Summary
Key enzymes of gluconeogenesis in the liver, phosphoenolpyruvate carboxykinase [EC 4.1.1.32] and glucose-6-phosphatase [EC 3.1.3.9], were studied in patients with primary or metastatic hepatic cancer. Liver specimens for enzyme assay were obtained by necropsy performed within four hours after death. It was confirmed that both enzyme activities in rat liver preserved at 4°C remained unchanged within nine hours after the removal of the tissue. Activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase decreased to below ten per cent of the control in neoplastic liver tissue of patients with hepatocellular carcinoma accompanied with liver cirrhosis. These two enzyme activities in cirrhotic tissue of patients with hepatocellular carcinoma were lower than those in patients merely with cirrhosis. In patients with metastatic hepatic cancer both two enzyme activities further decreased and were scarcely detected not only in neoplastic tissue but also in non-neoplastic tissue. These results show that hepatic gluconeogenesis markedly decreases in patients with primary or metastatic hepatic cancer. The biochemical analysis of the blood in hepatic cancer, decreased in blood glucose and release in immunoreactive glucagon, also suggested the supression of gluconeogenesis.
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Scrutton MC, et al: The regulation of glycolysis and gluconeogenesis in animal tissue. Ann Rev Biochem 37: 249, 1968
Hommes FA, et al: Two cases of phosphoenolpyruvate carboxykinase deficiency. Acta Pediatr Scand 65: 233, 1976
Vidnes J, et al: Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycemia. Acta Pediatr Scand 65: 307, 1976
McFadzean AJS, et al: Hypoglycemia in primary carcinoma of the liver. AMA Arch Int Med 98: 720, 1956
McFadzean AJS, et al: Further observations on hypoglycaemia in hepatocellular carcinoma. Am J Med 47: 220, 1969
Gumaa KA, et al: Enzymes and intermediates of the pentose phosphate pathway in liver and hepatomas. Biochim Biophys Acta 158: 300, 1968
Weber G, et al: Operation of pleiotropic control in hormonal regulation and in neoplasia, in “Advances in Enzyme Regulation” Vol XII, Pergamon Press LTD, Oxford. 1974, p 11
Taketa K, et al: Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. II. Human viral hepatitis and cirrhosis of the liver. Enzymes 21: 200, 1976
Hammond KD, et al: Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures. Cancer Res 38: 1317, 1978
Seubert W, et al: On the mechanism of gluconeogenesis and its regulation. II. The mechanism of gluconeogenesis from pyruvate and fumarate. Biochem Z 343: 176, 1965
Nakagawa H, et al: Cold adaptation. I. Effect of coldexposure on gluconeogenesis. J Biochem 69: 923, 1971
Swanson MA, et al: Glucose-6-phosphatase from liver, in “Methods in Enzymology” Vol II. ed by Colowick SP and Kaplan NO. Academic Press Inc. New York. 1955,p 541
Itzhaki RF, et al: A micro-biuret method for estimating proteins. Anal Biochem 9: 401, 1964
Huggett AStG, et al: Use of glucose oxidase, peroxidase, and o-dianisidine in determination of blood and urinary glucose. Lancet II: 368, 1957
Wide L, et al: Radioimmunoassay of proteins with the use of sephadex-coupled antibodies. Biochim Biophys Acta 130: 257, 1966
Block MB, et al: Circulating C-peptide immunoreactivity studies in normals and diabetic patients. Diabetes 21: 1013, 1972
Jogensen KH, et al: Purification of125I-glucagon by anion exchange chromatography. Horm Metab Res 4: 223, 1972
Unger RH, et al: Glucagon antibodies and their use for immunoassay for glucagon. Proc Soc Exp Biol Med 102: 621, 1959
Nordlie RC, et al: Mammalian liver phosphoenolpyruvate carboxykinase activities. J Biol Chem 238: 2259, 1963
Brech W, et al: Studies on pyruvate carboxylase in rat and human liver. Biochim Biophys Acta 201: 145, 1970
Longshaw ID, et al: The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex. J Clin Invest 51: 2277, 1972
Yeung RTT, et al: Hypoglycemia associated with lipid accumulation in primary hepatocellular carcinoma. Cancer 32: 1482, 1973
Unger RH, et al: Glucagon and the insulin: glucagon ratio in diabetes and other catabolic illnesses. Diabetes 20: 834, 1971
Parrilla R, et al: Effect of glucagon: insulin ratios on hepatic metabolism. Diabetes 23: 725, 1974
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Tsubouchi, H., Kamibeppu, A., Fujisaki, K. et al. Hepatic gluconeogenic key enzymes in patients with hepatic cancer. Gastroenterol Jpn 15, 564–569 (1980). https://doi.org/10.1007/BF02773759
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DOI: https://doi.org/10.1007/BF02773759