2-アミノ-4-メルカプトブタン酸

Nitrosylation converts homocysteine (Hcy) into a methionine analogue, S-nitroso-Homocysteine, which can substitute for methionine in protein synthesis in biological systems. In humans, homocyteine-thiolactone modifies proteins posttranslationally by forming adducts in which homocysteine is linked by amide bonds to epsilon-amino group of protein lysine residues (Hcy-epsilonN-Lys-protein). Levels of homocystine bound by amide or peptide linkages (Homocysteine-N-protein) in human plasma proteins are directly related to plasma 'total homocysteine' levels. Homocysteine-N-hemoglobin and Homocysteine-N-albumin constitute a major pool of homocysteine in human blood, larger than 'total homocysteine' pool. Homocysteine-thiolactone is present in human plasma. Modification with Homocysteine-thiolactone leads to protein damage and induces immune response. Autoantibodies that specifically recognize the Homocysteine-epsilonN-Lys-epitope on Homocysteine-thiolactone-modified proteins occur in humans. The ability of Homocysteine to interfere with protein biosynthesis, which causes protein damage, induces cell death and elicits immune response, is likely a key contributor to the toxicity of homocysteine (A15343). Uremic toxins such as homocysteine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

Moderately high levels of homocysteine produce no overt symptoms. Extremely high levels in adults over extended periods of times can lead to the usual symptoms of heart disease (high blood pressure, atherosclerosis, shortness of breath, poor exercise tolerance, etc.). Individuals with genetic forms of homocysteinuria experience such symptoms as dislocation of the lenses in the eyes, nearsightedness, abnormal blood clots, osteoporosis (weakening of the bones), learning disabilities and developmental problems. As a uremic toxin, high levels of homocysteine in adults can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.