	Complex	REACT_164383 (Reactome)
Btn-MCCC1 [mitochondrial matrix]	Protein	Q96RQ3 (Uniprot-TrEMBL)
Btn-MCCC1 [cytosol]	Protein	Q96RQ3 (Uniprot-TrEMBL)
Btn-PC [mitochondrial matrix]	Protein	P11498 (Uniprot-TrEMBL)
Btn-PC [cytosol]	Protein	P11498 (Uniprot-TrEMBL)
Btn-PCCA [mitochondrial matrix]	Protein	P05165 (Uniprot-TrEMBL)
Btn-PCCA [cytosol]	Protein	P05165 (Uniprot-TrEMBL)
Btn	Metabolite	CHEBI:15956 (ChEBI)
CD320 [endosome membrane]	Protein	Q9NPF0 (Uniprot-TrEMBL)
CD320	Protein	Q9NPF0 (Uniprot-TrEMBL)
CNCbl	Metabolite	CHEBI:17439 (ChEBI)
CO2	Metabolite	CHEBI:16526 (ChEBI)
COASY	Protein	Q13057 (Uniprot-TrEMBL)
CUBN [endosome membrane]	Protein	O60494 (Uniprot-TrEMBL)
CUBN [plasma membrane]	Protein	O60494 (Uniprot-TrEMBL)
CUBN:AMN:GIF:Cbl	Complex	REACT_165531 (Reactome)
CUBN:AMN	Complex	REACT_14330 (Reactome)
CUBN:AMN	Complex	REACT_165497 (Reactome)
CYB5A [mitochondrial outer membrane]	Protein	P00167 (Uniprot-TrEMBL)
CYB5A:ferriheme	Complex	REACT_11821 (Reactome)
CYB5A:heme	Complex	REACT_11661 (Reactome)
CYB5R3:FAD	Complex	REACT_11367 (Reactome)
Cbl [endosome]	Metabolite	CHEBI:28911 (ChEBI)
Cbl [extracellular region]	Metabolite	CHEBI:28911 (ChEBI)
Cbl [lysosomal lumen]	Metabolite	CHEBI:28911 (ChEBI)
Cbl	Metabolite	CHEBI:28911 (ChEBI)
CoA-SH	Metabolite	CHEBI:15346 (ChEBI)
Cys	Metabolite	CHEBI:17561 (ChEBI)
CysS-MOCS3 [cytosol]	Protein	O95396 (Uniprot-TrEMBL)
DA-NAD+	Metabolite	CHEBI:18304 (ChEBI)
DHF	Metabolite	CHEBI:15633 (ChEBI)
DHFR	Protein	P00374 (Uniprot-TrEMBL)
DHFR	Protein	REACT_161383 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
DHvitC	Metabolite	CHEBI:17242 (ChEBI)
DP-CoA	Metabolite	CHEBI:15468 (ChEBI)
ENPP1 [plasma membrane]	Protein	P22413 (Uniprot-TrEMBL)
FAD [cytosol]	Metabolite	CHEBI:16238 (ChEBI)
FAD [mitochondrial outer membrane]	Metabolite	CHEBI:16238 (ChEBI)
FAD	Metabolite	CHEBI:16238 (ChEBI)
FASN	Protein	P49327 (Uniprot-TrEMBL)
FLAD1	Protein	Q8NFF5 (Uniprot-TrEMBL)
FMN [cytosol]	Metabolite	CHEBI:17621 (ChEBI)
FMN	Metabolite	CHEBI:17621 (ChEBI)
FOLA	Metabolite	CHEBI:27470 (ChEBI)
FPGS-1	Protein	Q05932-1 (Uniprot-TrEMBL)
FPGS-2	Protein	Q05932-2 (Uniprot-TrEMBL)
FeHM [mitochondrial outer membrane]	Metabolite	CHEBI:36144 (ChEBI)
Food proteins:Cbl	Complex	REACT_165372 (Reactome)
Food proteins		REACT_164876 (Reactome)
GIF [endosome]	Protein	P27352 (Uniprot-TrEMBL)
GIF [extracellular region]	Protein	P27352 (Uniprot-TrEMBL)
GIF [lysosomal lumen]	Protein	P27352 (Uniprot-TrEMBL)
GIF:Cbl	Complex	REACT_164547 (Reactome)
GIF:Cbl	Complex	REACT_164635 (Reactome)
GIF:Cbl	Complex	REACT_164904 (Reactome)
GIF	Protein	P27352 (Uniprot-TrEMBL)
GLUT1,3	Protein	REACT_11567 (Reactome)
GPHN [plasma membrane]	Protein	Q9NQX3 (Uniprot-TrEMBL)
GSH	Metabolite	CHEBI:16856 (ChEBI)
GSSG	Metabolite	CHEBI:17858 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
Glu	Metabolite	CHEBI:16015 (ChEBI)
Gly	Metabolite	CHEBI:15428 (ChEBI)
H+	Metabolite	CHEBI:15378 (ChEBI)
H2O2	Metabolite	CHEBI:16240 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HCN	Metabolite	CHEBI:18407 (ChEBI)
HCOOH	Metabolite	CHEBI:30751 (ChEBI)
HCYS	Metabolite	CHEBI:17230 (ChEBI)
HLCS	Protein	P50747 (Uniprot-TrEMBL)
L-Ala	Metabolite	CHEBI:16977 (ChEBI)
L-Gln	Metabolite	CHEBI:18050 (ChEBI)
L-Glu	Metabolite	CHEBI:16015 (ChEBI)
L-Lys	Metabolite	CHEBI:18019 (ChEBI)
L-MM-CoA	Metabolite	CHEBI:15465 (ChEBI)
L-Met	Metabolite	CHEBI:16643 (ChEBI)
L-Ser	Metabolite	CHEBI:17115 (ChEBI)
LMBRD1	Protein	Q9NUN5 (Uniprot-TrEMBL)
MCCC1 [cytosol]	Protein	Q96RQ3 (Uniprot-TrEMBL)
MCCC2 [cytosol]	Protein	Q9HCC0 (Uniprot-TrEMBL)
MCCC2 [mitochondrial matrix]	Protein	Q9HCC0 (Uniprot-TrEMBL)
MDASC	Metabolite	CHEBI:16504 (ChEBI)
MMAA [mitochondrial matrix]	Protein	Q8IVH4 (Uniprot-TrEMBL)
MMAB [mitochondrial matrix]	Protein	Q96EY8 (Uniprot-TrEMBL)
MMACHC [cytosol]	Protein	Q9Y4U1 (Uniprot-TrEMBL)
MMACHC:B12r	Complex	REACT_164491 (Reactome)
MMACHC:MMADHC:B12r	Complex	REACT_164855 (Reactome)
MMACHC:MMADHC	Complex	REACT_164368 (Reactome)
MMACHC	Protein	Q9Y4U1 (Uniprot-TrEMBL)
MMADHC [cytosol]	Protein	Q9H3L0 (Uniprot-TrEMBL)
MMADHC	Protein	Q9H3L0 (Uniprot-TrEMBL)
MOCOS [cytosol]	Protein	Q96EN8 (Uniprot-TrEMBL)
MOCOS:PXLP	Complex	REACT_26664 (Reactome)
MOCS1-1 [cytosol]	Protein	Q9NZB8-1 (Uniprot-TrEMBL)
MOCS1A [cytosol]	Protein	Q9NZB8-5 (Uniprot-TrEMBL)
MOCS2 [cytosol]	Protein	O96007 (Uniprot-TrEMBL)
MOCS2 [cytosol]	Protein	O96033 (Uniprot-TrEMBL)
MOCS2	Protein	O96033 (Uniprot-TrEMBL)
MOCS3 [cytosol]	Protein	O95396 (Uniprot-TrEMBL)
MOCS3-S-S(1-):Zn2+	Complex	REACT_25705 (Reactome)
MOCS3:Zn2+ (ox.)	Complex	REACT_26398 (Reactome)
MOCS3:Zn2+ (red.)	Complex	REACT_27010 (Reactome)
MPT [cytosol]	Metabolite	CHEBI:44074 (ChEBI)
MPT	Metabolite	CHEBI:58698 (ChEBI)
MTHF	Metabolite	CHEBI:15641 (ChEBI)
MTHFD1 [cytosol]	Protein	P11586 (Uniprot-TrEMBL)
MTHFPG	Metabolite	CHEBI:63907 (ChEBI)
MTHFR [cytosol]	Protein	P42898 (Uniprot-TrEMBL)
MTR [cytosol]	Protein	Q99707 (Uniprot-TrEMBL)
MTRR [cytosol]	Protein	Q9UBK8 (Uniprot-TrEMBL)
MTRR:MTR(B12r)	Complex	REACT_160699 (Reactome)
MTRR:MTR(B12s)	Complex	REACT_164391 (Reactome)
MTRR:MTR(MeCbl)	Complex	REACT_160519 (Reactome)
MTRR:MTR	Complex	REACT_164139 (Reactome)
MUT [mitochondrial matrix]	Protein	P22033 (Uniprot-TrEMBL)
MeCbl [cytosol]	Metabolite	CHEBI:28115 (ChEBI)
Mg2+ [Golgi membrane]	Metabolite	CHEBI:18420 (ChEBI)
Mg2+ [cytosol]	Metabolite	CHEBI:18420 (ChEBI)
Mg2+	Metabolite	CHEBI:18420 (ChEBI)
Mn2+ [cytosol]	Metabolite	CHEBI:18291 (ChEBI)
Mn2+ [mitochondrial matrix]	Metabolite	CHEBI:18291 (ChEBI)
MoCo	Metabolite	CHEBI:25372 (ChEBI)
MoO4(2-)	Metabolite	CHEBI:36264 (ChEBI)
MyrG-CYB5R3(2-301) [mitochondrial outer membrane]	Protein	P00387 (Uniprot-TrEMBL)
NAD+	Metabolite	CHEBI:15846 (ChEBI)
NADH	Metabolite	CHEBI:16908 (ChEBI)
NADK [cytosol]	Protein	O95544 (Uniprot-TrEMBL)
NADP+	Metabolite	CHEBI:18009 (ChEBI)
NADPH	Metabolite	CHEBI:16474 (ChEBI)
NADSYN1 [cytosol]	Protein	Q6IA69 (Uniprot-TrEMBL)
NADSYN1 homohexamer	Complex	REACT_11254 (Reactome)
NAM	Metabolite	CHEBI:17154 (ChEBI)
NAMD		REACT_11492 (Reactome)
NAMPT	Protein	P43490 (Uniprot-TrEMBL)
NAPRT1 [cytosol]	Protein	Q6XQN6 (Uniprot-TrEMBL)
NCA	Metabolite	CHEBI:15940 (ChEBI)
NFS1-2 [cytosol]	Protein	Q9Y697-2 (Uniprot-TrEMBL)
NH3	Metabolite	CHEBI:16134 (ChEBI)
NH4+	Metabolite	CHEBI:28938 (ChEBI)
NMNAT1 [nucleoplasm]	Protein	Q9HAN9 (Uniprot-TrEMBL)
NMNAT2 (Mg2+)	Complex	REACT_11885 (Reactome)
NMNAT2 [Golgi membrane]	Protein	Q9BZQ4 (Uniprot-TrEMBL)
NMNAT3 [cytosol]	Protein	Q96T66 (Uniprot-TrEMBL)
Na+	Metabolite	CHEBI:29101 (ChEBI)
Nicotinate D-ribonucleotide	Metabolite	CHEBI:15763 (ChEBI)
O-phosphopantetheine-L-serine-FASN	Protein	P49327 (Uniprot-TrEMBL)
O2	Metabolite	CHEBI:15379 (ChEBI)
PANK1/3/4	Protein	REACT_11650 (Reactome)
PANK2(111-570)	Protein	Q9BZ23 (Uniprot-TrEMBL)
PAP	Metabolite	CHEBI:17985 (ChEBI)
PC [cytosol]	Protein	P11498 (Uniprot-TrEMBL)
PCCA [cytosol]	Protein	P05165 (Uniprot-TrEMBL)
PCCB [cytosol]	Protein	P05166 (Uniprot-TrEMBL)
PCCB [mitochondrial matrix]	Protein	P05166 (Uniprot-TrEMBL)
PDX	Metabolite	CHEBI:16709 (ChEBI)
PDXK [cytosol]	Protein	O00764 (Uniprot-TrEMBL)
PDXP	Metabolite	CHEBI:28803 (ChEBI)
PDXate	Metabolite	CHEBI:17405 (ChEBI)
PNPO(1-216) [cytosol]	Protein	Q9NVS9 (Uniprot-TrEMBL)
PPANT	Metabolite	CHEBI:16858 (ChEBI)
PPC	Metabolite	CHEBI:15769 (ChEBI)
PPCDC [cytosol]	Protein	Q96CD2 (Uniprot-TrEMBL)
PPCS [cytosol]	Protein	Q9HAB8 (Uniprot-TrEMBL)
PPP	Metabolite	CHEBI:15266 (ChEBI)
PPanK	Metabolite	CHEBI:15905 (ChEBI)
