Clinical Usefulness of Determining Pyruvate Kinase Isoenzymes in Sera and Liver from Patients with Various Diseases

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It has been shown that pyruvate kinase is distributed as isoenzymes in the mammarian tissues. M1 is present in skeletal muscle, heart and in brain; L in liver parenchymal cells; M2 in liver parenchymal as well as in extraparenchymal cells, leucocytes, spleen, adipose tissues, lung, kidney, testis, ovary, tumor tissues and in fetal muscle. The activity of pyruvate kinase (PK) was measured in sera from patients with muscular dystrophy, other muscle diseases, acute myocardial infarction, and liver diseases. This activity was also measured in liver biopsy samples from insuloma, islet cell adenoma and from lipoatrophic diabetes. In Duchenne and Limb girdle type muscular dystrophy, serum PK activity was elevated 28-fold: elevations were found even when serum aldolase and CPK activities were not elevated. In the late stage of progressive muscular dystrophy, the activity tended to diminish, but remained elevated. In acute myocardial infarction, the activity rose within the first three days. Magnitude of this rise (average 7-fold) and duration was similar to the rise of GOT. In acute hepatitis, where serum GOT or GPT activity was mildly elevated, the activity of serum PK was increased by 50%. In one case with chronic active hepatitis, the activity was found to be elevated when measured in fresh serum. In liver cirrhosis, serum PK activity was significantly lowered. In progressive muscular dystrophy and in acute myocardial infarction, serum PK activity was kinetically M1 since a high ratio of PK activity at (0.2mM/2mM) phosphoenolpyruvate and little or no effect with ATP, FDP and alanine were observed. In acute hepatitis, serum PK activity was activated by FDP, and inhibited by ATP and alanine, but ATP inhibition was completely reversed in 15mM MgC12. The mildly elevated serum PK activity in active hepatitis was most likely M2, although further study with electrophoresis would be necessary to confirm this. Pyruvate kinase activity in liver biopsy samples from patient with insuloma exhibited a 2-to 3-fold elevation of the total activity with a high ratio of type L/M, indicating induction of liver PK by a high level of endogenous insulin. These results indicate that determination of serum PK activity is useful for the diagnosis and follow-up of progressive muscular dystrophy, other active muscular diseases, myocardial infarction and liver diseases. As for liver diseases, serum PK activity has to be measured from fresh sera while in muscle and heart diseases, the activity can be measured from stored frozen sera. The determination of pyruvate kinase isozymes in biopsy sample from liver enables us to estimate the metabolic state of the liver concerning glucose metabolism.

Clinical Usefulness of Determining Pyruvate Kinase Isoenzymes in Sera and Liver from Patients with Various Diseases

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