Homocysteine is a non-protein α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (- CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. Homocysteine can be recycled into methionine or transformed into cysteine with the aid of specific B-vitamins.
A high level of homocysteine in the blood (hyperhomocysteinemia) makes an individual more vulnerable to endothelial cell injury, which results in inflammation in the blood vessels, which in turn may result in atherogenesis, which can result in ischemic injury. Hyperhomocysteinemia is therefore a possible risk aspect for coronary artery disease. Coronary artery disease takes place when an atherosclerotic plaque blocks blood flow to the coronary arteries, which supply the heart with oxygenated blood.
Hyperhomocysteinemia has actually been correlated with the occurrence of blood clots, cardiac arrest and strokes, though it is unclear whether hyperhomocysteinemia is an independent risk element for these conditions. Hyperhomoscyteinemia has actually likewise been associated with early pregnancy loss and with neural tube problems.
Biosynthesis and Biochemical Roles
Homocysteine is not obtained from the diet. Rather, it is biosynthesized from methionine through a multi-step procedure. First, methionine receives an adenosine group from ATP, a response catalyzed by S-adenosyl-methionine synthetase, to give S-adenosyl methionine (SAM).
SAM then moves the methyl group to an acceptor particle, (e.g., norepinephrine as an acceptor during epinephrine synthesis, DNA methyltransferase as an intermediate acceptor in the process of DNA methylation). The adenosine is then hydrolyzed to yield L-homocysteine. L-Homocysteine has two main developments: conversion via tetrahydrofolate (THF) back into L-methionine or conversion to L-cysteine.
Biosynthesis of Cysteine
Mammals biosynthesize the amino acid cysteine through homocysteine. Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This response uses pyridoxine (vitamin B6) as a cofactor. Cystathionine γ-lyase then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate. Bacteria and plants depend on a different path to produce cysteine, counting on O-acetylserine.
Methionine Salvage
Homocysteine can be recycled into methionine. This procedure uses N5-methyl tetrahydrofolate as the methyl donor and cobalamin (vitamin B12)- related enzymes.
Why are Homocysteine Levels Measured?
Elevated levels of homocysteine are connected with cardiovascular disease, stroke, and blood clots. If a person develops any of these illness and does not have increased risk factors such as smoking cigarettes, high blood pressure, high cholesterol, or diabetes, then the doctor frequently looks for more unusual causes and dangers, consisting of examining homocysteine levels in the blood.
Homocystinuria (implying elevated homocysteine in the urine) is an unusual, inherited disease in which impacted individuals have unusually high levels of homocysteine due to abnormal metabolism of the amino acid methionine. This condition is related to a number of various abnormality consisting of problems of the musculoskeletal system.
In infants who have a family history of homocystinuria, early screening for elevated levels might help avoid future illnesses connected to this metabolic problem. Moreover, infants and young children who have eye problems such as myopia (nearsightedness), changes in the lens of the eye, bone abnormalities, or unusual body shape might be evaluated for elevated homocysteine levels.
What are the Possible Symptoms and Signs of Elevated Homocysteine Levels?
Elevated homocysteine levels in the body do not cause any symptoms.
Elevated homocysteine levels impact the interior lining of capillary in the body, increasing the risk of atherosclerosis or narrowing of blood vessels. This can result in early cardiovascular disease and stroke.
There is a relationship in between the levels of homocysteine in the body and the size of the carotid arteries that provide the brain with blood; the higher homocysteine level, the narrower or more stenosed the carotid artery.
The risk of deep vein thrombosis and lung embolism may likewise be connected to elevated homocysteine levels in the body.
There might be a relationship in between elevated homocysteine levels and broken bones, particularly in the elderly.
Alzheimer’s disease and other types of dementia may be more frequently seen in patients with increased homocysteine in the blood.
In babies who have the hereditary condition homocystinuria, the inherited irregularities affect the body’s metabolic process of homocysteine to cysteine. This might result in dislocation of the lens in the eye, sunken chest, Marfan-type look (long thin physique), mental retardation, and seizures. Neonatal strokes might also be seen with high homocysteine levels.
In pregnancy, homocysteine levels have the tendency to reduce. Elevated homocysteine levels might be connected with some fetal abnormalities and with prospective blood vessel problems in the placenta, triggering abruption. There may also be an association with pre-eclampsia.
What are High Homocysteine Levels?
The majority of laboratories report regular homocysteine levels in the blood in between 4 and 15 micromoles/liter ( µmol/ L). Any measurement above 15 is thought about high. Ideal homocysteine levels are listed below 10 to 12.
Hyperhomocysteinemia has been categorized into moderate, intermediate, and severe types based upon the level of homocysteine as follows:
- Moderate (15 to 30 µmol/ L).
- Intermediate (30 to 100 µmol/ L).
- Severe (greater than 100 µmol/ L).
What Causes Elevated Homocysteine Levels?
Homocysteine levels increase in the body when the metabolism to cysteine of methionine to cysteine is impaired. This may be because of malnutritions in vitamin B6, vitamin B12, and folic acid.
While alcoholics have the tendency to be malnourished and lacking in B vitamins, alcohol (don’t consume alcohol, alcohol is harmful for health) might individually cause homocysteine levels in the blood to increase.
Can Elevated Homocysteine Levels Be Hereditary?
Hereditary irregularities might affect the body’s capability to metabolize homocysteine in to cytsteine, triggering elevation of homocysteine levels in the blood and urine. Screening is often recommended in babies if there is a family history of this disease.
How Can Homocysteine Levels Be Reduced?
The treatment for homocysteinuria is vitamin supplements with pyridoxine (vitamin B6), vitamin B12, and folic acid. The impacts of vitamin treatment may be monitored by routine, arranged blood tests. However, proof to support the value of treating elevated blood levels of homocysteine (except in cases of severely high levels) in the basic population is doing not have. For that reason, it is not recommended that people be treated with vitamins to lower homocysteine levels as a method to avoid vascular disease.
Some patients do not respond to the vitamin supplements and are considered pyridoxine-resistant. A diet low in methionine is advised in addition to the B vitamins.
Can Decreasing Homocysteine Levels Avoid the Risk of Heart Disease, Cardiovascular Disease, and Strokes?
There is controversy whether reducing homocysteine levels affects the risk of vascular disease like cardiovascular disease and stroke. At present there is inadequate proof to show that reducing these levels has any benefit in regards to disease avoidance, so treatment targeted at lowering blood homocysteine levels is not suggested for many people who do not have severe hyperhomocysteinemia.
Some research studies recommend that reducing homocysteine levels may reduce the risk of stroke. Nevertheless, while the general risk of stroke decreased in these studies, the seriousness of the stroke and the amount of disability were not impacted.
More significantly, medications that impact platelet function such as aspirin, clopidogrel (Plavix), and aspirin-dipyridamole (Aggrenox) are suggested and are effective as secondary stroke prevention medications. There is uncertainty whether the risk of heart disease is impacted.
Who Should Have Their Homocysteine Levels Tested?
Babies blood and urine are typically looked for elevated homocysteine levels if they have a family history of the disease, or if they have certain medical conditions consisting of eye lens dislocations, unusual (Marfan type) body shape, psychological retardation, or signs of stroke.
More youthful adults who have an early cardiac arrest, stroke, or blood clots are typically screened for blood clot irregularities including homocysteine blood tests.
Homocysteine levels are also typically measured when a patient suffers a heart attack or stroke and has no risk factors for that disease (smoking cigarettes, hypertension, high cholesterol, diabetes).
At present it is not recommended that people consuming regular diets with appropriate folate levels be screened for elevated homocysteine levels