PPi	Metabolite	CHEBI:29888 (ChEBI)
PRPP	Metabolite	CHEBI:17111 (ChEBI)
PRSS1,3,CTRB1,2	Protein	REACT_165248 (Reactome)
PXA	Metabolite	CHEBI:16410 (ChEBI)
PXAP	Metabolite	CHEBI:18335 (ChEBI)
PXL	Metabolite	CHEBI:17310 (ChEBI)
PXLP [cytosol]	Metabolite	CHEBI:18405 (ChEBI)
PXLP-SHMT1(1-483) [cytosol]	Protein	P34896 (Uniprot-TrEMBL)
PXLP	Metabolite	CHEBI:18405 (ChEBI)
PanK	Metabolite	CHEBI:7916 (ChEBI)
Pi	Metabolite	CHEBI:18367 (ChEBI)
Precursor Z	Metabolite	CHEBI:59648 (ChEBI)
QPRT	Protein	Q15274 (Uniprot-TrEMBL)
QUIN	Metabolite	CHEBI:46828 (ChEBI)
RFK(1-162) [cytosol]	Protein	Q969G6 (Uniprot-TrEMBL)
RFK:Mg2+	Complex	REACT_11696 (Reactome)
RIB	Metabolite	CHEBI:17015 (ChEBI)
SLC19A1	Protein	P41440 (Uniprot-TrEMBL)
SLC19A2/3	Protein	REACT_11312 (Reactome)
SLC25A16	Protein	P16260 (Uniprot-TrEMBL)
SLC25A32	Protein	Q9H2D1 (Uniprot-TrEMBL)
SLC46A1	Protein	Q96NT5 (Uniprot-TrEMBL)
SLC52A3	Protein	Q9NQ40 (Uniprot-TrEMBL)
SLC5A6	Protein	Q9Y289 (Uniprot-TrEMBL)
SOG-MOCS2 [cytosol]	Protein	O96033 (Uniprot-TrEMBL)
SOG-MOCS2	Protein	O96033 (Uniprot-TrEMBL)
SUCC-CoA	Metabolite	CHEBI:15380 (ChEBI)
SVCT1/2	Protein	REACT_11407 (Reactome)
TCN1 [extracellular region]	Protein	P20061 (Uniprot-TrEMBL)
TCN1:Cbl	Complex	REACT_165389 (Reactome)
TCN1	Protein	P20061 (Uniprot-TrEMBL)
TCN2 [endosome]	Protein	P20062 (Uniprot-TrEMBL)
TCN2 [extracellular region]	Protein	P20062 (Uniprot-TrEMBL)
TCN2 [lysosomal lumen]	Protein	P20062 (Uniprot-TrEMBL)
TCN2:Cbl:CD320	Complex	REACT_165315 (Reactome)
TCN2:Cbl	Complex	REACT_164532 (Reactome)
TCN2:Cbl	Complex	REACT_164840 (Reactome)
TCN2:Cbl	Complex	REACT_165015 (Reactome)
TCN2	Protein	P20062 (Uniprot-TrEMBL)
TDPK		REACT_26649 (Reactome)
THF	Metabolite	CHEBI:15635 (ChEBI)
THFPG	Metabolite	CHEBI:28624 (ChEBI)
THMN	Metabolite	CHEBI:18385 (ChEBI)
THTPA [cytosol]	Protein	Q9BU02 (Uniprot-TrEMBL)
THTPA:Mg2+	Complex	REACT_26403 (Reactome)
TPK1 [cytosol]	Protein	Q9H3S4 (Uniprot-TrEMBL)
ThDP	Metabolite	CHEBI:9532 (ChEBI)
ThTP	Metabolite	CHEBI:9534 (ChEBI)
VitC	Metabolite	CHEBI:29073 (ChEBI)
Zn2+ [cytosol]	Metabolite	CHEBI:29105 (ChEBI)
Zn2+ [nucleoplasm]	Metabolite	CHEBI:29105 (ChEBI)
dADE	Metabolite	CHEBI:17319 (ChEBI)
hCBXs	Complex	REACT_164592 (Reactome)
hCBXs	Complex	REACT_165298 (Reactome)
heme [mitochondrial outer membrane]	Metabolite	CHEBI:17627 (ChEBI)
holo-MOCS1	Complex	REACT_26979 (Reactome)
sulfurated MoCo	Metabolite	CHEBI:60102 (ChEBI)
unknown peptidase		REACT_164093 (Reactome)
unknown peptidase		REACT_164602 (Reactome)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
	10-FTHFPG	Arrow	REACT_11074 (Reactome)
	10-FTHFPG	Arrow	REACT_11109 (Reactome)
10-FTHFPG			REACT_11205 (Reactome)
2xAOX1:cofactors		mim-catalysis	REACT_163723 (Reactome)
2xENPP1		mim-catalysis	REACT_11150 (Reactome)
2xGSTOs		mim-catalysis	REACT_11095 (Reactome)
	2xMMAA:2xMUT:AdoCbl	Arrow	REACT_163997 (Reactome)
2xMMAA:2xMUT:AdoCbl			REACT_19 (Reactome)
2xMMAA:2xMUT:AdoCbl		mim-catalysis	REACT_19 (Reactome)
	2xMMAA:2xMUT	Arrow	REACT_19 (Reactome)
2xMMAA:2xMUT			REACT_163997 (Reactome)
2xMOCS2-CO-S(1-):2xMOCS2B			REACT_25353 (Reactome)
2xMOCS2-CO-S(1-):2xMOCS2B		mim-catalysis	REACT_25353 (Reactome)
	2xMOCS2A:2xMOCS2B	Arrow	REACT_25353 (Reactome)
2xMTHFD1		mim-catalysis	REACT_11074 (Reactome)
2xMTHFD1		mim-catalysis	REACT_11109 (Reactome)
2xMTHFD1		mim-catalysis	REACT_11187 (Reactome)
2xMTHFD1		mim-catalysis	REACT_11192 (Reactome)
2xMTHFD1		mim-catalysis	REACT_11205 (Reactome)
2xMTHFR		mim-catalysis	REACT_11102 (Reactome)
2xNAPRT1		mim-catalysis	REACT_11132 (Reactome)
2xNFS1:2xPXLP		mim-catalysis	REACT_24937 (Reactome)
2xPDXK:2xZn2+		mim-catalysis	REACT_25109 (Reactome)
2xPDXK:2xZn2+		mim-catalysis	REACT_25295 (Reactome)
2xPDXK:2xZn2+		mim-catalysis	REACT_25323 (Reactome)
2xPNPO:2xFMN		mim-catalysis	REACT_25127 (Reactome)
2xPNPO:2xFMN		mim-catalysis	REACT_25348 (Reactome)
2xPPCS		mim-catalysis	REACT_11112 (Reactome)
2xTPK1:Mg2+		mim-catalysis	REACT_11233 (Reactome)
2xTRAP		mim-catalysis	REACT_11171 (Reactome)
3xGPHN:3xMg2+		mim-catalysis	REACT_25050 (Reactome)
3xMMAB		mim-catalysis	REACT_163830 (Reactome)
3xMMAB		mim-catalysis	REACT_163924 (Reactome)
3xPPCDC:3xFMN		mim-catalysis	REACT_11231 (Reactome)
	4x(Btn-PC:Mn2+)	Arrow	REACT_163950 (Reactome)
4x(PC:Mn2+)			REACT_163950 (Reactome)
4xNADK:Zn2+		mim-catalysis	REACT_11234 (Reactome)
4xNMNAT3:4xMg2+		mim-catalysis	REACT_11196 (Reactome)
4xSHMT1		mim-catalysis	REACT_11108 (Reactome)
4xSHMT1		mim-catalysis	REACT_11159 (Reactome)
	5,10-MTHFPG	Arrow	REACT_11192 (Reactome)
	5,10-MTHFPG	Arrow	REACT_11205 (Reactome)
5,10-MTHFPG			REACT_11074 (Reactome)
5,10-MTHFPG			REACT_11187 (Reactome)
	5,10-MetTHFPG	Arrow	REACT_11159 (Reactome)
	5,10-MetTHFPG	Arrow	REACT_11187 (Reactome)
5,10-MetTHFPG			REACT_11102 (Reactome)
5,10-MetTHFPG			REACT_11108 (Reactome)
5,10-MetTHFPG			REACT_11192 (Reactome)
	6x(Btn-MCCC1:MCCC2)	Arrow	REACT_163795 (Reactome)
	6x(Btn-PCCA:PCCB)	Arrow	REACT_163633 (Reactome)
6x(PCCA:PCCB)			REACT_163633 (Reactome)
6xMCCC1:6xMCCC2			REACT_163795 (Reactome)
6xNMNAT1:6xZn2+		mim-catalysis	REACT_11237 (Reactome)
AASDHPPT		mim-catalysis	REACT_11175 (Reactome)
ABCC1		mim-catalysis	REACT_163806 (Reactome)
ACACA,B:2Mn2+			REACT_163738 (Reactome)
ACS			REACT_11211 (Reactome)
	ADP	Arrow	REACT_11083 (Reactome)
	ADP	Arrow	REACT_11093 (Reactome)
	ADP	Arrow	REACT_11098 (Reactome)
	ADP	Arrow	REACT_11109 (Reactome)
	ADP	Arrow	REACT_11129 (Reactome)
	ADP	Arrow	REACT_11134 (Reactome)
	ADP	Arrow	REACT_11197 (Reactome)
	ADP	Arrow	REACT_11232 (Reactome)
	ADP	Arrow	REACT_11234 (Reactome)
	ADP	Arrow	REACT_163633 (Reactome)
	ADP	Arrow	REACT_163738 (Reactome)
	ADP	Arrow	REACT_163795 (Reactome)
	ADP	Arrow	REACT_163806 (Reactome)
	ADP	Arrow	REACT_163950 (Reactome)
	ADP	Arrow	REACT_25070 (Reactome)
	ADP	Arrow	REACT_25109 (Reactome)
	ADP	Arrow	REACT_25295 (Reactome)
	ADP	Arrow	REACT_25323 (Reactome)
	AMP	Arrow	REACT_11112 (Reactome)
	AMP	Arrow	REACT_11135 (Reactome)
	AMP	Arrow	REACT_11150 (Reactome)
	AMP	Arrow	REACT_11233 (Reactome)
	AMP	Arrow	REACT_25006 (Reactome)
	AMP	Arrow	REACT_25050 (Reactome)
ATP			REACT_11083 (Reactome)
ATP			REACT_11093 (Reactome)
ATP			REACT_11098 (Reactome)
ATP			REACT_11109 (Reactome)
ATP			REACT_11112 (Reactome)
ATP			REACT_11116 (Reactome)
ATP			REACT_11128 (Reactome)
ATP			REACT_11129 (Reactome)
ATP			REACT_11134 (Reactome)
ATP			REACT_11135 (Reactome)
ATP			REACT_11196 (Reactome)
ATP			REACT_11197 (Reactome)
ATP			REACT_11222 (Reactome)
ATP			REACT_11232 (Reactome)
ATP			REACT_11233 (Reactome)
ATP			REACT_11234 (Reactome)
ATP			REACT_11237 (Reactome)
ATP			REACT_163633 (Reactome)
ATP			REACT_163738 (Reactome)
ATP			REACT_163795 (Reactome)
ATP			REACT_163806 (Reactome)
ATP			REACT_163924 (Reactome)
ATP			REACT_163950 (Reactome)
ATP			REACT_25006 (Reactome)
ATP			REACT_25050 (Reactome)
ATP			REACT_25070 (Reactome)
ATP			REACT_25109 (Reactome)
ATP			REACT_25295 (Reactome)
ATP			REACT_25323 (Reactome)
	AdoCbl	Arrow	REACT_163924 (Reactome)
AdoCbl			REACT_163997 (Reactome)
	AdoHcy	Arrow	REACT_163988 (Reactome)
AdoMet			REACT_163988 (Reactome)
AdoMet			REACT_25068 (Reactome)
	B12r	Arrow	REACT_163697 (Reactome)
	B12r	Arrow	REACT_163721 (Reactome)
B12r			REACT_163830 (Reactome)
B12r			REACT_163898 (Reactome)
	B12s	Arrow	REACT_163830 (Reactome)
B12s			REACT_163924 (Reactome)
	BCTN	Arrow	REACT_163770 (Reactome)
	BCTN	Arrow	REACT_163820 (Reactome)
	BCTN	Arrow	REACT_163922 (Reactome)
BCTN			REACT_163642 (Reactome)
BCTN			REACT_163770 (Reactome)
