Choline catabolism (Homo sapiens)

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Bibliography

1. Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V.; ''Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.''; PubMed Europe PMC Scholia
2. Binzak BA, Wevers RA, Moolenaar SH, Lee YM, Hwu WL, Poggi-Bach J, Engelke UF, Hoard HM, Vockley JG, Vockley J.; ''Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency.''; PubMed Europe PMC Scholia
3. Eschenbrenner M, Jorns MS.; ''Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia.''; PubMed Europe PMC Scholia
4. Ueland PM.; ''Choline and betaine in health and disease.''; PubMed Europe PMC Scholia
5. Li F, Feng Q, Lee C, Wang S, Pelleymounter LL, Moon I, Eckloff BW, Wieben ED, Schaid DJ, Yee V, Weinshilboum RM.; ''Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization.''; PubMed Europe PMC Scholia
6. Hollenbeck CB.; ''An introduction to the nutrition and metabolism of choline.''; PubMed Europe PMC Scholia
7. Michel V, Bakovic M.; ''The solute carrier 44A1 is a mitochondrial protein and mediates choline transport.''; PubMed Europe PMC Scholia
8. Bar-joseph I, Pras E, Reznik-Wolf H, Marek-Yagel D, Abu-Horvitz A, Dushnitzky M, Goldstein N, Rienstein S, Dekel M, Pode-Shakked B, Zlotnik J, Benarrosh A, Gillery P, Hofliger N, Auray-Blais C, Garnotel R, Anikster Y.; ''Mutations in the sarcosine dehydrogenase gene in patients with sarcosinemia.''; PubMed Europe PMC Scholia
9. Wong JW, Chan CL, Tang WK, Cheng CH, Fong WP.; ''Is antiquitin a mitochondrial Enzyme?''; PubMed Europe PMC Scholia
10. Huang S, Lin Q.; ''Functional expression and processing of rat choline dehydrogenase precursor.''; PubMed Europe PMC Scholia
11. Porter RK, Scott JM, Brand MD.; ''Characterization of betaine efflux from rat liver mitochondria.''; PubMed Europe PMC Scholia
12. Binzak BA, Vockley JG, Jenkins RB, Vockley J.; ''Structure and analysis of the human dimethylglycine dehydrogenase gene.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ALDH7A1	Protein	P49419 (Uniprot-TrEMBL)
BETALD	Metabolite	CHEBI:15710 (ChEBI)
BET	Metabolite	CHEBI:17750 (ChEBI)
BHMT	Protein	Q93088 (Uniprot-TrEMBL)
BHMT:Zn2+ tetramer	Complex	R-HSA-6798211 (Reactome)
CH2O	Metabolite	CHEBI:16842 (ChEBI)
CHDH	Protein	Q8NE62 (Uniprot-TrEMBL)
Cho	Metabolite	CHEBI:15354 (ChEBI)
DMGDH	Protein	Q9UI17 (Uniprot-TrEMBL)
DMGDH:FAD	Complex	R-HSA-6797657 (Reactome)
DMGLY	Metabolite	CHEBI:17724 (ChEBI)
FAD	Metabolite	CHEBI:16238 (ChEBI)
FAD	Metabolite	CHEBI:16238 (ChEBI)
FADH2	Metabolite	CHEBI:17877 (ChEBI)
Gly	Metabolite	CHEBI:57305 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HCYS	Metabolite	CHEBI:17230 (ChEBI)
L-Met	Metabolite	CHEBI:57844 (ChEBI)
NAD+	Metabolite	CHEBI:15846 (ChEBI)
NADH	Metabolite	CHEBI:16908 (ChEBI)
SARC	Metabolite	CHEBI:15611 (ChEBI)
SARDH	Protein	Q9UL12 (Uniprot-TrEMBL)
SARDH:FAD	Complex	R-HSA-6797933 (Reactome)
SLC44A1	Protein	Q8WWI5 (Uniprot-TrEMBL)
Zn2+	Metabolite	CHEBI:29105 (ChEBI)

