| Record Information |
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| Version | 1.0 |
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| Created at | 2005-11-16 15:48:42 UTC |
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| Updated at | 2020-11-24 22:13:54 UTC |
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| NP-MRD ID | NP0000234 |
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| Secondary Accession Numbers | None |
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| Natural Product Identification |
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| Common Name | S-Adenosylhomocysteine |
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| Description | S-Adenosyl-L-homocysteine (SAH) is formed by the demethylation of S-adenosyl-L-methionine. S-Adenosylhomocysteine (AdoHcy or SAH) is also the immediate precursor of all of the homocysteine produced in the body. The reaction is catalyzed by S-adenosylhomocysteine hydrolase and is reversible with the equilibrium favoring formation of SAH. In vivo, the reaction is driven in the direction of homocysteine formation by the action of the enzyme adenosine deaminase which converts the second product of the S-adenosylhomocysteine hydrolase reaction, adenosine, to inosine. Except for methyl transfer from betaine and from methylcobalamin in the methionine synthase reaction, SAH is the product of all methylation reactions that involve S-adenosylmethionine (SAM) as the methyl donor. Methylation is significant in epigenetic regulation of protein expression via DNA and histone methylation. The inhibition of these SAM-mediated processes by SAH is a proven mechanism for metabolic alteration. Because the conversion of SAH to homocysteine is reversible, with the equilibrium favoring the formation of SAH, increases in plasma homocysteine are accompanied by an elevation of SAH in most cases. Disturbances in the transmethylation pathway indicated by abnormal SAH, SAM, or their ratio have been reported in many neurodegenerative diseases, such as dementia, depression, and Parkinson's disease (PMID: 18065573 , 17892439 ). Therefore, when present in sufficiently high levels, S-adenosylhomocysteine can act as an immunotoxin and a metabotoxin. An immunotoxin disrupts, limits the function, or destroys immune cells. A metabotoxin is an endogenous metabolite that causes adverse health effects at chronically high levels. Chronically high levels of S-adenosylhomocysteine are associated with S-adenosylhomocysteine (SAH) hydrolase deficiency and adenosine deaminase deficiency. S-Adenosylhomocysteine forms when there are elevated levels of homocysteine and adenosine. S-Adenosyl-L-homocysteine is a potent inhibitor of S-adenosyl-L-methionine-dependent methylation reactions. It is toxic to immature lymphocytes and can lead to immunosuppression (PMID: 221926 ). |
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| Structure | N[C@@H](CCSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N)C(O)=O InChI=1S/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)/t6-,7+,9+,10+,13+/m0/s1 |
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| Synonyms | | Value | Source |
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| (2S)-2-Amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)butanoic acid | ChEBI | | 2-S-Adenosyl-L-homocysteine | ChEBI | | Adenosyl-L-homocysteine | ChEBI | | Adenosylhomocysteine | ChEBI | | AdoHcy | ChEBI | | S-(5'-Adenosyl)-L-homocysteine | ChEBI | | S-[1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl]-L-homocysteine | ChEBI | | SAH | ChEBI | | (2S)-2-Amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)butanoate | Generator | | (2S)-2-Amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulphanyl)butanoate | Generator | | (2S)-2-Amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulphanyl)butanoic acid | Generator | | S-[1-(Adenin-9-yl)-1,5-dideoxy-b-D-ribofuranos-5-yl]-L-homocysteine | Generator | | S-[1-(Adenin-9-yl)-1,5-dideoxy-β-D-ribofuranos-5-yl]-L-homocysteine | Generator | | (S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine | HMDB | | 5'-Deoxy-S-adenosyl-L-homocysteine | HMDB | | 5'-S-(3-Amino-3-carboxypropyl)-5'-thio-L-adenosine | HMDB | | Adenosyl-homo-cys | HMDB | | Adenosylhomo-cys | HMDB | | Formycinylhomocysteine | HMDB | | L-5'-S-(3-Amino-3-carboxypropyl)-5'-thior-adenosine | HMDB | | L-S-Adenosyl-homocysteine | HMDB | | L-S-Adenosylhomocysteine | HMDB | | S-(5'-Deoxyadenosin-5'-yl)-L-homocysteine | HMDB | | S-(5'-Deoxyadenosine-5')-L-homocysteine | HMDB | | S-Adenosyl-homocysteine | HMDB | | S-Adenosyl-L-homocysteine | HMDB | | Adenosylhomocysteine, S | HMDB | | S Adenosylhomocysteine | HMDB |