BTD		mim-catalysis	REACT_163642 (Reactome)
	Btn-ACACA,B:2Mn2+	Arrow	REACT_163738 (Reactome)
Btn-ACACA,B:2Mn2+			REACT_163922 (Reactome)
	Btn	Arrow	REACT_11142 (Reactome)
	Btn	Arrow	REACT_163642 (Reactome)
Btn			REACT_11142 (Reactome)
Btn			REACT_163633 (Reactome)
Btn			REACT_163738 (Reactome)
Btn			REACT_163795 (Reactome)
Btn			REACT_163950 (Reactome)
	CD320	Arrow	REACT_163909 (Reactome)
CD320			REACT_163657 (Reactome)
CD320		mim-catalysis	REACT_163657 (Reactome)
CNCbl			REACT_163751 (Reactome)
	CO2	Arrow	REACT_11092 (Reactome)
	CO2	Arrow	REACT_11231 (Reactome)
COASY		mim-catalysis	REACT_11093 (Reactome)
COASY		mim-catalysis	REACT_11222 (Reactome)
	CUBN:AMN:GIF:Cbl	Arrow	REACT_163741 (Reactome)
CUBN:AMN:GIF:Cbl			REACT_163861 (Reactome)
	CUBN:AMN	Arrow	REACT_163861 (Reactome)
CUBN:AMN			REACT_163741 (Reactome)
	CYB5A:ferriheme	Arrow	REACT_11100 (Reactome)
CYB5A:ferriheme			REACT_11182 (Reactome)
	CYB5A:heme	Arrow	REACT_11182 (Reactome)
CYB5A:heme			REACT_11100 (Reactome)
CYB5A:heme		mim-catalysis	REACT_11100 (Reactome)
CYB5R3:FAD		mim-catalysis	REACT_11182 (Reactome)
	Cbl	Arrow	REACT_163656 (Reactome)
	Cbl	Arrow	REACT_163806 (Reactome)
	Cbl	Arrow	REACT_163846 (Reactome)
	Cbl	Arrow	REACT_163887 (Reactome)
	Cbl	Arrow	REACT_163923 (Reactome)
Cbl			REACT_163637 (Reactome)
Cbl			REACT_163745 (Reactome)
Cbl			REACT_163806 (Reactome)
Cbl			REACT_163887 (Reactome)
Cbl			REACT_163944 (Reactome)
Cbl			REACT_164003 (Reactome)
	CoA-SH	Arrow	REACT_11093 (Reactome)
	CoA-SH	Arrow	REACT_11209 (Reactome)
CoA-SH			REACT_11175 (Reactome)
CoA-SH			REACT_11209 (Reactome)
Cys			REACT_11112 (Reactome)
Cys			REACT_24937 (Reactome)
Cys			REACT_25122 (Reactome)
	DA-NAD+	Arrow	REACT_11116 (Reactome)
	DA-NAD+	Arrow	REACT_11196 (Reactome)
	DA-NAD+	Arrow	REACT_11237 (Reactome)
DA-NAD+			REACT_11135 (Reactome)
	DHF	Arrow	REACT_11204 (Reactome)
DHF			REACT_11170 (Reactome)
DHFR		mim-catalysis	REACT_11170 (Reactome)
DHFR		mim-catalysis	REACT_11204 (Reactome)
	DHvitC	Arrow	REACT_11168 (Reactome)
DHvitC			REACT_11095 (Reactome)
DHvitC			REACT_11168 (Reactome)
	DP-CoA	Arrow	REACT_11222 (Reactome)
DP-CoA			REACT_11093 (Reactome)
	FAD	Arrow	REACT_11128 (Reactome)
FAD			REACT_11150 (Reactome)
FAD		TBar	REACT_163635 (Reactome)
FASN			REACT_11175 (Reactome)
FLAD1		mim-catalysis	REACT_11128 (Reactome)
	FMN	Arrow	REACT_11150 (Reactome)
	FMN	Arrow	REACT_11232 (Reactome)
FMN			REACT_11128 (Reactome)
FMN			REACT_11171 (Reactome)
FMN		TBar	REACT_163635 (Reactome)
	FOLA	Arrow	REACT_11104 (Reactome)
	FOLA	Arrow	REACT_11190 (Reactome)
FOLA			REACT_11104 (Reactome)
FOLA			REACT_11190 (Reactome)
FOLA			REACT_11204 (Reactome)
FPGS-1		mim-catalysis	REACT_11134 (Reactome)
FPGS-2		mim-catalysis	REACT_11083 (Reactome)
FPGS-2		mim-catalysis	REACT_11098 (Reactome)
Food proteins:Cbl			REACT_163895 (Reactome)
	Food proteins	Arrow	REACT_163895 (Reactome)
	GIF:Cbl	Arrow	REACT_163686 (Reactome)
	GIF:Cbl	Arrow	REACT_163745 (Reactome)
	GIF:Cbl	Arrow	REACT_163861 (Reactome)
GIF:Cbl			REACT_163686 (Reactome)
GIF:Cbl			REACT_163741 (Reactome)
GIF:Cbl			REACT_163846 (Reactome)
GIF			REACT_163745 (Reactome)
GLUT1,3		mim-catalysis	REACT_11168 (Reactome)
GSH			REACT_11095 (Reactome)
	GSSG	Arrow	REACT_11095 (Reactome)
GTP			REACT_25068 (Reactome)
Glu			REACT_11134 (Reactome)
	Gly	Arrow	REACT_11159 (Reactome)
Gly			REACT_11108 (Reactome)
	H+	Arrow	REACT_11192 (Reactome)
	H+	Arrow	REACT_163830 (Reactome)
	H+	Arrow	REACT_25353 (Reactome)
H+			REACT_11092 (Reactome)
H+			REACT_11102 (Reactome)
H+			REACT_11132 (Reactome)
H+			REACT_11170 (Reactome)
H+			REACT_11182 (Reactome)
H+			REACT_11187 (Reactome)
H+			REACT_11204 (Reactome)
H+			REACT_163751 (Reactome)
H+			REACT_163988 (Reactome)
H+			REACT_164003 (Reactome)
	H2O2	Arrow	REACT_163723 (Reactome)
	H2O2	Arrow	REACT_25127 (Reactome)
	H2O2	Arrow	REACT_25348 (Reactome)
	H2O	Arrow	REACT_11205 (Reactome)
	H2O	Arrow	REACT_11211 (Reactome)
H2O			REACT_11074 (Reactome)
H2O			REACT_11135 (Reactome)
H2O			REACT_11136 (Reactome)
H2O			REACT_11150 (Reactome)
H2O			REACT_11171 (Reactome)
H2O			REACT_163723 (Reactome)
H2O			REACT_163806 (Reactome)
H2O			REACT_25050 (Reactome)
H2O			REACT_25068 (Reactome)
H2O			REACT_25127 (Reactome)
H2O			REACT_25137 (Reactome)
H2O			REACT_25353 (Reactome)
	HCN	Arrow	REACT_163751 (Reactome)
HCOOH			REACT_11109 (Reactome)
HCYS			REACT_6739 (Reactome)
HLCS		mim-catalysis	REACT_163633 (Reactome)
HLCS		mim-catalysis	REACT_163738 (Reactome)
HLCS		mim-catalysis	REACT_163795 (Reactome)
HLCS		mim-catalysis	REACT_163950 (Reactome)
	L-Ala	Arrow	REACT_24937 (Reactome)
	L-Ala	Arrow	REACT_25122 (Reactome)
L-Gln			REACT_11135 (Reactome)
	L-Glu	Arrow	REACT_11135 (Reactome)
L-Glu			REACT_11083 (Reactome)
L-Glu			REACT_11098 (Reactome)
	L-Lys	Arrow	REACT_163642 (Reactome)
L-MM-CoA			REACT_19 (Reactome)
	L-Met	Arrow	REACT_25068 (Reactome)
	L-Met	Arrow	REACT_6739 (Reactome)
	L-Ser	Arrow	REACT_11108 (Reactome)
L-Ser			REACT_11159 (Reactome)
LMBRD1		mim-catalysis	REACT_163887 (Reactome)
MDASC			REACT_11100 (Reactome)
	MMACHC:B12r	Arrow	REACT_163751 (Reactome)
	MMACHC:B12r	Arrow	REACT_164003 (Reactome)
MMACHC:B12r			REACT_163784 (Reactome)
	MMACHC:MMADHC:B12r	Arrow	REACT_163784 (Reactome)
MMACHC:MMADHC:B12r			REACT_163697 (Reactome)
MMACHC:MMADHC:B12r			REACT_163721 (Reactome)
	MMACHC:MMADHC	Arrow	REACT_163697 (Reactome)
	MMACHC:MMADHC	Arrow	REACT_163721 (Reactome)
MMACHC			REACT_163751 (Reactome)
MMACHC			REACT_164003 (Reactome)
MMACHC		mim-catalysis	REACT_163751 (Reactome)
MMACHC		mim-catalysis	REACT_164003 (Reactome)
MMADHC			REACT_163784 (Reactome)
MOCOS:PXLP		mim-catalysis	REACT_25122 (Reactome)
MOCS2			REACT_25006 (Reactome)
	MOCS3-S-S(1-):Zn2+	Arrow	REACT_24937 (Reactome)
MOCS3-S-S(1-):Zn2+			REACT_25006 (Reactome)
MOCS3-S-S(1-):Zn2+		mim-catalysis	REACT_25006 (Reactome)
	MOCS3:Zn2+ (ox.)	Arrow	REACT_25006 (Reactome)
MOCS3:Zn2+ (red.)			REACT_24937 (Reactome)
	MPT	Arrow	REACT_25353 (Reactome)
MPT			REACT_25050 (Reactome)
	MTHF	Arrow	REACT_11162 (Reactome)
	MTHFPG	Arrow	REACT_11098 (Reactome)
	MTHFPG	Arrow	REACT_11102 (Reactome)
MTHF			REACT_11098 (Reactome)
MTHF			REACT_11162 (Reactome)
MTHF			REACT_163641 (Reactome)
	MTRR:MTR(B12r)	Arrow	REACT_163898 (Reactome)
	MTRR:MTR(B12r)	Arrow	REACT_6739 (Reactome)
MTRR:MTR(B12r)			REACT_163988 (Reactome)
MTRR:MTR(B12r)		mim-catalysis	REACT_163988 (Reactome)
	MTRR:MTR(B12s)	Arrow	REACT_163988 (Reactome)
MTRR:MTR(B12s)			REACT_163641 (Reactome)
MTRR:MTR(B12s)		mim-catalysis	REACT_163641 (Reactome)
	MTRR:MTR(MeCbl)	Arrow	REACT_163641 (Reactome)
MTRR:MTR(MeCbl)			REACT_6739 (Reactome)
MTRR:MTR(MeCbl)		mim-catalysis	REACT_6739 (Reactome)
MTRR:MTR			REACT_163898 (Reactome)
Mg2+		Arrow	REACT_11132 (Reactome)
	MoCo	Arrow	REACT_25050 (Reactome)
MoCo			REACT_25122 (Reactome)
MoO4(2-)			REACT_25050 (Reactome)
	NAD+	Arrow	REACT_11135 (Reactome)
	NAD+	Arrow	REACT_11182 (Reactome)
	NAD+	Arrow	REACT_163830 (Reactome)
NAD+			REACT_11234 (Reactome)
NADH			REACT_11182 (Reactome)
NADH			REACT_163830 (Reactome)
	NADP+	Arrow	REACT_11102 (Reactome)
	NADP+	Arrow	REACT_11170 (Reactome)
	NADP+	Arrow	REACT_11187 (Reactome)
	NADP+	Arrow	REACT_11204 (Reactome)
	NADP+	Arrow	REACT_11234 (Reactome)
	NADP+	Arrow	REACT_163751 (Reactome)
	NADP+	Arrow	REACT_163988 (Reactome)
	NADP+	Arrow	REACT_164003 (Reactome)
NADP+			REACT_11192 (Reactome)
	NADPH	Arrow	REACT_11192 (Reactome)
NADPH			REACT_11102 (Reactome)
NADPH			REACT_11170 (Reactome)
NADPH			REACT_11187 (Reactome)
NADPH			REACT_11204 (Reactome)
