Transport of glycerol from adipocytes to liver by aquaporins (Homo sapiens)

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1, 21, 2, 19, 201, 2, 91, 2, 8-101, 21-71, 2, 8-101, 2, 11-18endoplasmic reticulum lumenstored secretory granulenucleoplasmcytosolextracellular regionAcyl GhrelinFatty AcidsSignal Peptidase ComplexProghrelin and Pro-des-Gln14-ghrelinGlucagonGrowth HormoneKrueppel-like factor 4Decanoic acidPreproghrelin and prepro-des-Gln14-ghrelinPlatelet-activating factor acetylhydrolaseLeptinAcyl GhrelinButyrylcholinesteraseProghrelinGhrelin O-acyltransferaseDes-acyl GhrelinOctanoic acidPC1/3alpha-D-glucoseAcyl ProghrelinDecanoyl ProghrelininsulinC-GhrelinInsulin-like growth factorC-GhrelinOctanoyl Proghrelin


Description

Ghrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the major source of ghrelin), hypothalamus, pituitary, adrenal gland, thyroid, breast, ovary, placenta, fallopian tube, testis, prostate, liver, gall bladder, pancreas, fat tissue, human lymphocytes, spleen, kidney, lung, skeletal muscle, myocardium, vein and skin. Ghrelin binds the GHS-R1a receptor present in hypothalamus pituitary, and other tissues. Binding causes appetite stimulation and release of growth hormone. Levels of circulating ghrelin rise during fasting, peak before a meal, and fall according to the calories ingested.
Preproghrelin is cleaved to yield proghrelin which is then acylated by ghrelin O-acyltransferase to yield octanoyl ghrelin and decanoyl ghrelin. Only octanoyl ghrelin is able to bind and activate the GHS-R1a receptor. Unacylated ghrelin (des-acyl ghrelin) is also present in plasma but its function is controversial.
Acyl proghrelin is cleaved by prohormone convertase 1/3 to yield the mature acyl ghrelin and C-ghrelin. Secretion of ghrelin is inhibited by insulin, growth hormone (somatotropin), leptin, glucose, glucagon, and fatty acids. Secretion is stimulated by insulin-like growth factor-1 and muscarinic agonists.
In the bloodstream acyl ghrelin is deacylated by butyrylcholinesterase and platelet-activating factor acetylhydrolase. Other enzymes may also deacylate acyl ghrelin.

