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Gene Review

ACSM3  -  acyl-CoA synthetase medium-chain family...

Homo sapiens

Synonyms: Acyl-CoA synthetase medium-chain family member 3, Acyl-coenzyme A synthetase ACSM3, mitochondrial, Butyrate--CoA ligase 3, Butyryl-coenzyme A synthetase 3, Middle-chain acyl-CoA synthetase 3, ...
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Disease relevance of ACSM3


Psychiatry related information on ACSM3

  • Our results demonstrated that chronic alcohol consumption in mice not only decreased hepatic S-adenosylmethionine levels but also increased hepatic SAH levels, which resulted in a significantly decreased S-adenosylmethionine-to-SAH ratio [6].
  • Reassurance and treatment of depressive symptoms could be important to improve the long-term outcome of PM SAH patients [7].
  • This study investigates the role of brain SAH in the cognitive and neurological disruption in Alzheimer's disease [8].
  • The most important changes from the previously reported method are a shorter derivatization reaction time, the use of a solid-phase extraction resulting in an increase of the method's sensitivity, and the use of only one chromatographic system to separate SAM and SAH (in which the use of an ion-pairing reagent in the mobile phase is avoided) [9].

High impact information on ACSM3


Chemical compound and disease context of ACSM3


Biological context of ACSM3


Anatomical context of ACSM3

  • In this study we have located the human homologue of the SA gene to chromosome 16p13.11, by a combination of fluorescence in-situ hybridization and analysis of somatic cell hybrids carrying different segments of chromosome 16 [18].
  • Transient expression of the SA protein in mammalian cells confirmed that it is expressed in mitochondria and has medium-chain fatty acid:CoA ligase activity [3].
  • Plasma SAH levels were positively correlated with intracellular lymphocyte SAH levels (r = 0.81; p < 0.001) and also with lymphocyte DNA hypomethylation (r = 0.74, p < 0.001) [14].
  • DESIGN: Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery [19].
  • The authors conclude that the elevated levels of TGF-beta1 in CSF after SAH are derived initially from blood and later from endogenous sources such as the choroid plexus [20].

Associations of ACSM3 with chemical compounds

  • CONCLUSIONS: SNPs in the MACS1 and SAH genes contribute to plasma levels of high-density lipoprotein cholesterol [12].
  • Haplotype analysis indicated that a haplotype defined by the I/D polymorphism of SAH and the L513S polymorphism in MACS2 was highly significantly associated with the triglyceride level [21].
  • The HIV-seropositive patients had significantly lower CSF concentrations of SAM (mean 77 [SD 25] vs 131 [35] nmol/l; p less than 0.001) and significantly higher concentrations of SAH (30.5 [6.8] vs 19.0 [7.1] nmol/l; p less than 0.001) than the controls [4].
  • S-adenosylhomocysteine (SAH) is product of methionine in transsulfuration pathway and a potent competitive inhibitor of most methyltransferases [6].
  • Mutation-associated decreases in SAH and SAMe could compromise needed cysteine availability to generate glutathione during oxidative stress [11].

Other interactions of ACSM3


Analytical, diagnostic and therapeutic context of ACSM3

  • The SA genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) with Pst I [22].
  • To extend this finding we carried out a case-control study of several recently identified polymorphisms in SAH: 1) an insertion/deletion of TTTAA at nucleotide --1037 in the promoter; 2) an insertion/deletion of two Alu like sequences in intron 1; and 3) an A-G variant in intron 12 located 7 bp upstream from exon 13 [2].
  • The previously observed associations between an SAH polymorphism and the waist-to-hip ratio appear to be due to linkage disequilibrium with the L513S polymorphism [21].
  • We therefore propose that Siva-1 or its SAH region can be used as a potentiator of cisplatin-based chemotherapy [23].
  • Using a sensitive new high pressure liquid chromatography method with coulometric electrochemical detection, plasma SAH levels in healthy young women were found to increase linearly with mild elevation in homocysteine levels (r = 0.73; p < 0.001); however, S-adenosylmethionine levels were not affected [14].