NADPH			REACT_163751 (Reactome)
NADPH			REACT_163988 (Reactome)
NADPH			REACT_164003 (Reactome)
NADSYN1 homohexamer		mim-catalysis	REACT_11135 (Reactome)
NAMD		mim-catalysis	REACT_11136 (Reactome)
NAMPT		mim-catalysis	REACT_11225 (Reactome)
NAM			REACT_11136 (Reactome)
NAM			REACT_11225 (Reactome)
	NCA	Arrow	REACT_11136 (Reactome)
NCA			REACT_11132 (Reactome)
	NH3	Arrow	REACT_11136 (Reactome)
	NH4+	Arrow	REACT_25127 (Reactome)
NMNAT2 (Mg2+)		mim-catalysis	REACT_11116 (Reactome)
	Na+	Arrow	REACT_11072 (Reactome)
	Na+	Arrow	REACT_11120 (Reactome)
	Na+	Arrow	REACT_11142 (Reactome)
Na+			REACT_11072 (Reactome)
Na+			REACT_11120 (Reactome)
Na+			REACT_11142 (Reactome)
	Nicotinate D-ribonucleotide	Arrow	REACT_11092 (Reactome)
	Nicotinate D-ribonucleotide	Arrow	REACT_11132 (Reactome)
	Nicotinate D-ribonucleotide	Arrow	REACT_11225 (Reactome)
Nicotinate D-ribonucleotide			REACT_11116 (Reactome)
Nicotinate D-ribonucleotide			REACT_11196 (Reactome)
Nicotinate D-ribonucleotide			REACT_11237 (Reactome)
	O-phosphopantetheine-L-serine-FASN	Arrow	REACT_11175 (Reactome)
O2			REACT_163723 (Reactome)
O2			REACT_25127 (Reactome)
O2			REACT_25348 (Reactome)
PANK1/3/4		mim-catalysis	REACT_11129 (Reactome)
PANK2(111-570)		mim-catalysis	REACT_11197 (Reactome)
	PAP	Arrow	REACT_11175 (Reactome)
	PDXP	Arrow	REACT_25109 (Reactome)
PDXP			REACT_25348 (Reactome)
PDX			REACT_25109 (Reactome)
	PDXate	Arrow	REACT_163723 (Reactome)
	PPANT	Arrow	REACT_11231 (Reactome)
PPANT			REACT_11222 (Reactome)
	PPC	Arrow	REACT_11112 (Reactome)
PPC			REACT_11231 (Reactome)
	PPP	Arrow	REACT_163924 (Reactome)
	PPanK	Arrow	REACT_11129 (Reactome)
	PPanK	Arrow	REACT_11197 (Reactome)
PPanK			REACT_11112 (Reactome)
	PPi	Arrow	REACT_11092 (Reactome)
	PPi	Arrow	REACT_11112 (Reactome)
	PPi	Arrow	REACT_11116 (Reactome)
	PPi	Arrow	REACT_11128 (Reactome)
	PPi	Arrow	REACT_11132 (Reactome)
	PPi	Arrow	REACT_11135 (Reactome)
	PPi	Arrow	REACT_11196 (Reactome)
	PPi	Arrow	REACT_11222 (Reactome)
	PPi	Arrow	REACT_11225 (Reactome)
	PPi	Arrow	REACT_11237 (Reactome)
	PPi	Arrow	REACT_163633 (Reactome)
	PPi	Arrow	REACT_163738 (Reactome)
	PPi	Arrow	REACT_163795 (Reactome)
	PPi	Arrow	REACT_163950 (Reactome)
	PPi	Arrow	REACT_25006 (Reactome)
	PPi	Arrow	REACT_25050 (Reactome)
	PPi	Arrow	REACT_25068 (Reactome)
PRPP			REACT_11092 (Reactome)
PRPP			REACT_11132 (Reactome)
PRPP			REACT_11225 (Reactome)
PRSS1,3,CTRB1,2		mim-catalysis	REACT_163923 (Reactome)
	PXAP	Arrow	REACT_25323 (Reactome)
PXAP			REACT_25127 (Reactome)
PXA			REACT_25323 (Reactome)
	PXLP	Arrow	REACT_25127 (Reactome)
	PXLP	Arrow	REACT_25295 (Reactome)
	PXLP	Arrow	REACT_25348 (Reactome)
PXL			REACT_163723 (Reactome)
PXL			REACT_25295 (Reactome)
	PanK	Arrow	REACT_11072 (Reactome)
PanK			REACT_11072 (Reactome)
PanK			REACT_11129 (Reactome)
PanK			REACT_11197 (Reactome)
	Pi	Arrow	REACT_11083 (Reactome)
	Pi	Arrow	REACT_11098 (Reactome)
	Pi	Arrow	REACT_11109 (Reactome)
	Pi	Arrow	REACT_11134 (Reactome)
	Pi	Arrow	REACT_11171 (Reactome)
	Pi	Arrow	REACT_163806 (Reactome)
	Pi	Arrow	REACT_25137 (Reactome)
	Precursor Z	Arrow	REACT_25068 (Reactome)
Precursor Z			REACT_25353 (Reactome)
QPRT		mim-catalysis	REACT_11092 (Reactome)
	QUIN	Arrow	REACT_11211 (Reactome)
QUIN			REACT_11092 (Reactome)
			REACT_11072 (Reactome)	The plasma membrane-associated transport protein SLC5A6 (SMVT) mediates the uptake of one molecule of pantothenate (PanK) and two sodium ions from the extracellular space to the cytosol. Limited Northern blotting studies suggest that SLC5A6 is widely expressed, and abundant in placenta and small intestine. SLC5A6 may thus play a central role in pantothenate uptake. SLC5A6 also mediates the uptake of biotin and lipoate (Prasad et al. 1999; Wang et al. 1999).
			REACT_11074 (Reactome)	The methenyltetrahydrofolate cyclohydrolase activity of the trifunctional MTHFD1 enzyme catalyzes the reversible reaction of 5,10-methenylTHF polyglutamate and H2O to form 10-formylTHF polyglutamate. MTHFD1 is cytosolic and occurs as a dimer. The human enzyme has been identified and partially characterized biochemically (Hum et al. 1988); additional reaction details can be inferred from the properties of the well-studied homologous rabbit enzyme (Villar et al. 1985).
			REACT_11081 (Reactome)	Two transport proteins, SLC19A2 (THTR1) and SLC19A3 (THTR2), associated with the plasma membrane, are each able to mediate the transport of extracellular thiamin into the cytosol. In the body, both transporters are widely distributed, and both are abundant in kidney and intestinal epithelia, consistent with their involvement in thiamin uptake under physiological conditions (Ashokkumar et al. 2006; Said et al. 2004; Subramanian et al. 2006 - J Biol Chem). The observation that mutations in SLC19A2 (THTR1) cause a progressive disorder that can be partially reversed by treatment with high doses of thiamin likewise suggests a role for this protein in thiamin uptake under normal conditions (Diaz et al. 1999; Fleming et al. 1999; Labay et al. 1999). Two features of this transport process remain incompletely understood, however. First, mutations in SLC19A3 cause a progressive disorder that is responsive to biotin treatment (Zhou et al. 2005), although studies of cultured cells indicate that the protein has no affinity for biotin (Subramanian et al. 2006 - Am J Physiol). Also, studies to date provide little information about the mechanism by which thiamin, once taken up by epithelial cells in the intestine and kidney, is released from these cells into the blood.
			REACT_11083 (Reactome)	Cytosolic folylpolyglutamate synthase catalyzes the reaction of THF-glutamate(n), L-glutamate, and ATP to form THF-glutamate(n+1), ADP, and orthophosphate. (The first glutamate residue is attached to the glutamate moiety of THF itself; for convenience the process is annotated here as if it proceeded in a single concerted step.) The extent of conjugation is variable, but the commonest cytosolic form of THF has five added glutamate residues. Although its properties as a donor of one-carbon units are not affected by glutamate addition, THF that lacks added glutamate residues cannot be retained in the cytosol so this reaction is needed for normal THF function under physiological conditions (Garrow et al. 1992; Chen et al. 1996).
			REACT_11092 (Reactome)	The enzyme, nicotinate nucleotide pyrophosphorylase, is specific for quinolinate. Its activity is strictly dependent on Mg2+ ions being present. A phosphoribosyl group is transferred to quinolinate to form nicotinate D-ribonucleotide. This reaction represents another rate-limiting step of the pathway from tryptophan to NAD+.
			REACT_11093 (Reactome)	The kinase activity of CoA synthase (COASY) catalyzes the phosphorylation of dephospho-CoA to form Coenzyme A (CoA-SH). The enzyme is located in the mitochondrial outer membrane (Daugherty et al. 2002; Zhyvoloup et al. 2003).
			REACT_11095 (Reactome)	Cytosolic omega class glutathione transferases (GSTO1 and GSTO2) catalyze the reaction of dehydroascorbate (DHvitC) and glutathione (GSH) to form ascorbate (VitC) and oxidized glutathione (GSSG). The GSTO enzymes occur as homodimers (Board et al. 2000), and while both have dehydroascorbate reductase activity in vitro, that of GSTO2 is much greater than that of GSTO1 (Schmuck et al. 2005). Polymorphisms affecting the activities of the two enzymes have been described (Whitbread et al. 2005).