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Bibliography

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  1. Marrades MP, Milagro FI, Martínez JA, Moreno-Aliaga MJ.; ''Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers.''; PubMed Europe PMC Scholia
  2. Padma S, Smeltz AM, Banks PM, Iannitti DA, McKillop IH.; ''Altered aquaporin 9 expression and localization in human hepatocellular carcinoma.''; PubMed Europe PMC Scholia
  3. Tsukaguchi H, Weremowicz S, Morton CC, Hediger MA.; ''Functional and molecular characterization of the human neutral solute channel aquaporin-9.''; PubMed Europe PMC Scholia
  4. Maeda N, Hibuse T, Funahashi T.; ''Role of aquaporin-7 and aquaporin-9 in glycerol metabolism; involvement in obesity.''; PubMed Europe PMC Scholia
  5. Frühbeck G, Catalán V, Gómez-Ambrosi J, Rodríguez A.; ''Aquaporin-7 and glycerol permeability as novel obesity drug-target pathways.''; PubMed Europe PMC Scholia
  6. Kondo H, Shimomura I, Kishida K, Kuriyama H, Makino Y, Nishizawa H, Matsuda M, Maeda N, Nagaretani H, Kihara S, Kurachi Y, Nakamura T, Funahashi T, Matsuzawa Y.; ''Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation.''; PubMed Europe PMC Scholia
  7. Ohgusu Y, Ohta KY, Ishii M, Katano T, Urano K, Watanabe J, Inoue K, Yuasa H.; ''Functional characterization of human aquaporin 9 as a facilitative glycerol carrier.''; PubMed Europe PMC Scholia
  8. Elkjaer M, Vajda Z, Nejsum LN, Kwon T, Jensen UB, Amiry-Moghaddam M, Frøkiaer J, Nielsen S.; ''Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain.''; PubMed Europe PMC Scholia
  9. Viadiu H, Gonen T, Walz T.; ''Projection map of aquaporin-9 at 7 A resolution.''; PubMed Europe PMC Scholia
  10. Kuriyama H, Kawamoto S, Ishida N, Ohno I, Mita S, Matsuzawa Y, Matsubara K, Okubo K.; ''Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability.''; PubMed Europe PMC Scholia
  11. Fain JN, Buehrer B, Bahouth SW, Tichansky DS, Madan AK.; ''Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue.''; PubMed Europe PMC Scholia
  12. Rojek A, Praetorius J, Frøkiaer J, Nielsen S, Fenton RA.; ''A current view of the mammalian aquaglyceroporins.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
116663view12:14, 9 May 2021EweitzOntology Term : 'hepatocyte' added !
116662view12:14, 9 May 2021EweitzOntology Term : 'fat cell' added !
116660view11:47, 9 May 2021EweitzModified title
115067view17:01, 25 January 2021ReactomeTeamReactome version 75
113511view11:58, 2 November 2020ReactomeTeamReactome version 74
112711view16:11, 9 October 2020ReactomeTeamReactome version 73
101626view11:49, 1 November 2018ReactomeTeamreactome version 66
101162view21:35, 31 October 2018ReactomeTeamreactome version 65
100688view20:08, 31 October 2018ReactomeTeamreactome version 64
100238view16:53, 31 October 2018ReactomeTeamreactome version 63
99790view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99341view12:48, 31 October 2018ReactomeTeamreactome version 62
94036view13:52, 16 August 2017ReactomeTeamreactome version 61
93659view11:30, 9 August 2017ReactomeTeamreactome version 61
88358view16:30, 1 August 2016FehrhartOntology Term : 'transport pathway' added !
88357view16:29, 1 August 2016FehrhartOntology Term : 'gluconeogenesis pathway' added !
86778view09:26, 11 July 2016ReactomeTeamreactome version 56
83221view10:25, 18 November 2015ReactomeTeamVersion54
81754view09:55, 26 August 2015ReactomeTeamVersion53
76897view08:17, 17 July 2014ReactomeTeamFixed remaining interactions
76602view11:58, 16 July 2014ReactomeTeamFixed remaining interactions
75933view09:58, 11 June 2014ReactomeTeamRe-fixing comment source
75635view10:51, 10 June 2014ReactomeTeamReactome 48 Update
74990view13:50, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74634view08:41, 30 April 2014ReactomeTeamReactome46
45102view22:10, 6 October 2011KhanspersOntology Term : 'ghrelin secreting cell' added !
42141view22:00, 4 March 2011MaintBotAutomatic update
39952view05:58, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
Acyl Ghrelin ProteinREACT_20017 (Reactome)
Acyl Ghrelin ProteinREACT_20031 (Reactome)
Acyl Proghrelin ProteinREACT_20024 (Reactome)
Butyrylcholinesterase ProteinP06276 (UniProt)
C-Ghrelin ProteinQ9UBU3-1 (UniProt)
Decanoic acid Metabolite30813 (ChEBI)
Decanoyl Proghrelin ProteinQ9UBU3-1 (UniProt)
Des-acyl Ghrelin ProteinREACT_19664 (Reactome)
Fatty Acids Metabolite35366 (ChEBI)
Ghrelin O-

acyltransferase

ProteinQ96T53 (UniProt)
Glucagon ProteinP01275 (UniProt)
Growth

Hormone

ProteinP01241 (UniProt) Growth hormone is typically used to refer to the endogenous hormone - somatotropin is reserved for synthetic hormone produced by recombinant technology.
Insulin-like growth

factor

ComplexREACT_3524 (Reactome)
Krueppel-like factor 4 ProteinO43474 (UniProt)
Leptin ProteinP41159 (UniProt)
Octanoic acid Metabolite28837 (ChEBI)
Octanoyl Proghrelin ProteinQ9UBU3-1 (UniProt)
PC1/3 ProteinP29120 (UniProt)
Platelet-activating

factor acetylhydrolase

ProteinQ13093 (UniProt)
Preproghrelin and

prepro-des-Gln14- ghrelin

ProteinREACT_19780 (Reactome)
Proghrelin ProteinQ9UBU3-1 (UniProt)
Proghrelin and Pro-

des-Gln14-ghrelin

ProteinREACT_19492 (Reactome)
Signal Peptidase

Complex

ComplexREACT_15945 (Reactome)
alpha-D-glucose Metabolite17925 (ChEBI)
insulin ComplexREACT_5828 (Reactome)

Annotated Interactions

No annotated interactions

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