Homocysteine
In biochemistry, homocysteine is a "thiol-containing amino acid formed by a demethylation of methionine.[1]
Role in human disease
Homocystinuria
Homocystinuria is an "autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of cystathionine beta-synthase and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall, slender habitus, scoliosis, arachnodactyly, muscle weakness, genu varis, thin blond hair, malar flush, lens dislocations, an increased incidence of mental retardation, and a tendency to develop fibrosis of arteries, frequently complicated by cerebrovascular accidents and myocardial infarction.[2] Homozygous individuals have homocysteine levels that are five times the normal level.[3]
Hyperhomocysteinemia
Hyperhomocysteinemia is an "inborn error of methionine metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine beta-synthase and is a risk factor for coronary vascular disease."[4][5]
Methylenetetrahydrofolate reductase deficiency
About 10% of people are homozygous for the single gene mutation (cytosine is replaced by thymidine at base position 677) that reduces the activity of the enzyme methylenetetrahydrofolate reductase (MTHFR).[3][6] These individuals with TT genotype have a 20% increase in serum homocysteine levels and may have increased coronary heart disease.[3][6][7]
Treatment to reduce homocysteine levels
Randomized controlled trials have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality[8][9], reduced coronary heart disease[10][9] or improved cognition[11][12]
References
- ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 3.0 3.1 3.2 Wald DS, Wald NJ, Morris JK, Law M (November 2006). "Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence". BMJ 333 (7578): 1114–7. DOI:10.1136/bmj.39000.486701.68. PMID 17124224. PMC 1661741. Research Blogging.
- ↑ Anonymous (2024), Hyperhomocysteinemia (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Homocysteinemia. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
- ↑ 6.0 6.1 Wald DS, Law M, Morris JK (November 2002). "Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis". BMJ 325 (7374): 1202. PMID 12446535. PMC 135491. [e]
- ↑ 5,10-@methylenetetrahydrofolate reductase; MTHFR. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
- ↑ Jamison RL, Hartigan P, Kaufman JS, et al (September 2007). "Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial". JAMA 298 (10): 1163–70. DOI:10.1001/jama.298.10.1163. PMID 17848650. Research Blogging.
- ↑ 9.0 9.1 Ebbing M, Bleie Ø, Ueland PM, et al (August 2008). "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial". JAMA 300 (7): 795–804. DOI:10.1001/jama.300.7.795. PMID 18714059. Research Blogging.
- ↑ Bønaa KH, Njølstad I, Ueland PM, et al (April 2006). "Homocysteine lowering and cardiovascular events after acute myocardial infarction". N. Engl. J. Med. 354 (15): 1578–88. DOI:10.1056/NEJMoa055227. PMID 16531614. Research Blogging.
- ↑ McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM (June 2006). "A controlled trial of homocysteine lowering and cognitive performance". N. Engl. J. Med. 354 (26): 2764–72. DOI:10.1056/NEJMoa054025. PMID 16807413. Research Blogging.
- ↑ Aisen PS, Schneider LS, Sano M, et al (October 2008). "High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial". JAMA 300 (15): 1774–83. DOI:10.1001/jama.300.15.1774. PMID 18854539. Research Blogging.