  1. Evaluation of the SA locus in human hypertension. Nabika, T., Bonnardeaux, A., James, M., Julier, C., Jeunemaitre, X., Corvol, P., Lathrop, M., Soubrier, F. Hypertension (1995) [Pubmed]
  2. Overweight, but not hypertension, is associated with SAH polymorphisms in Caucasians with essential hypertension. Benjafield, A.V., Iwai, N., Ishikawa, K., Wang, W.Y., Morris, B.J. Hypertens. Res. (2003) [Pubmed]
  3. Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension. Iwai, N., Katsuya, T., Mannami, T., Higaki, J., Ogihara, T., Kokame, K., Ogata, J., Baba, S. Circulation (2002) [Pubmed]
  4. Evidence of brain methyltransferase inhibition and early brain involvement in HIV-positive patients. Keating, J.N., Trimble, K.C., Mulcahy, F., Scott, J.M., Weir, D.G. Lancet (1991) [Pubmed]
  5. Hepatic transmethylation reactions in micropigs with alcoholic liver disease. Villanueva, J.A., Halsted, C.H. Hepatology (2004) [Pubmed]
  6. S-adenosylhomocysteine sensitizes to TNF-alpha hepatotoxicity in mice and liver cells: a possible etiological factor in alcoholic liver disease. Song, Z., Zhou, Z., Uriarte, S., Wang, L., Kang, Y.J., Chen, T., Barve, S., McClain, C.J. Hepatology (2004) [Pubmed]
  7. Cognitive and emotional consequences of perimesencephalic subarachnoid hemorrhage. Madureira, S., Canhão, P., Guerreiro, M., Ferro, J.M. J. Neurol. (2000) [Pubmed]
  8. Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cognitive function. Kennedy, B.P., Bottiglieri, T., Arning, E., Ziegler, M.G., Hansen, L.A., Masliah, E. Journal of neural transmission (Vienna, Austria : 1996) (2004) [Pubmed]
  9. Quantification of plasma S-adenosylmethionine and S-adenosylhomocysteine as their fluorescent 1,N(6)-etheno derivatives: an adaptation of previously described methodology. Castro, R., Struys, E.A., Jansen, E.E., Blom, H.J., de Almeida, I.T., Jakobs, C. Journal of pharmaceutical and biomedical analysis. (2002) [Pubmed]
  10. S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration. Shu, S., Mahadeo, D.C., Liu, X., Liu, W., Parent, C.A., Korn, E.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Keratin mutation primes mouse liver to oxidative injury. Zhou, Q., Ji, X., Chen, L., Greenberg, H.B., Lu, S.C., Omary, M.B. Hepatology (2005) [Pubmed]
  12. Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension. Haketa, A., Soma, M., Nakayama, T., Sato, M., Kosuge, K., Aoi, N., Matsumoto, K. J. Hypertens. (2004) [Pubmed]
  13. Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin. O'Hare, K.B., Hume, I.C., Scarlett, L., Chytrý, V., Kopecková, P., Kopecek, J., Duncan, R. Hepatology (1989) [Pubmed]
  14. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. Yi, P., Melnyk, S., Pogribna, M., Pogribny, I.P., Hine, R.J., James, S.J. J. Biol. Chem. (2000) [Pubmed]
  15. Quantification of serum and urinary S-adenosylmethionine and S-adenosylhomocysteine by stable-isotope-dilution liquid chromatography-mass spectrometry. Stabler, S.P., Allen, R.H. Clin. Chem. (2004) [Pubmed]
  16. Homocysteine potentiates the antiviral and cytostatic activity of those nucleoside analogues that are targeted at S-adenosylhomocysteine hydrolase. De Clercq, E., Cools, M., Balzarini, J. Biochem. Pharmacol. (1989) [Pubmed]
  17. Human SA gene locus as a candidate locus for essential hypertension. Iwai, N., Ohmichi, N., Hanai, K., Nakamura, Y., Kinoshita, M. Hypertension (1994) [Pubmed]
  18. Chromosomal assignment of the human SA gene to 16p13.11 and demonstration of its expression in the kidney. Samani, N.J., Whitmore, S.A., Kaiser, M.A., Harris, J., See, C.G., Callen, D.F., Lodwick, D. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  19. Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns. Guerra-Shinohara, E.M., Morita, O.E., Peres, S., Pagliusi, R.A., Sampaio Neto, L.F., D'Almeida, V., Irazusta, S.P., Allen, R.H., Stabler, S.P. Am. J. Clin. Nutr. (2004) [Pubmed]
  20. Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources. Flood, C., Akinwunmi, J., Lagord, C., Daniel, M., Berry, M., Jackowski, A., Logan, A. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  21. An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to multiple risk factors. Iwai, N., Mannami, T., Tomoike, H., Ono, K., Iwanaga, Y. Hypertension (2003) [Pubmed]
  22. Role of genetic polymorphism in the SA gene on the blood pressure and prognosis of renal function in patients with immunoglobulin A nephropathy. Narita, I., Saito, N., Goto, S., Shirasaki, A., Morioka, Y., Jin, S., Omori, K., Sakatsume, M., Arakawa, M., Gejyo, F. Hypertens. Res. (2002) [Pubmed]
  23. Expression of Siva-1 protein or its putative amphipathic helical region enhances cisplatin-induced apoptosis in breast cancer cells: effect of elevated levels of BCL-2. Chu, F., Barkinge, J., Hawkins, S., Gudi, R., Salgia, R., Kanteti, P.V. Cancer Res. (2005) [Pubmed]
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