- (S )-2- amino-4- mercaptobutyric acid
- (S )-2- amino-4- mercaptobutansäure
- 6027-13-0 (L- enantiomer)
- 6027-14-1 (D - enantiomer)
- 454-29-5 (racemate )
233 ° C ( racemate)
Template: Infobox chemical / molecular formula search available
L- homocysteine ( Hcy ) is a naturally occurring (non- proteinogenic ) α -amino acid. It is an intermediate product in the metabolism of one- carbon transfer, and is formed by demethylation of S- L- methionine as a methyl donor. Increased blood levels of homocysteine may damage the blood vessels result. It is also closely associated with depression and dementia in old age. Normal laboratory values in the blood test are 5-10 micromol · l -1. For the regulation of homocysteine levels in the blood an adequate supply of betaine, and vitamins B12, B6 and folic acid is required. Treatment with the active substances on disease prevention is scientifically controversial.
Two molecules of homocysteine can connect via a disulfide bridge to homocystine. With increased levels of homocysteine in the blood homocystine is excreted in the urine ( homocystinuria ).
Homocysteine was discovered in 1932 by Vincent du Vigneaud in his work on sulfur-containing compounds. But only in 1962 recognized Carson and Neil the relationship between homocysteine and certain diseases. They found significantly increased Homocystinwerte in the urine of a group of children with intellectual disabilities and postulated an enzyme defect - the classical homocystinuria, caused by a defect of cystathionine β - transferase.
Homocysteine is present predominantly as the "inner salt " or zwitterion, whose formation can be explained by the fact that the proton of the carboxyl group migrates to the lone pair of the nitrogen atom of the amino group.
Zwitterions of L- homocysteine (left) and D- homocysteine (right)
In an electric field, the zwitterion migrates not because it is not loaded as a whole. Strictly speaking, this is at the isoelectric point ( at a certain pH value) of the case, wherein the homocysteine has its lowest solubility in water. Through its in comparison to cysteine additional CH2 group homocysteine can form a five-membered heterocyclic ring, a so-called thiolactone. Said cyclization reaction prevents the formation of stable peptide bonds. A protein containing homocysteine, therefore has the tendency to split.
From L- homocysteine and methyl - FH4 can be formed in a remethylation by the enzyme methionine synthase, the amino acid L- methionine. The methionine synthase requires vitamin B12 as a coenzyme. Alternatively, homocysteine is converted to methionine of the betaine - homocysteine - methyltransferase in the liver and kidney. Coenzyme for this reaction is betaine. Degrades homocysteine via the transsulfuration, a pure vitamin B6 -dependent step.
L -methionine is the one hand used for biochemical protein synthesis, on the other hand to the formation of S-adenosylmethionine ( SAM). SAM is the most important donor of methyl groups in the cellular metabolism. Has it delivered its methyl group, formed S- adenosyl homocysteine ( SAH), which is hydrolyzed to adenosine and L- homocysteine.
SAH inhibits methylation reactions, its reduction to homocysteine is therefore imperative to maintain methylation reactions. Is the breakdown of homocysteine disturbed, also the methylation reactions are disrupted in the cell.
Homocysteine and Genetics
Genetic polymorphism in homocysteine metabolism may affect enzyme function and thus the homocysteine metabolism under certain conditions. Often a change of the genetic information results in a slowing in the degradation of homocysteine and thus to an increase in the concentration of homocysteine in the blood. No clinically relevant polymorphisms are found ( methylenetetrahydrofolate reductase), especially in the enzyme MTHFR. The most common occurring mutation of the amino acid exchange Valine to Alanine at position 677, this form of the enzyme is thermolabile and leads to a up to 50% decreased performance at 37 ° C ( body temperature).
Homocysteine and external factors
Due to external factors, it may cause a mild to moderate increase in homocysteine concentration in blood. It should be remembered that an increase in homocysteine value in many cases is a multifactorial phenomenon triggered. Elevated homocysteine levels are found in alcohol consumption, smoking, frequent consumption of coffee, a sedentary lifestyle and obesity. Certain drugs can also influence the homocysteine concentration. Often a lack of folic acid and cobalamin (which can also be caused by inflammatory processes) leads to the increase in homocysteine levels. When strongly elevated homocysteine values occurrence is referred to as hyperhomocysteinemia.
Homocysteine as a risk factor
Homocysteine can cause direct toxic damage to the vessel wall and lead in different ways to an increased risk of thrombosis. Patients with known coronary heart disease are already loaded at slightly elevated homocysteine levels with an increased risk of cardiovascular events, while the data location in completely healthy people is uneven. With a homocysteine level above 15 micromol / L is uniform in several studies, an increased risk.
Although folic acid and B vitamins reduce homocysteine levels proven, the data situation for the vascular protective effect is not uniform. This can partly no effect on the risk of heart attack, but rather to reduce the risk of stroke ( up to 25% reduction) are shown. A systematic review by the Cochrane Collaboration found that the supplementation of B- vitamins for the prevention of heart disease does not matter. On the other hand showed a meta-analysis of the same year that the intake of folic acid in patients with known vascular damage and high vascular risk, particularly in patients with impaired renal function, prevent the progression of atherosclerosis can.
A study with patients suffering from multiple sclerosis, has revealed that the homocysteine levels correlated with the degree of depression. However, no correlation with their vitamin B12 and folic acid levels and the degree of disability, suggesting a previously unknown factor for the increased homocysteine levels showed.
Children who have had a stroke have significantly more often a disturbance in homocysteine metabolism than healthy people. In pregnant women, elevated homocysteine concentrations correlate with an increased risk of miscarriage and the development of pregnancy complications such as eclampsia. An increase in homocysteine levels in the mother's blood is also a risk factor for the development of neural tube defects in the child.
Patients with mild cognitive impairment and increased risk for Alzheimer's were treated in a study for 2 years with B vitamins or placebo. It was found that the average loss of brain mass in the relevant brain areas of Alzheimer's in the B -vitamin group was significantly lower and this result correlated with the reduction of elevated homocysteine levels.
Migraine patients with aura and increased levels of homocysteine benefited in a placebo -controlled study of vitamin B6, B12 and folic acid. After lowering homocysteine levels by 39 %, the Migäneanfälle reduced by 50%.
Increased levels of homocysteine is a risk factor in the development of all stages of Makuladegeneration.Die administration of a vitamin B complex (vitamin B6 - pyridoxine, Vitamin B9 - Folic acid and vitamin B12 - cyanocobalamin ) lowers homocysteine levels, this will significantly decrease (34%), the probability developing a macular degeneration.
In a clinical dose -finding study, different doses of vitamin B6, B12 and folic acid were tested on patients with elevated homocysteine levels. B6 = 50mg, vitamin B12 and folic acid = 1mg = 1mg was there with an average reduction of 55 % is most effective.
The determination of homocysteine in the blood is usually immunochemically or by HPLC. EDTA blood or fluoride is recommended as the material. Since homocysteine released by red blood cells, it does not require the addition of inhibitors (special tubes) to an increase of about 10% per hour. Recently, there is the possibility to measure the homocysteine level also close to the patient ( point-of- care testing ). This will make it possible to still tell the patient during the visit to the doctor the result of the investigation or initiate any necessary treatment without loss of time.
The cost of investigation of approximately 20 to 30 € will not be accepted in the normal case of health insurance and must be worn by the patient as a so -called individual health service itself.