Incorporation

Fluoroacetate. This naturally occurring toxicant is an analogue of acetate and is incorporated into acetylCoA (fluoroacetate) and hence into Krebs' (TCA) cycle as fluorocitrate. This blocks the enzyme aconitase as the fluorine atom cannot be removed. The TCA cycle is blocked and citrate accumulates. The mitochondrial energy supply is disrupted hence cardiac damage occurs. Lack of oxaloacetate will allow ammonia to accumulate leading to convulsions.

Galactosamine. An amino sugar which causes hepatic damage similar to viral hepatitis (non-zonal) and focal necrosis. It may also cause cirrhosis and tumours. It causes inhibition of DNA and protein synthesis. Levels of UTP and UDP-glucose fall and other UDP-hexosamines and acetylhexosamines rise. Galactosamine forms UDP-galactosamine which leads to depletion of UTP so synthesis of RNA and protein are disrupted. Abnormal membrane glycoproteins may be produced leading to membrane damage.

Ethionine. An hepatotoxic analogue of methionine causing fatty liver (accumulation of triglycerides). Chronic exposure causes cirrhosis, bile duct proliferation and heptatocellular carcinoma. It forms S-adenosyl ethionine which traps adenosyl leading to ATP depletion which reduces triglyceride export from the liver. It also leads to ethylated bases in DNA.

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