			REACT_11098 (Reactome)	Cytosolic folylpolyglutamate synthase catalyzes the reaction of 5-methylTHF-glutamate(n), L-glutamate, and ATP to form 5-methylTHF-glutamate(n+1), ADP, and orthophosphate. (The first glutamate residue is attached to the glutamate moiety of 5-methylTHF itself; for convenience the process is annotated here as if it proceeded in a single concerted step.) The extent of conjugation is variable, but the commonest cytosolic form of 5-methylTHF has five added glutamate residues. Although its properties as a donor of one-carbon units are not affected by glutamate addition, 5-methylTHF that lacks added glutamate residues cannot be retained in the cytosol so this reaction is needed for normal 5-methylTHF function under physiological conditions (Garrow et al. 1992; Chen et al. 1996).
			REACT_11100 (Reactome)	The reduction of cytosolic semidehydroascorbate (SDA) to ascorbate (vitC) is catalyzed by cytochrome B5 (CYB5A) associated with the mitochondrial outer membrane. In the course of the reaction, the heme iron of the cytochrome is oxidized (Linster & Van Schaftingen 2007, Shirabe et al. 1995).
			REACT_11102 (Reactome)	Cytosolic MTHFR dimer catalyzes the reaction of 5,10-methyleneTHF polyglutamate, NADPH, and H+ to form 5-methylTHF polyglutamate and NADP+. The specificity and importance of this reaction in vivo have been established through the study of patients deficient in the enzyme (Goyette et al. 1995).
			REACT_11104 (Reactome)	SLC46A1 protein in the plasma membrane mediates the reversible transport of folate between the extracellular space and the cytosol. Retention of folate within the cell is dependent on polyglutamate addition (Qiu et al. 2006; Chen et al. 1996).
			REACT_11108 (Reactome)	Cytosolic serine hydroxymethyltransferase catalyzes the reversible reaction of 5,10-methyleneTHF polyglutamate and glycine to form tetrahydrofolate polyglutamate (THF polyglutamate) and serine. The active form of the enzyme is a tetramer (Renwick et al. 1998).
			REACT_11109 (Reactome)	The formate-tetrahydrofolate ligase activity of the trifunctional MTHFD1 enzyme catalyzes the reaction of THF polyglutamate, formate, and ATP to form 10-formylTHF polyglutamate, ADP, and orthophosphate. MTHFD1 is cytosolic and occurs as a dimer. The human enzyme has been identified and partially characterized biochemically (Hum et al. 1988); additional reaction details can be inferred from the properties of the well-studied homologous rabbit enzyme (Villar et al. 1985).
			REACT_11112 (Reactome)	The conjugation of cysteine (Cys) and 4'- phosphopantothenate (PPanK) to form 4-phosphopantothenoylcysteine (PPC) , coupled to the conversion of ATP to AMP and pyrophosphate, is catalyzed by cytosolic phosphopantothenate-cysteine ligase (PPCS aka Phosphopantothenoylcysteine synthase or PPC synthase). Mammalian PPCS prefers ATP to CTP, unlike the E. coli ortholog (Daughtery et al. 2002; Manoj et al. 2003).
			REACT_11116 (Reactome)	NMNAT2 catalyzes the reaction of nicotinate D-ribonucleotide and ATP to form deamino-NAD+ (nicotinate adenine dinucleotide) and pyrophosphate (Sorci et al. 2007). The active form of the enzyme is a monomer in vitro (Raffaelli et al. 2002). Although the predicted amino acid sequence of the enzyme lacks an obvious signal sequence or transmembrane domain (Yalowitz et al. 2004), recombinant FLAG-tagged protein expressed in HeLa cells localizes predominantly to the Golgi apparatus (Berger et al. 2005). Its localization within the Golgi apparatus is unknown and the annotation here is based on the plausible but speculative assumption that the enzyme is associated with the Gogi membrane and accessible from the cytosol. Immunostaining studies indicate that the protein is abundant in Islets of Langerhans and in several regions of the brain (Yalowitz et al. 2004).
			REACT_11120 (Reactome)	The plasma membrane-associated transport proteins SVCT1 and SVCT2 are each capable of mediating the uptake of one molecule of ascorbate (VitC) and two sodium ions from the extracellular space to the cytosol (Daruwala et al. 1999; Rajan et al. 1999; Wang et al. 1999). In the body SVCT2 is expressed in most tissues, while SVCT1 is largely confined to epithelial cells (Liang et al. 2001). SVCT2 may mediate fetal uptake of ascorbate from the maternal circulation (Rajan et al. 1999). The transporters responsible for its uptake from the small intestine and for its release from enterocytes into the circulation have not been identified, although both SVCT1 and 2 are expressed in intestinal cells.
			REACT_11128 (Reactome)	FMN can be phosphorylated and adenylated to produce the second cofactor from riboflavin origins, flavin adenine dinucleotide (FAD). The enzyme responsible , FMN adenylyltransferase (FLAD1 aka FAD synthase), is cytosolic and transfers a phosphate and an adenyl group from ATP to form FAD.
			REACT_11129 (Reactome)	Cytosolic pantothenate kinases catalyze the reaction of ATP and pantothenate to form ADP and phosphopantothenate. This enzymatic activity has been demonstrated in crude cell extracts for two isoforms of mouse pantothenate kinase 1 (Rock et al. 2002) and for their human homologues (Ramaswamy and 2004). Two additional human genes, PANK3 and PANK4, encode closely related proteins but pantothenate kinase activity has not been demonstrated experimentally for them (Leonardi et al. 2005; Zhou et al. 2001).
			REACT_11132 (Reactome)	Cytosolic nicotinate phosphoribosyltransferase (NaPRT) catalyzes the Mg++-dependent reaction of nicotinate and phosphoribosyl pyrophosphate to form nicotinate mononucleotide (NaMN, nicotinate D-ribonucleotide) and pyrophosphate. The active form of the enzyme is a homodimer (Preiss and Handler 1958; Niedel and Dietrich 1973; Hara et al. 2007).
			REACT_11134 (Reactome)	Mitochondrial folylpolyglutamate synthase catalyzes the reaction of THF-glutamate(n), L-glutamate, and ATP to form THF-glutamate(n+1), ADP, and orthophosphate. (The first glutamate residue is attached to the glutamate moiety of THF itself; for convenience the process is annotated here as if it proceeded in a single concerted step.) The extent of conjugation is variable, but the commonest mitochondrial form of THF has six added glutamate residues. Although its properties as a donor of one-carbon units are not affected by glutamate addition, THF that lacks added glutamate residues cannot be retained in the mitochondrial matrix so this reaction is needed for normal THF function under physiological conditions. The mitochondrial and cytosolic forms of folylpolyglutamate synthase are encoded by the same gene - alternative splicing generates mRNA with or without an initial exon encoding a mitochondrial targeting sequence (Garrow et al. 1992; Chen et al. 1996).
			REACT_11135 (Reactome)	NAD synthase catalyzes the final step in the biosynthesis of NAD+, both in the de novo synthesis and in the salvage pathways. The enzyme makes use of glutamine as an amide donor in the reaction. NAD synthase exists as a homohexamer in the cytosol. There are two forms of NAD synthase in humans, NADsyn1 and NADsyn2. The major difference between the two forms is that NADsyn1 appears to be glutamine-dependent whereas NADsyn2 is strictly ammonia-dependent.
			REACT_11136 (Reactome)	Nicotinamide deaminase (NAMD) deaminates nicotinamide to nicotinate. There is no literature on the human enzyme but there is evidence showing a marked nicotinamide deaminase activity when red blood cells are infected with Plasmodium falciparum (Zerez C. et al, 1990). What is not clear is whether this activity is stimulated by the parasite or encoded by its genome.
			REACT_11142 (Reactome)	The plasma membrane-associated transport protein SLC5A6 (aka sodium-dependent multivitamin transporter, SMVT) mediates the uptake of one molecule of biotin (Btn) and two sodium ions from the extracellular space to the cytosol. Limited Northern blotting studies suggest that SLC5A6 is widely expressed and abundant in placenta, liver and small intestine. SLC5A6 may thus play a central role in Btn uptake from dietary sources. SLC5A6 also mediates the uptake of pantothenate and lipoate (Prasad et al. 1999; Wang et al. 1999, Balamurugan et al. 2003).
			REACT_11143 (Reactome)	SLC25A32 protein in the inner mitochondrial membrane mediates the reversible transport of tetrahydrofolate between the cytosol and the mitochondrial matrix. Retention of tetrahydrofolate within the mitochondrial matrix is dependent on mitochondrial polyglutamate addition (Titus and Moran 2000; Chen et al. 1996).
			REACT_11150 (Reactome)	Phosphatase action on flavin adenine dinucleotide (FAD) can reform flavin mononucleotide (FMN). The enzyme performing the reaction is nucleotide pyrophosphatase (ENPP1) and it exists as a homodimer on the plasma membrane.
			REACT_11159 (Reactome)	Cytosolic serine hydroxymethyltransferase catalyzes the reversible reaction of tetrahydrofolate polyglutamate (THF polyglutamate) and serine to form 5,10-methyleneTHF polyglutamate and glycine. The active form of the enzyme is a tetramer (Renwick et al. 1998). In the body, this reaction is a major source of 5,10-methyleneTHF, which in turn is a critical precursor in the synthesis of dTMP.
			REACT_11162 (Reactome)	SLC19A1 protein, associated with the plasma membrane, mediates the uptake of extracellular 5-methyltetrahydrofolate and other reduced folates (Williams and Flintoff 1995; Ferguson and Flintoff 1999).
			REACT_11168 (Reactome)	The uptake of extracellular dehydroascorbate into the cytosol is mediated by GLUT1 and GLUT3 associated with the plasma membrane (Rumsey et al. 1997, 2000). This process may play a significant role in ascorbate utilization in the central nervous system (Agus et al. 1997). The process is efficiently competitively inhibited by glucose, leading to the suggestion that inhibited dehydroascorbate uptake may contribute to the pathology of diabetes (Liang et al. 2001; Rumsey et al. 2000).
			REACT_11170 (Reactome)	Cytosolic dihydrofolate reductase catalyzes the reaction of dihydrofolate, NADPH, and H+ to form tetrahydrofolate (THF) and NADP+ (Chen et al. 1984; Davies et al. 1990).
			REACT_11171 (Reactome)	Cytosolic, homodimeric tartrate-resistant acid phosphatase type 5 (TRAP) catalyzes the hydrolysis of flavin mononucleotide (FMN) to yield riboflavin (RIB) and orthophosphate.
			REACT_11175 (Reactome)	Cytosolic AASDHPPT (alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase) catalyzes the transfer of a phosphopantetheine moiety from coenzyme A to serine 2156 within the ACP domain of FAS (fatty acyl synthase). Only a single human enzyme with phosphopantetheinyl transferase activity has been identified, and its broad substrate specificity suggests that it may be responsible as well for the postranslational modification of enzymes of lysine catabolism (Joshi et al. 2003; Praphanphoj et al. 2001).
			REACT_11182 (Reactome)	Cytochrome b5 reductase (CYB5R3) catalyzes the reduction of cytosolic ferric CYB5A (CYB5A:ferriheme) to ferrous CYPB5A (CYB5A:heme), coupled to the conversion of NADH to NAD+ (Shirabe et al. 1995). CYB5R3 is associated with the outer mitochondrial membrane via a myristoyl group added post-translationally to glycine residue 2 of the protein (Borgese et al. 1993).
			REACT_11187 (Reactome)	The methylenetetrahydrofolate dehydrogenase activity of the trifunctional MTHFD1 enzyme catalyzes the reversible reaction of 5,10-methenylTHF polyglutamate, NADPH, and H+ to form 5,10-methyleneTHF polyglutamate and NADP+. MTHFD1 is cytosolic and occurs as a dimer. The human enzyme has been identified and partially characterized biochemically (Hum et al. 1988); additional reaction details can be inferred from the properties of the well-studied homologous rabbit enzyme (Villar et al. 1985).