Annotated Interactions

Source	Target	Type	Database reference	Comment
ALDH7A1		mim-catalysis	R-HSA-6797955 (Reactome)
	BETALD	Arrow	R-HSA-6797961 (Reactome)
BETALD			R-HSA-6797955 (Reactome)
	BET	Arrow	R-HSA-6797955 (Reactome)
	BET	Arrow	R-HSA-6797957 (Reactome)
BET			R-HSA-1614654 (Reactome)
BET			R-HSA-6797957 (Reactome)
BHMT:Zn2+ tetramer		mim-catalysis	R-HSA-1614654 (Reactome)
	CH2O	Arrow	R-HSA-6797653 (Reactome)
	CH2O	Arrow	R-HSA-6797913 (Reactome)
CHDH		mim-catalysis	R-HSA-6797961 (Reactome)
	Cho	Arrow	R-HSA-6797956 (Reactome)
Cho			R-HSA-6797956 (Reactome)
Cho			R-HSA-6797961 (Reactome)
DMGDH:FAD		mim-catalysis	R-HSA-6797653 (Reactome)
	DMGLY	Arrow	R-HSA-1614654 (Reactome)
	DMGLY	Arrow	R-HSA-6797962 (Reactome)
DMGLY			R-HSA-6797653 (Reactome)
	FADH2	Arrow	R-HSA-6797961 (Reactome)
FAD			R-HSA-6797961 (Reactome)
	Gly	Arrow	R-HSA-6797913 (Reactome)
H2O			R-HSA-6797653 (Reactome)
H2O			R-HSA-6797913 (Reactome)
H2O			R-HSA-6797955 (Reactome)
HCYS			R-HSA-1614654 (Reactome)
	L-Met	Arrow	R-HSA-1614654 (Reactome)
NAD+			R-HSA-6797955 (Reactome)
	NADH	Arrow	R-HSA-6797955 (Reactome)
			R-HSA-1614654 (Reactome)	Remethylation of homocysteine (HCYS) to methionine (L-Met) can also proceed by using betaine (BET) as a methyl donor, which is oxidised to dimethylglycine (DMGLY). This reaction is also part of choline catabolism, thereby providing a link to folate-dependent, one-carbon metabolism (Li et al. 2008).
			R-HSA-6797653 (Reactome)	Mitochondrial dimethylglycine dehydrogenase (DMGDH) is an enzyme involved in the choline catabolic pathway, mediating the oxidative demethylation of dimethylglycine (DMGLY) to form sarcosine (SARC, aka methylglycine, MeGly) and formaldehyde (CH2O), an active 1-carbon unit (Binzak et al. 2000). DMGDH covalently binds one FAD cofactor per monomer. Defects in DMGDH cause DMGDH deficiency (DMGDHD; MIM:605850), a disorder characterised by a fishy odour and muscle fatigue with increased serum creatine kinase. Biochemically, increased levels of DMGLY are detected in the serum and urine (Binzak et al. 2001).
			R-HSA-6797913 (Reactome)	Mitochondrial sarcosine dehydrogenase (SARDH) oxidatively demethylates sarcosine (SARC, aka methylglycine) to glycine (Gly) and formaldehyde (CH2O), an active 1-carbon unit (Eschenbrenner & Jorns 1999, ). SARDH requires one FAD as cofactor, which is reduced during the reaction. Defects in SARDH cause sarcosinemia (SARCOS; MIM:268900), a disorder characterised by an increased concentration of sarcosine in plasma and increased sarcosine excretion in urine. The clinical phenotypes of sarcosinemia are diverse, ranging from normal (most common) to ones associated with mental retardation, growth delay and muscular abnormalities (Bar-joseph et al. 2012).
			R-HSA-6797955 (Reactome)	Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A1) is a multifunctional enzyme present in mitochondria, nucleus and the cytosol and plays an important role in protecting against hyperosmotic stress and metabolising toxic aldehydes. It is able to oxidise the osmolyte precursor betaine aldehyde (BETALD) to betaine (BET) (as well as the intermediate lysine degradation product, alpha-aminoadipic semialdehyde, not shown here) (Brocker et al. 2010). The mitochondrial isoform of ALDH7A1 is shown here.
			R-HSA-6797956 (Reactome)	The choline transporter-like protein 1 (SLC44A1) as an important mediator of choline transport across both the plasma membrane and the mitochondrial membrane. It is an essential step in the oxidation of Cho to betaine, which occurs in the mitochondrial matrix (Michel & Bakovic 2009).
			R-HSA-6797957 (Reactome)	Betaine (BET) is further metabolised in the cytosol and needs to translocate from the mitochondrial matrix to the cytosol. From rat studies, the process is suggested to be simple diffusion (Porter et al. 1993).
			R-HSA-6797961 (Reactome)	Mitochondrial choline dehydrogenase (CHDH), located on the inner mitochondrial membrane, catalyses the oxidation of choline (Cho) to betaine aldehyde (BETALD) using FAD as cofactor. Human CHDH activity is inferred from rat Chdh (Huang & Lin 2003).
			R-HSA-6797962 (Reactome)	Dimethylglycine (DMGLY) is either cleared by the kidneys or is further metabolised in the mitochondrion. Cytosolic DMGLY translocates to the mitochondrial matrix possibly by simple diffusion but the mechanism is unknown (Porter et al. 1993).
	SARC	Arrow	R-HSA-6797653 (Reactome)
SARC			R-HSA-6797913 (Reactome)
SARDH:FAD		mim-catalysis	R-HSA-6797913 (Reactome)
SLC44A1		mim-catalysis	R-HSA-6797956 (Reactome)