Kidney transaminases

While considerable amounts of both GOT and GPT are found in cardiac muscle, skeletal muscle and kidney, differential diagnosis is aided by the fact that the liver shows a much higher total GPT activity. An important clinical application of measurements of transaminase activity is the detection and diagnosis of viral... 

Baseline serum creatinine, hematology profiles, and serum transaminases with repeat levels at 6- to 12-month intervals are useful in identifying specific toxicities to the kidney, liver, GI tract, or bone marrow. 

Jones TW, Chen Q, Schaeffer V, et al. 1988. Immunohistochemical localization of glutamine transaminase K, a rat kidney cysteine conjugate p-lyase, and the relationship to the segment specificity of cysteine conjugate nephrotoxicity. Mai Pharm 34 621-627. 

Hepatic dysfunction and urinary abnormalities were seen In some subjects after CS exposure at Edgewood. Little is known of the effects of CS on the kidneys and liver. The small proportion of subjects who had abnormal urinalysis (7 of 50 14Z) and high transaminase (3 of 50 6Z) Indicates Idiosyncratic reactions, If the abnormalities were indeed due to CS exposure. The most likely course of idiosyncratic drug-induced, nonfulmlnant hepatitis is complete recovery after removal of the agent. Recurrence of hepatic reactions would be expected on re-exposure to CS If the original transaminase Increases were due to CS. 

In female Sprague-Dawley rats, daily intraperitoneal injections of 10, 30, 50 or 70 mg/kg bw 1,1-dimethylhydrazine resulted in the death of 0,5, 6 and 9 out of 10 animals per group (Cornish Hartung, 1969). Surviving animals showed diuresis, increased serum transaminase levels and histopathological signs of mild kidney damage. 

In addition, Adrian also observed a hypertrophy of the caecum, liver, and kidneys, and a decrease in fertility (20,133) attributed to a certain toxicity or to nutritional deficiencies. Lee et al. (33) observed a hypertrophy of the liver and kidney and an increase of the serum transaminases (GOT and GPT) with Maillard fractions extracted from browned apricots, and Kimiagar et al. (47) observed larger changes in biological parameters after a long-term study with browned egg albumin. 

Apart from hormonal aspects of pseudocholinesterase activity previously dealt with (48,86,107), there have been a number of studies since 1954 showing that cortisone may act on the transaminase activity of various organs (46, 49, 103), particularly liver, heart, and kidneys, which have the highest activity (4,21). In 1957 Gavosto et al. (58) suggested that the hormone may enhance gluconeogenesis by activating the transamination process in the liver. Rosen et al. (104-106) found... 

Induction of extrahepatic mdoleamine dioxygenase (which catalyzes the same reaction as tryptophan dioxygenase, albeit by a different mechanism) by bacterial lipopolysaccharides and mterferon-y may result in the production of relatively large amounts of kynurenine and hydroxykynurenine in tissues that lack the enzymes for onward metabolism. Kidney has kynurenine transaminase activity, and therefore extrahepatic metabolism of tryptophan may result in significant excretion of kynurenic and xanthurenic acids, even when vitamin Bg nutrition is adequate. 

In 25 children with chronic hepatitis C, pretreatment positivity for liver/kidney microsomal type 1 (LKM-1) antibodies was associated with more frequent treatment-limiting increases in serum alanine transaminase activity (256). Withdrawal of interferon alfa-2b because of hypertransaminasemia was required in three of four LKM-1 positive children compared with two of the 21 LKM-1 negative children. Although none developed features of autoimmune hepatitis, careful surveillance of hepatic function is recommended in LKM-l-positive patients. 

Transaminases are widely distributed throughout the body. AST is found primarily in the heart, liver, skeletal muscle, and Iddney, whereas ALT is found primarily in the liver and kidney, with lesser amounts in heart and skeletal muscle (Table 21-2). ALT is exclusively cytoplasmic both mitochondrial and cytoplasmic forms of AST are found in cells. These are genetically distinct isoenzymes with a dimeric structure composed of two identical polypeptide subunits of about 400 amino acid residues. 

Transamination reactions combine reversible amina-tion and deamination, and they mediate redistribution of amino groups among amino acids. Transaminases (aminotransferases) are widely distributed in human tissues and are particularly active in heart muscle, liver, skeletal muscle, and kidney. The general reaction of transamination is... 

Often there is no good clinical test available to determine the exact type of hepatic lesion, short of liver biopsy. There are certain patterns of enzyme elevation that have been identified and can be helpful (Table 38-3). ° The specificity of any serum enzyme depends on the distribution of that enzyme in the body. Alkaline phosphatase is found in the bile duct epithelium, bone, and intestinal and kidney cells. 5-Nucleotidase is more specific for hepatic disease than alkaline phosphatase, because most of the body s store of 5 -nucleotidase is in the liver. Glutamate dehydrogenase is a good indicator of centrolobular necrosis because it is found primarily in centrolobular mitochondria. Most hepatic cells have extremely high concentrations of transaminases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are commonly measured. Because of their high concentrations and easy liberation from the hepato-cyte cytoplasm, AST and ALT are very sensitive indicators of necrotic lesions within the liver. After an acute hepatic lesion is established, it may take weeks for these concentrations to return to normal. ... 

Oxalate, produced from glycine or obtained from the diet, forms precipitates with calcium. Kidney stones (renal calculi) are often composed of calcium oxalate. A lack of the transaminase that can convert glyoxylate to glycine (see Fig 39.6) leads to the disease primary oxaluria type I (PH 1). This disease has a consequence of renal failure attributable to excessive accumulation of oxalate in the kidney. 

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