			REACT_11190 (Reactome)	SLC46A1 protein in the plasma membrane mediates the reversible transport of folate between the extracellular space and the cytosol. Retention of folate within the cell is dependent on polyglutamate addition. Although the SLC46A1 gene is expressed in several tissues in the body, this transporter appears to be primarily needed for absorption of dietary folate from the intestinal lumen (Qiu et al. 2006; Chen et al. 1996).
			REACT_11192 (Reactome)	The methylenetetrahydrofolate dehydrogenase activity of the trifunctional MTHFD1 enzyme catalyzes the reversible reaction of 5,10-methyleneTHF polyglutamate and NADP+ to form 5,10-methenylTHF polyglutamate, NADPH, and H+. MTHFD1 is cytosolic and occurs as a dimer. The human enzyme has been identified and partially characterized biochemically (Hum et al. 1988); additional reaction details can be inferred from the properties of the well-studied homologous rabbit enzyme (Villar et al. 1985).
			REACT_11196 (Reactome)	NMNAT3 catalyzes the reaction of nicotinate D-ribonucleotide and ATP to form deamino-NAD+ (nicotinate adenine dinucleotide) and pyrophosphate (Sorci et al. 2007). The active form of the enzyme is a tetramer in vitro (Zhang et al. 2003). Recombinant FLAG-tagged protein expressed in HeLa cells localizes both to the cytosol and to mitochondria (Berger et al. 2005). The cytosolic protein is annotated here.
			REACT_11197 (Reactome)	Pantothenate kinase 2 catalyzes the reaction of ATP and pantothenate to form ADP and phosphopantothenate. While pantothenate kinase 2 co-purifies with mitocondria, its precise location within the mitochondrion has not been established (Hortnagel et al. 2003; Johnson et al. 2004). Recent work by Leonardi et al. (2007) supports a model in which the enzyme is located in the intermembrane space, hence freely accessible to small molecules from the cytosol.Pantothenate is phosphorylated by pantothenate kinase (PANK). Deficiencies in PANK2 cause a progressive neurodegenerative disorder associated with iron accumulation in the brain, but the relationship between disease symptoms and pantothenate metabolism remains unclear (Zhou et al. 2001; Zhang et al. 2006).
			REACT_11204 (Reactome)	Cytosolic dihydrofolate reductase catalyzes the reaction of folate, NADPH, and H+ to form dihydrofolate and NADP+ (Chen et al. 1984; Davies et al. 1990).
			REACT_11205 (Reactome)	The methenyltetrahydrofolate cyclohydrolase activity of the trifunctional MTHFD1 enzyme catalyzes the reversible reaction of 10-formylTHF polyglutamate to form 5,10-methenylTHF polyglutamate and H2O. MTHFD1 is cytosolic and occurs as a dimer. The human enzyme has been identified and partially characterized biochemically (Hum et al. 1988); additional reaction details can be inferred from the properties of the well-studied homologous rabbit enzyme (Villar et al. 1985).
			REACT_11209 (Reactome)	Graves disease carrier protein (SLC25A16), associated with the inner mitochondrial membrane, mediates the transport of cytosolic coenzyme A (CoA-SH) into the mitochondrial matrix. Evidence for this event is indirect. The protein has the sequence motifs expected for a transport protein, and yeast cells deficient in its homologue, Leu5p, fail to accumulate mitochondrial CoA-SH and can be rescued by expression of SLC25A16. At the same time, neither the yeast nor the human protein has been shown directly to function as a transporter (Prohl et al. 2001, Leonardi et al. 2007).
			REACT_11211 (Reactome)	Cytosolic 2-amino 3-carboxymuconate semialdehyde reacts non-enzymatically to form quinolinate and water (Fukuoka et al. 1998).
			REACT_11219 (Reactome)	SLC25A32 protein in the inner mitochondrial membrane mediates the reversible transport of tetrahydrofolate between the cytosol and the mitochondrial matrix. Retention of tetrahydrofolate within the mitochondrial matrix is dependent on mitochondrial polyglutamate addition (Titus and Moran 2000; Chen et al. 1996).
			REACT_11222 (Reactome)	The adenylyl transferase activity of bifunctional coenzyme A synthase (COASY) catalyzes the transfer of an adenylyl group from ATP to pantetheinephosphate (PPANT) to form dephospho-Coenzyme A (DP-CoA) (Daugherty et al. 2002). The enzyme is associated with the mitochondrial outer membrane (Zhyvoloup et al. 2003).
			REACT_11225 (Reactome)	Nicotinamide phosphoribosyltransferase (NamPRT) catalyzes the condensation of nicotinamide with 5- phosphoribosyl-1-pyrophosphate to yield nicotinamide D-ribonucleotide (NMN), an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway.
			REACT_11231 (Reactome)	The decarboxylation of phosphopantothenoylcysteine (PPC) to 4'-phosphopantetheine (PPANT) is carried out by phosphopantothenoylcysteine decarboxylase (PPCDC). PPCDC is cytosolic and exists as a homotrimer, binding one FMN cofactor per subunit. While a second isoform has been inferred from large-scale sequnceing studies, it lacks the protein's FMN-binding domain and would thus appear to be nonfunctional if it is expressed.
			REACT_11232 (Reactome)	Phosphorylation of riboflavin (RIB) results in the formation of the first cofactor, flavin mononucleotide (FMN). This reaction is catalyzed by riboflavin kinase (RFK), a cytosolic enzyme existing as a monomer. It utilizes either zinc or magnesium ions in the reaction.
			REACT_11233 (Reactome)	Cytosolic thiamin pyrophosphokinase (TPK1) catalyzes the reaction of thiamin (THMN) and ATP to form thiamin diphosphate (ThDP aka thiamin pyrophosphate) and ADP. ThDP is an active cofactor for transketolase, pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, enzymes involved in glycolysis and energy production. The gene encoding the human enzyme has been cloned and its protein product has been shown to have TPK1 activity (Nosaka et al. 2001; Zhao et al. 2001). Its homodomeric structure and association with Mg2+ are inferred from properties of the homologous yeast enzyme (Baker et al. 2001).
			REACT_11234 (Reactome)	NAD+ kinase catalyzes the transfer of a phosphate group from ATP to NAD+, forming NADP+. This is the only way to generate NADP+ in all living organisms. The enzyme requires a divalent metal to be effective. Zn2+ is the best metal for this purpose.
			REACT_11237 (Reactome)	NMNAT1 catalyzes the reaction of nicotinate D-ribonucleotide and ATP to form deamino-NAD+ (nicotinate adenine dinucleotide) and pyrophosphate (Schweiger et al. 2001). The active form of the enzyme in vitro is a hexamer (Zhou et al. 2002), and its activity is substantially greater in the presence of Zn++ than of Mg++ (Sorci et al. 2007). The predicted amino acid sequence of the enzyme contains a nuclear localization domain and the protein is observed to localize to the nucleus (Schweiger et al. 2001; Berger et al. 2005).
			REACT_163633 (Reactome)	Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. In the cytosol, these apo carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Propionyl-CoA carboxylase is most likely functional as a dodecamer, composed of six Btn-containing alpha subunits (PCCA) and six beta subunits (PCCB). The exact order in which this complex is constructed is unknown.
			REACT_163635 (Reactome)	Solute carrier family 52, riboflavin transporter, member 3 (SLC52A3) transports riboflavin (RIB) from the lumen into small intestine epithelial cells (Yao et al. 2010). Activity is inhibited by riboflavin analogues such as flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) (Yao et al. 2010). Defects in SLC52A3 cause Brown-Vialetto-Van Laere syndrome type 1 (BVVLS1; MIM:211530). BVVLS1 is a rare autosomal recessive neurologic disorder characterized by sensorineural hearing loss and a variety of cranial nerve palsies (Green et al. 2010). Defects in SLC52A3 also cause Fazio-Londe disease (FALOND; MIM:211500), a rare neurological disease characterized by progressive weakness of the muscles innervated by cranial nerves located at the lower brain stem (Bosch et al. 2011).
			REACT_163637 (Reactome)	Transcobalamin (TCN) is a vitamin B12-binding protein secreted by endothelial cells into plasma that facilitates the transport of cobalamin (Cbl, vitamin B12) into hepatocytes or cells requiring Cbl. Two TCN genes, TCN1 (aka haptocorrin) and TCN2, code for functional proteins that can bind Cbl (Johnston et al. 1989, Quadros et al. 1986, Wuerges et al. 2006). TCN2 can be bound to between 10-30% of the total circulating Cbl, the remaining Cbl bound to TCN1. TCN2 transports Cbl used by tissues. The role of TCN1 carrying between 70-90% of the Cbl serum fraction is unknown.
			REACT_163641 (Reactome)	Methionine synthase (MTR) catalyses the transfer of a methyl group from 5-methyltetrahydrofolate (MTHF) to homocysteine (HCYS) to then form methionine (L-Met). In the first step, MTR mediates the transfer of a methyl group from 5-methyltetrahydrofolate (MTHF) to B12s (bound to the enzyme MTR) to form the cofactor methylcobalamin (MeCbl), the form that activates MTR (Leclerc et al. 1996). Defects in MTR cause methylcobalamin deficiency type G (cblG; MIM:250940), an autosomal recessive inherited disease that causes mental retardation, macrocytic anemia, and homocystinuria. Mutations causing cblG include P1173L, Ile881, H920D, R585*, E1204* and A1204P (Leclerc et al. 1996, Gulati et al. 1996, Watkins et al. 2002).
			REACT_163642 (Reactome)	Human biotinidase (BTD) (Cole et al. 1994) is a secreted enzyme that catalyzes the hydrolysis of biocytin (BCTN), the product of biotin-dependent carboxylase degradation, to biotin (Btn) and lysine. BTD deficiency, an autosomal recessive disorder, results in a secondary Btn deficiency that leads to late-onset multiple carboxylase deficiency (MIM:253260) (Wolf et al. 1983).
			REACT_163656 (Reactome)	Once in the lysosome, transcobalamin 2:cobalamin (TCN2:Cbl) is degraded to release Cbl (Youngdahl-Turner et al. 1979). Cbl is ready to be exported out of the lysosome to the cytosol by the probable lysosomal cobalamin transporter (LMBRD1) (Rutsch et al. 2009). Once in the cytosol, Cbl can be used in the synthesis of the essential cofactors methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) as described in the steps above.
			REACT_163657 (Reactome)	The ubiquitously-expressed CD320 antigen (CD320 aka transcobalamin receptor, TCblR) internalises TCN2:Cbl by endocytosis after binding to it (Quadros et al. 2009, Quadros et al. 2005). Defects in CD320 cause methylmalonic aciduria type TCblR (MMATC aka methylmalonic aciduria; MIM:613646) (Quadros et al. 2010).
			REACT_163686 (Reactome)	Gastric intrinsic factor (GIF) bound to cobalamin (Cbl) is targeted to lysosomes for degradation (Fyfe et al. 2004).
			REACT_163697 (Reactome)	Methylmalonic aciduria and homocystinuria type D protein (MMADHC) has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence which is thought to target cob(II)alamin (B12r) to the mitochondria (Stucki et al. 2012, Coelho et al. 2008). The actual mechanism of transport into the mitochondrion is unknown.
			REACT_163704 (Reactome)	Once biotinylated, three halocarboxylases (hCBXs) are localised to the mitochondrial matrix. The mechanism of transfer is still unclear. Pyruvate carboxylase (PC) is required for gluconeogenesis, lipogenesis, neurotransmitter synthesis and insulin secretion; Methylcrotonyl-CoA carboxylase (MCC) is required for amino acid metabolism; propionyl-CoA carboxylase (PCC) is required for odd-chain fatty acid oxidation (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010).
			REACT_163721 (Reactome)	Exact details are unclear but it is assumed once the binding proteins (MMADCHC and MMADHC) deliver B12r to its cytosolic destination, they dissociate from B12r (Mah et al. 2013, Plesa et al. 2011, Deme et al. 2012).