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| Chemical Formula | C14H20N6O5S |
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| Average Mass | 384.4110 Da |
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| Monoisotopic Mass | 384.12159 Da |
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| IUPAC Name | (2S)-2-amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}sulfanyl)butanoic acid |
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| Traditional Name | S-adenosyl-L-homocysteine |
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| CAS Registry Number | 979-92-0 |
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| SMILES | N[C@@H](CCSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N)C(O)=O |
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| InChI Identifier | InChI=1S/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)/t6-,7+,9+,10+,13+/m0/s1 |
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| InChI Key | ZJUKTBDSGOFHSH-WFMPWKQPSA-N |
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| Experimental Spectra |
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| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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| 1D NMR | 1H NMR Spectrum (1D, 600 MHz, 100%_DMSO, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum | | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, 100%_DMSO, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum |
| | Predicted Spectra |
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| Not Available | | Chemical Shift Submissions |
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| Not Available | | Species |
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| Species of Origin | |
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| Species Where Detected | |
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| Chemical Taxonomy |
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| Description | Belongs to the class of organic compounds known as 5'-deoxy-5'-thionucleosides. These are 5'-deoxyribonucleosides in which the ribose is thio-substituted at the 5'position by a S-alkyl group. |
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| Kingdom | Organic compounds |
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| Super Class | Nucleosides, nucleotides, and analogues |
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| Class | 5'-deoxyribonucleosides |
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| Sub Class | 5'-deoxy-5'-thionucleosides |
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| Direct Parent | 5'-deoxy-5'-thionucleosides |
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| Alternative Parents | |
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| Substituents | - 5'-deoxy-5'-thionucleoside
- N-glycosyl compound
- Glycosyl compound
- 6-aminopurine
- Alpha-amino acid
- Alpha-amino acid or derivatives
- Pentose monosaccharide
- L-alpha-amino acid
- Imidazopyrimidine
- Purine
- Hydroxy fatty acid
- Aminopyrimidine
- Thia fatty acid
- Pyrimidine
- Fatty acyl
- Monosaccharide
- Imidolactam
- N-substituted imidazole
- Tetrahydrofuran
- Imidazole
- Azole
- Heteroaromatic compound
- Secondary alcohol
- Amino acid or derivatives
- Amino acid
- 1,2-diol
- Oxacycle
- Azacycle
- Carboxylic acid derivative
- Carboxylic acid
- Organoheterocyclic compound
- Dialkylthioether
- Sulfenyl compound
- Thioether
- Monocarboxylic acid or derivatives
- Organic oxide
- Organopnictogen compound
- Alcohol
- Carbonyl group
- Organic oxygen compound
- Amine
- Hydrocarbon derivative
