Muscle transaminase activities

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... 

Oral human LDlq is equal to 221 mgkg Adverse acute reactions to bismuth include acute renal failure following ingestion of excessive concentrations. Bismuth can cause nausea, vomiting, and abdominal pain within hours of exposure. Muscle cramps and weakness, blurred vision, and hyperreflexia may be exhibited. Liver transaminase activities may be elevated. 

A 59-year-old man took troglitazone 400 mg/day for 6 months and alcohol about 40 g/day. He developed weakness and muscle pain. He had mild liver damage. His HbAic concentration was 9.0%. All his muscles were tender, his creatine kinase activity was 10 570 IU/ml, and his myoglobin, aldolase, and aspartate transaminase were raised. Troglitazone was withdrawn. He improved biochemically and clinically. 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

A 75-year-old-man taking simvastatin 80 mg/day and diltiazem 240 mg/day developed extreme weakness and diffuse muscle pain. All drugs were withdrawn and he underwent hemodialysis. Within 3 weeks his muscle pain disappeared and he regained function in his legs. The activities of creatine kinase and transaminases gradually returned to normal, but he continued to need hemodialysis. 

Glucocorticoids also increase the activity of transaminases (aminotransferases), especially in the skeletal muscle. Aminotransferases serve to transfer the amino groups from amino acids to be metabolized to a-keto acids, especially pyruvate. In the latter case, the alanine thus formed is transported from the muscle into the bloodstream and extracted from there by the liver. In the liver, alanine is converted to glucose, and glucose may then return to the muscle as it does in the Cori cycle (Figure 18.4). This is the alanine cycle, and more about this is discussed in Chapter 20. Branched-chain amino acids are the principal donors of nitrogen to pyruvate in the muscle and are thus important actors in the alanine cycle. 

When B. officinalis was mistaken for a similar plant, Securinega suffruticosa, and was cooked in a soup used for muscle aches, lumbago, or as a tonic by 19 patients, 14 developed diarrhea, 10 had nausea and felt cold, nine had sensations of abdominal fullness, and seven vomited (3). Liver enzymes rose and the median times to median peak activities were 3 days for alanine transaminase, 2 days for aspartate transaminase, 5 days for alkaline phosphatase, and 12 days for gamma glutamyltranspeptidase. The liver damage was hepatocellular liver injury rather than cholestatic and marked jaundice did not develop. 

In a report dating from 1987, low selenium concentrations were found in four children receiving long-term parenteral nutrition. There was erythrocyte macrocytosis (n — 3), loss of pigmentation of hair and skin (n = 2), raised transaminase and creatine kinase activities (n — 2), and profound muscle weakness n = 1). Intravenous supplementation with selenium for 3-12 months resulted in progressive improvement in all these (70). 

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... 

Although not completely known, the amino acid sequence of the rabbit muscle aldolase subunit is largely elucidated. (A more detailed description on protein structure appears in the chapter on inborn errors of metabolism.) The molecule contains 364 amino acids with a proline NH2-terminal, a tyrosine in the COOH-terminal position, and 8 cysteine residues. A critical residue is the lysine 221 which is believed to form a Schiff base with dihydroxyacetone phosphate. (The role of Schiff bases in enzymic reactions is discussed in more detail in the section devoted to transaminases.) In the model proposed by Lai und Horecker [51], this lysine is near the center of the molecule. If one follows the contour of the molecule from this critical residue 221, which must be at the active center, toward the tyrosine carboxy terminal, three SH groups are well exposed on the surface of the molecule. They occupy positions 193, 171, and 143. 

Therefore one speaks of a glucose alanine cycle involving the conversion of alanine to pyruvate through the catalytic action of the proper transaminase. If starvation is prolonged, the alanine production in muscle is reduced and gluconeogenesis decreases in spite of the fact that the activities of the liver enzyme remain adequate. 

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