			REACT_163723 (Reactome)	Aldehyde oxidase (AOX1) is a complex molybdo-flavoprotein that belongs to the xanthine oxidase family. It is active as a homodimer, with each monomer binding two distinct [2Fe2S] clusters, FAD and the molybdenum cofactor. AOX1 plays an important role in the metabolism of drugs based on its broad substrate specificity oxidising aromatic aza-heterocycles and aldehydes (Hartmann et al. 2012).
			REACT_163738 (Reactome)	Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. In the cytosol, these apo carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Acetyl-CoA carboxylases 1 and 2 (ACACA and ACACB) bind 2 Mn2+ and 1 Btn per subunit (Colbert et al. 2010). They can exist as either monomers, homodimers or homotetramers (latter two not shown in this reaction) (Magnard et al. 2002, Moreau et al. 2006). Unlike the other carboxylases acted upon by HCLS, ACACA and B are located in the cytosol (shown here) as well as the mitochondrial membrane. The exact order in which this complex is constructed is unknown.
			REACT_163741 (Reactome)	In the mucosal cells of the distal ileum, in preparation for internalisation, the gastric intrinsic factor:cobalamin (GIF:Cbl) complex interacts with cubilin (CUBN). CUBN is a cotransporter facilitating uptake of lipoproteins, vitamins and iron (Matthews et al. 2007). CUBN is in complex with protein amnionless (AMN), a necessary component which directs subcellular localization and endocytosis of GIF:Cbl (Fyfe et al. 2004, Anderson et al. 2010). Defects in CUBN and AMN both cause recessive hereditary megaloblastic anemia 1 (RH-MGA1 aka MGA1 Norwegian type or Imerslund-Grasbeck syndrome, I-GS; MIM:261100). The resultant malabsorption of Cbl (vitamin B12) leads to impaired B12-dependent folate metabolism and ultimately impaired thymine synthesis and DNA replication (Aminoff et al. 1999, Kristiansen et al. 2000, Tanner et al. 2003, Densupsoontorn et al. 2012).
			REACT_163745 (Reactome)	Gastric parietal cells secrete gastric intrinsic factor (GIF) which binds tightly to free cobalamin (Cbl) released from transcobalamin (TCN1, haptocorrin) in the proximal intestine (Matthews et al. 2007). Cbl must bind to GIF to be absorbed from the small intestine.
			REACT_163751 (Reactome)	A semi-synthetic form of the vitamin, cyanocobalamin (CNCbl, where a cyanide group is in the upper axial position), is produced from bacterial hydroxocobalamin and used in many pharmaceuticals, supplements and as a food additive. It is presumed to take the same route after ingestion as cobalamin (Cbl) (Randaccio et al. 2010). At this point in the pathway, CNCbl is reductively decyanated by methylmalonic aciduria and homocystinuria type C protein (MMACHC) to produce cob(II)alamin (B12r, vitaman B12r) and hydrogen cyanide (HCN) (Kim et al. 2008). Decyanation of CNCbl is required for it to be made available for conversion to active cofactors.
			REACT_163761 (Reactome)	Transcobalamin 2 (TCN2) degradation is necessary for cobalamin (Cbl) to be released from the complex and made available for binding to Cbl-dependant apoenzymes (Youngdahl-Turner et al. 1979). The TCN2:Cbl complex translocates to lysosomes for degradation.
			REACT_163770 (Reactome)	After holocarboxylase degradation, biocytin (BCTN) translocates to the extracellular region by an unknown mechanism (Chandler & Ballard 1985).
			REACT_163784 (Reactome)	MMACHC:B12r (cob(II)alamin, vitamin B12r) binding to methylmalonic aciduria and homocystinuria type D protein (MMADHC) represents a branch point in the targeted delivery of B12r to either cytosolic or mitochondrial enzymes requiring this cofactor (Mah et al. 2013, Plesa et al. 2011, Deme et al. 2012). Both MMACHC and MMADHC are implicated in the intracellular transport of cobalamins but exact details of the mechanisms involved remain unclear. Defects in MMADHC cause methylmalonic aciduria and homocystinuria type cblD (MMAHCD; MIM:277410), a disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) (Coelho et al. 2008).
			REACT_163795 (Reactome)	Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. In the cytosol, these apo carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Methylcrotonoyl-CoA carboxylase is most likely functional as a dodecamer, composed of 6 Btn-containing alpha subunits (MCCC1) and six beta subunits (MCCC2). The exact order in which this complex is constructed is unknown.
			REACT_163806 (Reactome)	Multidrug resistance-associated protein 1 (ABCC1, MRP1) can specifically mediate the ATP-dependant export of free cobalamin (Cbl aka vitamin B12) from small intestine cells to the portal vein (Shah et al. 2011).
			REACT_163820 (Reactome)	The mitochondrial holocarboxylases (hCBXs) propionyl-CoA carboxylase, methylcrotonoyl-CoA carboxylase and pyruvate carboxylase are degraded proteolytically to biocytin (BCTN aka biotinyllysine) or small biotinyl peptides (not shown here) (Chandler & Ballard 1985, Hymes & Wolf 1996, Hymes & Wolf 1999).
			REACT_163830 (Reactome)	Mitochondrial cob(I)yrinic acid a,c-diamide adenosyltransferase (MMAB) is a dual purpose enzyme involved in the reduction and adenosylation of cobalamin. In the first step, MMAB reduces cob(II)alamin (B12r) to cob(I)alamin (B12s) (Fan & Bobik 2008, Leal et al. 2003). Defects in MMAB cause methylmalonic aciduria type cblB (MMAB aka methylmalonic aciduria type B or vitamin B12-responsive methylmalonicaciduria of cblB complementation type; MIM:251110). Affected individuals have methylmalonic aciduria and metabolic ketoacidosis, despite a functional methylmalonyl-CoA mutase. In severe cases, newborns are lethargic, prone to vomiting and fail to thrive (Dobson et al. 2002).
			REACT_163846 (Reactome)	In the lysosome, gastric intrinsic factor (GIF) bound to cobalamin (Cbl) is degraded to release Cbl (Fyfe et al. 2004).
			REACT_163861 (Reactome)	The cubilin:protein amnionless (CUBN:AMN) complex mediates the internalisation and endocytosis of gastric internal factor:cobalamin (GIF:Cbl) into mucosal cells of the distal ileum (Fyfe et al. 2004).
			REACT_163887 (Reactome)	The probable lysosomal cobalamin transporter (LMBRD1) is the most likely candidate to transport cobalamin (Cbl) from inside the lysosome to the cytosol (Rutsch et al. 2009). From here, Cbl can either be used to synthesise the essential cofactors for methionine synthase in the cytosol or methylmalonyl-CoA mutase in the mitochondria or, it can transported out of the cell to tissues that require Cbl. Defects in LMBRD1 cause methylmalonic aciduria and homocystinuria type cblF (MMAHCF; MIM:277380), characterised biochemically by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MetCbl) (Rutsch et al. 2009, Gailus et al. 2010).
			REACT_163895 (Reactome)	Transcobalamin 1 (TCN1 aka haptocorrin, HC) is a glycoprotein produced by salivary glands in response to food ingestion (Johnston et al. 1989). TCN1 binds strongly to cobalamin (Cbl aka vitamin B12) and its essential function is protection of the acid-sensitive Cbl while it moves through the stomach. Once food is in the stomach, pepsin and the acidic pH degrade food proteins. Cbl is in its +3 oxidation state in dietary sources.
			REACT_163898 (Reactome)	Methionine synthase reductase (MTRR) is involved in reducing B12r (cob(II)alamin) to B12s (cob(I)alamin), the cofactor form used by methionine synthase (MTR) to become functional. MTRR requires 1 FMN and 1 FAD per subunit for activity (Wolthers et al. 2007). MTRR exists a stable complex with MTR, bound through their FMN-binding and C-terminal activation domains respectively (Wolthers & Scrutton 2007, Wolthers & Scrutton 2009).
			REACT_163909 (Reactome)	Once the receptor complex (TCN2:Cbl:CD320) is internalised by endocytosis, the receptor (CD320) dissociates to return to the plasma membrane (Youngdahl-Turner et al. 1979).
			REACT_163922 (Reactome)	Cytosolic acetyl-CoA carboxylases 1 and 2 (Btn-ACACA/B:2Mn2+) are degraded proteolytically to biocytin (BCTN aka biotinyllysine) or small biotinyl peptides (not shown here) by an unknown protease (Chandler & Ballard 1985, Hymes & Wolf 1996, Hymes & Wolf 1999).
			REACT_163923 (Reactome)	In the proximal intestine, pancreatic enzymes degrade transcobalamin 1 (TCN1) to release cobalamin (Cbl). The two major pancreatic proteases are trypsins (PRSSs) and chymotrypsins (CTRBs) (Srikumar & Premalatha 2003, Nielsen et al. 2012).
			REACT_163924 (Reactome)	Mitochondrial cob(I)yrinic acid a,c-diamide adenosyltransferase (MMAB) is a dual purpose enzyme involved in the reduction and adenosylation of cobalamin. In the second step, MMAB transfers an adenosyl group from ATP to cob(I)alamin (B12s) to form adenosylcabalamin (AdoCbl) (Fan & Bobik 2008, Leal et al. 2003). Defects in MMAB cause methylmalonic aciduria type cblB (MMAB aka methylmalonic aciduria type B or vitamin B12-responsive methylmalonicaciduria of cblB complementation type; MIM:251110). Affected individuals have methylmalonic aciduria and metabolic ketoacidosis, despite a functional methylmalonyl-CoA mutase. In severe cases, newborns are lethargic, prone to vomiting and fail to thrive (Dobson et al. 2002).
			REACT_163944 (Reactome)	Transcobalamin 1 (TCN1 aka haptocorrin, HC) is a glycoprotein produced by many cells including gastric cells in response to go food intake (Johnston et al. 1989). It can also bind a large fraction of cobalamin (Cbl) in the general circulation. No functional significance for this general binding is presently known (Quadros 2010, Alpers & Russel-Jones 1999 (in Chemistry and Biochemistry of B12, Banerjee 1999)).
			REACT_163950 (Reactome)	Biotin (Btn) acts as a coenzyme to 4 carboxylases which exist in their inactive apo forms. In the cytosol, these apo carboxylases are biotinylated to their active halo forms by the activity of biotin-protein ligase (HCLS) (Ingaramo & Beckett 2012, Hiratsuka et al. 1998, Bailey et al. 2010). Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka biotin-responsive multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of multiple carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). Pyruvate carboxylase (PC) is homotetrameric, binds 1 Mn2+ and 1 Btn per PC subunit (Xiang & Tong 2008). The exact order in which this complex is constructed is unknown.
			REACT_163988 (Reactome)	Methionine synthase reductase (MTRR) is involved in reducing B12r (cob(II)alamin) to B12s (cob(I)alamin), the cofactor form used by methionine synthase (MTR) to become functional. Regeneration of functional MTR requires reductive methylation via a reaction catalyzed by MTRR in which S-adenosylmethionine (SAM) is used as a methyl donor. MTRR requires 1 FMN and 1 FAD per subunit for activity (Wolthers et al. 2007). MTRR exists a stable complex with MTR, bound through their FMN-binding and C-terminal activation domains respectively (Wolthers & Scrutton 2007, Wolthers & Scrutton 2009). Defects in MTRR cause methylcobalamin deficiency type E (cblE; MIM:236270) (Wilson et al. 1999). Patients with cblE exhibit megaloblastic anemia and hyperhomocysteinemia. SAM is used as a methyl donor in many biological reactions and demethylation of methionine produces homocysteine. Remethylation is carried out by MTR but in cblE patients, MTR cannot be reduced by defective MTRR to form a functional enzyme thus homocysteine accumulates. Mutations in MTRR that cause cblE include Leu576del (Leclerc et al. 1998), S454L (Zavadakova et al. 2005) and the compound heterozygote G487R/M569Ifs*9 (Zavadakova et al. 2002). Wilson et al. showed that a 66A-G polymorphism, resulting in an Ile22Met (I22M) substitution, is associated with susceptibility to folate-sensitive neural tube defects (FS-NTD; MIM:601634) (Wilson et al. 1999b, Doolin et al. 2002). Serum deficiency of vitamin B12 increased the effect.