- Organic nitrogen compound
- Primary amine
- Primary aliphatic amine
- Organosulfur compound
- Organooxygen compound
- Organonitrogen compound
- Aromatic heteropolycyclic compound
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| Molecular Framework | Aromatic heteropolycyclic compounds |
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| External Descriptors | |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | 209 - 211 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| General References | - Augoustides-Savvopoulou P, Luka Z, Karyda S, Stabler SP, Allen RH, Patsiaoura K, Wagner C, Mudd SH: Glycine N -methyltransferase deficiency: a new patient with a novel mutation. J Inherit Metab Dis. 2003;26(8):745-59. [PubMed:14739680 ]
- Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
- Hershfield MS, Kredich NM, Koller CA, Mitchell BS, Kurtzberg J, Kinney TR, Falletta JM: S-adenosylhomocysteine catabolism and basis for acquired resistance during treatment of T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin alone and in combination with 9-beta-D-arabinofuranosyladenine. Cancer Res. 1983 Jul;43(7):3451-8. [PubMed:6601986 ]
- Miller AL: The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev. 2003 Feb;8(1):7-19. [PubMed:12611557 ]
- Struys EA, Jansen EE, de Meer K, Jakobs C: Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Clin Chem. 2000 Oct;46(10):1650-6. [PubMed:11017945 ]
- Wang J, Dudman NP, Wilcken DE: Effects of homocysteine and related compounds on prostacyclin production by cultured human vascular endothelial cells. Thromb Haemost. 1993 Dec 20;70(6):1047-52. [PubMed:8165599 ]
- Palella TD, Schatz RA, Wilens TE, Fox IH: S-Adenosylhomocysteine accumulation and selective cytotoxicity in cultured T- and B-lymphocytes. J Lab Clin Med. 1982 Aug;100(2):269-78. [PubMed:6980250 ]
- van Guldener C, Stehouwer CD: Homocysteine and methionine metabolism in renal failure. Semin Vasc Med. 2005 May;5(2):201-8. [PubMed:16047272 ]
- Muskiet FA: The importance of (early) folate status to primary and secondary coronary artery disease prevention. Reprod Toxicol. 2005 Sep-Oct;20(3):403-10. [PubMed:15964170 ]
- Fowler B: Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. Semin Vasc Med. 2005 May;5(2):77-86. [PubMed:16047261 ]
- Gordon RK, Ginalski K, Rudnicki WR, Rychlewski L, Pankaskie MC, Bujnicki JM, Chiang PK: Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners. Eur J Biochem. 2003 Sep;270(17):3507-17. [PubMed:12919315 ]
- Metz J: Cobalamin deficiency and the pathogenesis of nervous system disease. Annu Rev Nutr. 1992;12:59-79. [PubMed:1354465 ]
- Mulder C, Schoonenboom NS, Jansen EE, Verhoeven NM, van Kamp GJ, Jakobs C, Scheltens P: The transmethylation cycle in the brain of Alzheimer patients. Neurosci Lett. 2005 Sep 30;386(2):69-71. [PubMed:16040194 ]
- Delabar U, Kloor D, Luippold G, Muhlbauer B: Simultaneous determination of adenosine, S-adenosylhomocysteine and S-adenosylmethionine in biological samples using solid-phase extraction and high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1999 Mar 19;724(2):231-8. [PubMed:10219663 ]
- Hermes M, von Hippel S, Osswald H, Kloor D: S-adenosylhomocysteine metabolism in different cell lines: effect of hypoxia and cell density. Cell Physiol Biochem. 2005;15(5):233-44. [PubMed:15956786 ]
- Weir DG, Molloy AM, Keating JN, Young PB, Kennedy S, Kennedy DG, Scott JM: Correlation of the ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine in the brain and cerebrospinal fluid of the pig: implications for the determination of this methylation ratio in human brain. Clin Sci (Lond). 1992 Jan;82(1):93-7. [PubMed:1310924 ]
- Wagner C, Koury MJ: S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine? Am J Clin Nutr. 2007 Dec;86(6):1581-5. [PubMed:18065573 ]
- Herrmann W, Obeid R: Biomarkers of folate and vitamin B(12) status in cerebrospinal fluid. Clin Chem Lab Med. 2007;45(12):1614-20. [PubMed:17892439 ]
- Kredich NM, Hershfield MS: S-adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin. Proc Natl Acad Sci U S A. 1979 May;76(5):2450-4. [PubMed:221926 ]
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