- Homocysteine is the intermediate product of the transsulfuration pathway, theconversion of the amino acid methionine to cysteine (and thence to NAC, glutathione & taurine). Accomplished by enzyme cystathionine B-synthase (CBS). Requires cofactor pyroxidal 5-phosphate.
- Via remethylation, homocysteine is converted back to methionine via methionine synthase (MS). Requires methionine synthase reductase. (MSR)Catalyzed by methylene tetrahydrofolate reductase (MTHFR) and methylcobalamin (vitamin B12). Alternatively, a small amount of remethylation uses an alternate route with betaine as the methyl donor.
- On the NutriWest site, in a presentation of their product Homocysteine Redux, there's a good general description, with diagram, of the metabolic pathyways involving homocysteine. Unfortunately the discussion doesn't address the complications which mercury poisoning introduces.
- "Methionine is the only amino acid that creates homocysteine. People who eat foods that are high in methionine such as red meat and chicken may need more vitamin B6." A Lethal Misconception, LEF Magazine, March 1999
- Two names:
- Homocystinuria a more severe condition. Rare inborn errors of metabolism lead to urinary excretion of large amounts of homocystine combined with severely increased plasma tHcy concentrations, usually >100 µmol/L (25).
- defect in the trannsulfuration pathway / deficiency in CBS
- defect in the remethylation pathway / defective methylcobalamin synthesis or abnormality in MTHFR.
- Possible sources of abnormalities
- genetic predisposition
- genetic predisposition worsened by comorbid conditions and/or nutritional and environmental factors:
- abnormal MTHFR
- chronic renal failure
- methotrexate treatment
- oral contraceptive use
- consumption of animal proteins
- Research links high levels with
- Cardiovascular disease
- Alzheimer's Disease; here's the NIH report.
- Rheumatoid Arthritis
- "Adequate vitamins B6, B12 and folic acid need to be present to prevent the buildup of homocysteine [HCy] due to supplementation with methionine or SAMe. People who have serum homocysteine levels above 8 should not supplement with methionine or SAMe until homocysteine levels are between 4 and 8." (From "Alternatives to NSAIDs for Osteoarthritis," an interview with Dean Raffelock in the November, 2001 issue of the John R. Lee, MD Medical Letter. (pp 5-6)
- If it's elevated, possible methods of reducing homocysteine are
- Remethylation via
- Choline in the liver and kidney (but not the brain and heart)
- Folic acid and Vitamin B12 protect the brain and the heart.
- conversion into
- cysteine ...then eventually (if all goes well) into glutathione
- and alpha-ketobutyrate
- requires vitamin B6 (or P5P)
Low Homocysteine: Homocysteinemia causes strokes.
Tests for homocystinuria
- Urine screening for sulfur-containing amino acids: cyanide nitroprusside test. High rates of false-negative as well as false-positive results are reported.
- Neonatal screening: the Guthrie test, detects high levels of methionine in heel-stick blood. Performed routinely in several states for detection of phenylalanine, leucine, and methionine. Because of high false-negative results in homocystinuric patients, a recent report suggested lowering the threshold of methionine to qualify as abnormal.
- Quantitative tests for homocystine in urine and blood (commonly available). The blood specimen needs to be handled in a specific manner.
- Measurement of CBS activity in cultured fibroblasts provides definitive support for the diagnosis.
- Testing of amniotic cells and chorionic villi
- Genetic tests for CBS mutation
- Plastma homocysteine levels
- 5 March 02 - 7.8
- 14 September 04 -10
For More Infomation
- Metabolic Disease & Stroke: Homocystinuria/Homocysteinemia, by Pitchaiah Mandava, Thomas A Kent, Michael E DeBakey on the eMedicine site. Lots of useful information, unfortunately poorly written so that it's sometimes confusing. Bibliography.
- Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion, by Helga Refsum, A. David Smith1, Per M. Ueland, Ebba Nexo, Robert Clarke, Joseph McPartlin, Carole Johnston, Frode Engbaek, Jørn Schneede, Catherine McPartlin and John M. Scott. Clinical Chemistry. 2004;50:3-32.
- Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism, by A Wilson, D Leclerc, DS Rosenblatt and RA Gravel. Human Molecular Genetics, Vol 8, 2009-2016
- Hyperhomocysteinemia, on Wikipedia (a stub, but still good)
- Homocystinuria, on the MedLine Plus Medical Encyclopedia
- Disorder Factsheet for Professionals / Amino Acid Disorders / Homocystinuria, on the site of FELSI - Expanded Newborn Screening Using Tandem Mass Spectromety: financial, ethical, legal and social issues
- Another good discussion of all this is at Dr. Deborah Baker's Health and Detox Center.
- my pages
Last updated 18 September 2006