			REACT_163997 (Reactome)	Methylmalonyl-CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor and transfers an adenosyl group from AdoCbl to methymalonyl-CoA to form succinyl-CoA, a precursor for the citric acid cycle. MUT has a homodimeric structure and is located in the mitochondrial matrix. Defects in MUT cause methylmalonic aciduria type mut (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006). Methylmalonic aciduria type A protein (MMAA) (Dobson et al. 2002) is thought to act as a chaperone to MUT and is suggested to play a dual role with regards to MUT protection and reactivation. Defects in MMAA cause methylmalonic aciduria type cblA (MMAA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood (Dobson et al. 2002, Lerner-Ellis et al. 2004).
			REACT_164003 (Reactome)	Methylmalonic aciduria and homocystinuria type C protein (MMACHC aka cblC protein) is suggested to be involved in the binding and intracellular transport of cobalamin (Cbl aka vitamin B12). MMACHC can catalyse the removal of the "R" group from Cbl (eg dealkylation of ADOCbl and MeCbl or decyanation of CNCbl). It may also be involved in reducing Cbl (+3 oxidation state) to cob(II)alamin (B12r, vitamin B12r; +2 oxidation state) (Hannibal et al. 2009). B12r is either escorted by MMACHC to its destination enzyme partners in the mitochondria and cytosol or is exported through the basolateral membrane by the ATP-dependent ABCC1. Defects in MMACHC cause methylmalonic aciduria and homocystinuria type cblC (MMAHCC; MIM:277400). MMAHCC is the most common disorder of cobalamin metabolism and is characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MetCbl). Affected individuals may have developmental, haematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings (Lerner-Ellis et al. 2006).
			REACT_19 (Reactome)	Methylmalonyl-CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor and transfers an adenosyl group from AdoCbl to methylmalonyl-CoA to form succinyl-CoA, a precursor for the citric acid cycle. MUT has a homodimeric structure and is located in the mitochondrial matrix. Defects in MUT cause methylmalonic aciduria, mut type (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006). Methylmalonic aciduria type A protein (MMAA) is thought to act as a chaperone to MUT, the enzyme which utilises adenosylcobalamin (AdoCbl) as a cofactor. MMAA is suggested to play a dual role with regards to MUT protection and reactivation. Some AdoCbl-dependent enzymes undergo suicide inactivation after catalysis due to the oxidative inactivation of Cbl. MMAA is thought to play a protective role to prevent MUT being inactivated in this way. After the catalytic cycle when MUT is inactive, MMAA increases the enzymatic activity of MUT through exchange of the damaged cofactor. Whether this happens via GTP-mediated hydrolysis is unknown at present (Takahashi-Iniguez et al. 2011, Froese et al. 2010). Bacterial AdoCbl-containing enzymes possess reactivating factors which release the inactivated cofactor to allow the resulting apoenzyme to reconstitute into an active form. A bacterial orthologue of MMAA, MeaB, forms a stable complex with MUT and plays a role in its protection and reactivation (Padovani & Banerjee 2006). Defects in MMAA cause methylmalonic aciduria type cblA (cblA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood (Dobson et al. 2002, Lerner-Ellis et al. 2004).
			REACT_24937 (Reactome)	In order to get a sulfur atom for subsequent sulfuration reactions, cysteine is first desulfurated by NFS1 which transfers it onto a cysteine of MOCS3, yielding a protein persulfide (Marelja et al, 2008).
			REACT_25006 (Reactome)	Sulfur transfer onto MOCS2A is closely preceded by its adenylylation and deadenylylation. After release of MOCS2A-CO-S(1-), two cysteines on MOCS3 form a disulfide bridge. This means that MOCS3 has to be reduced to be able to participate in the next round. The reducing agent is not known (Marelja et al, 2008).
			REACT_25050 (Reactome)	Gephyrin, which stabilizes receptors on neuronal membranes, also catalyzes the transfer of a molybdenum ion onto the cofactor. The mechanism was elucidated in plants but, as the pathway is highly conserved, human gephyrin can complement missing plant proteins. Doubts remain about the actual molybdenum donor, probably molybdate, and whether a copper ion is possibly bound and removed (Stallmeyer et al, 1999).
			REACT_25068 (Reactome)	GTP cyclizes in a reaction involving radicals of S-adenosylmethionine, catalyzed by the iron-sulfur cluster dimeric MOCS1. The intermediate result is called precursor Z (Hanzelmann et al, 2002; Hanzelmann et al, 2004).
			REACT_25070 (Reactome)	Thiamin triphosphate (ThTP) is believed to be synthesized from thiamin diphosphate (ThDP), catalyzed by ThDP kinase (TDPK), an enzyme that remains poorly characterized (Nishino et al, 1983).
			REACT_25109 (Reactome)	Pyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxine (PDX) to form pyridoxine phosphate (PDXP) (Lee et al. 2000, di Salvo et al. 2004).
			REACT_25122 (Reactome)	While the biosynthesis of the molybdenum cofactor for sulfite oxidase is finished after molybdenum ion insertion, human xanthine oxidase and aldehyde oxidase will only show activity with this cofactor when one of the oxygens bound to molybdenum is replaced with sulfur. The exchange is catalyzed by the MOCOS cysteine desulfurase (Ichida et al, 2001).
			REACT_25127 (Reactome)	Pyridoxine-5'-phosphate oxidase (PNPO) is able to oxidize pyridoxamine phosphate (PXAP) to pyridoxal 5'-phosphate (PXLP) (Kang et al. 2004).
			REACT_25137 (Reactome)	Thiamin triphosphate (ThTP) can transfer phosphate to a few proteins. Animal tissues contain a membrane-associated as well as a soluble thiamine triphosphatase that can dephosphorylate ThTP. Only the soluble enzyme was characterized in calf (Lakaye et al, 2002).
			REACT_25295 (Reactome)	Pyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxal (PXL) to form pyridoxal 5'-phosphate (PXLP) (Lee et al. 2000, di Salvo et al. 2004).
			REACT_25323 (Reactome)	Pyridoxal kinase (PDXK) catalyzes the ATP-dependent phosphorylation of pyridoxamine (PXA) to form pyridoxamine phosphate (PXAP) (Lee et al. 2000, di Salvo et al. 2004).
			REACT_25348 (Reactome)	Pyridoxine-5'-phosphate oxidase (PNPO) is able to oxidize pyridoxine phosphate (PDXP) to pyridoxal 5'-phosphate (PXLP) (Kang et al. 2004).
			REACT_25353 (Reactome)	After the MOCS2A dimer is loaded with two sulfur atoms, their sequential deposition on the precursor Z molecule, with ring cleavage, is catalyzed by the MOCS2B half of the MOCS2 tetramer (Leimkuhler et al, 2003; Wuebbens & Rajagopalan, 2002).
			REACT_6739 (Reactome)	A methyl group from methylcobalamin (MeCbl) is transferred to homocysteine (HCYS), forming methionine (L-Met) (Leclerc et al. 1996). MTR is now in an inactive state as its cofactor state, B12r (cob(II)alamin), requires reduction to B12s (cob(I)alamin) to reactivate the enzyme. This is performed by methionine synthase reducatse (MTRR).
RFK:Mg2+		mim-catalysis	REACT_11232 (Reactome)
	RIB	Arrow	REACT_11171 (Reactome)
	RIB	Arrow	REACT_163635 (Reactome)
RIB			REACT_11232 (Reactome)
RIB			REACT_163635 (Reactome)
SLC19A1		mim-catalysis	REACT_11162 (Reactome)
SLC19A2/3		mim-catalysis	REACT_11081 (Reactome)
SLC25A16		mim-catalysis	REACT_11209 (Reactome)
SLC25A32		mim-catalysis	REACT_11143 (Reactome)
SLC25A32		mim-catalysis	REACT_11219 (Reactome)
SLC46A1		mim-catalysis	REACT_11104 (Reactome)
SLC46A1		mim-catalysis	REACT_11190 (Reactome)
SLC52A3		mim-catalysis	REACT_163635 (Reactome)
SLC5A6		mim-catalysis	REACT_11072 (Reactome)
SLC5A6		mim-catalysis	REACT_11142 (Reactome)
	SOG-MOCS2	Arrow	REACT_25006 (Reactome)
	SUCC-CoA	Arrow	REACT_19 (Reactome)
SVCT1/2		mim-catalysis	REACT_11120 (Reactome)
	TCN1:Cbl	Arrow	REACT_163895 (Reactome)
	TCN1:Cbl	Arrow	REACT_163944 (Reactome)
TCN1:Cbl			REACT_163923 (Reactome)
TCN1			REACT_163895 (Reactome)
TCN1			REACT_163944 (Reactome)
	TCN2:Cbl:CD320	Arrow	REACT_163657 (Reactome)
TCN2:Cbl:CD320			REACT_163909 (Reactome)
	TCN2:Cbl	Arrow	REACT_163637 (Reactome)
	TCN2:Cbl	Arrow	REACT_163761 (Reactome)
	TCN2:Cbl	Arrow	REACT_163909 (Reactome)
TCN2:Cbl			REACT_163656 (Reactome)
TCN2:Cbl			REACT_163657 (Reactome)
TCN2:Cbl			REACT_163761 (Reactome)
	TCN2	Arrow	REACT_163656 (Reactome)
TCN2			REACT_163637 (Reactome)
TDPK		mim-catalysis	REACT_25070 (Reactome)
	THF	Arrow	REACT_11143 (Reactome)
	THF	Arrow	REACT_11170 (Reactome)
	THF	Arrow	REACT_11219 (Reactome)
	THF	Arrow	REACT_163641 (Reactome)
	THFPG	Arrow	REACT_11083 (Reactome)
	THFPG	Arrow	REACT_11108 (Reactome)
	THFPG	Arrow	REACT_11134 (Reactome)
THFPG			REACT_11109 (Reactome)
THFPG			REACT_11159 (Reactome)
THF			REACT_11083 (Reactome)
THF			REACT_11134 (Reactome)
THF			REACT_11143 (Reactome)
THF			REACT_11219 (Reactome)
	THMN	Arrow	REACT_11081 (Reactome)
THMN			REACT_11081 (Reactome)
THMN			REACT_11233 (Reactome)
THTPA:Mg2+		mim-catalysis	REACT_25137 (Reactome)
	ThDP	Arrow	REACT_11233 (Reactome)
	ThDP	Arrow	REACT_25137 (Reactome)
ThDP			REACT_25070 (Reactome)
	ThTP	Arrow	REACT_25070 (Reactome)
ThTP			REACT_25137 (Reactome)
	VitC	Arrow	REACT_11095 (Reactome)
	VitC	Arrow	REACT_11100 (Reactome)
	VitC	Arrow	REACT_11120 (Reactome)
VitC			REACT_11120 (Reactome)
	dADE	Arrow	REACT_25068 (Reactome)
	hCBXs	Arrow	REACT_163704 (Reactome)
hCBXs			REACT_163704 (Reactome)
hCBXs			REACT_163820 (Reactome)
holo-MOCS1		mim-catalysis	REACT_25068 (Reactome)
	sulfurated MoCo	Arrow	REACT_25122 (Reactome)
unknown peptidase		mim-catalysis	REACT_163820 (Reactome)
unknown peptidase		mim-catalysis	REACT_163922 (Reactome)