Succinylacetoacetate (BioDeep_00000169723)

描述信息

Succinylacetoacetate is an intermediate that arises due to the incomplete breakdown of tyrosine (PMID: 7171740). It is produced as a result of defects in the enzyme called fumarylacetoacetase. Fumarylacetoacetase normally catalyzes the hydrolysis of 4-fumarylacetoacetate into fumarate and acetoacetate. If present in sufficiently high levels, succinylacetoacetate can act as an acidogen, an oncometabolite, and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. An oncometabolite is an endogenous metabolite that causes cancer. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of succinylacetoacetate are associated with tyrosinemia type I. Type I tyrosinemia is an inherited metabolic disorder due to a shortage of the enzyme fumarylacetoacetate hydrolase that is needed to break down tyrosine. Patients usually develop features such as hepatic necrosis, renal tubular injury, and hypertrophic cardiomyopathy. Neurologic and dermatologic manifestations are also possible as well as hepatocellular carcinoma. The urine of tyrosinemia patients has an odour of cabbage or rancid butter. Succinylacetoacetate is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of untreated tyrosinemia. Many affected children with organic acidemias experience intellectual disability or delayed development. Succinylacetoacetate appears to function as an oncometabolite (similar in function to succinate, another oncometabolite) as patients with high levels of this compound often develop hepatocellular carcinoma (PMID: 20003495).

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