Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured rates of ketogenesis and malonyl-CoA contents of hepatocytes isolated from meal-fed rats under a variety of incubation conditions in order to determine the relationship between the intracellular malonyl-CoA level and the rate of ketogenesis. Evidence obtained from rat liver homogenates suggested that malonyl-CoA, which is a major determinant of fatty acid synthesis in vivo, also inhibits carnitine acyltransferase I (EC 2.3.1.21) and thereby decreases the rate of ketogenesis (McGarry, J.D., Mannaerts, G.P., and Foster, D.W. (1977) J. Clin. Invest. 60, 265-270). In hepatocytes from meal-fed rats, malonyl-CoA could be increased by glucose or lactate plus pyruvate and decreased by glucagon, oleic acid and the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furoic acid. Malonyl-CoA varied from 14.8 +/- 1.2 to 1.4 +/- 0.1 nmol/g wet weight of cells. Rates of ketone body production varied from 0.10 +/- 0.01 to 0.96 +/- 0.06 mumol/min/g wet weight of cells and varied inversely with the malonyl-CoA content. Dixon plots and Cornish-Bowden plots of data suggest that malonyl-CoA is a competitive inhibitor of ketogenesis with a Ki of 2 nmol/g wet weight of cells. We conclude that in hepatocytes from meal-fed rats the cellular content of malonyl-CoA and the concentration of long chain fatty acid available to the cells are major determinants of the rate of ketogenesis.
 ...
PMID:Ketogenesis and malonyl coenzyme A content of isolated rat hepatocytes. 63 84

Hepatocytes were isolated from 3 and 5 month old female genetically obese Zucker rats and their lean littermate controls. An age-dependent loss in sensitivity of fatty acid synthesis to inhibition by both glucagon and dibutyryl cyclic AMP was observed with hepatocytes from the obese rats. Hepatocytes from lean animals were much more sensitive to these agents, regardless of age. Low concentrations of glucagon and dibutyryl cyclic AMP actually produced some stimulation of fatty acid synthesis with hepatocytes prepared from the older obese rats. 5-Tetradecyloxy-2-furoic acid, a compound which inhibits fatty acid synthesis, was a very effective inhibitor of fatty acid synthesis by hepatocytes isolated from all rats used in the study. An inhibition of lactate plus pyruvate accumulation and a strong stimulation of glycogenolysis occurred in response to both glucagon and dibutyryl cyclic AMP with hepatocytes from both age groups of lean and obese rats. The results suggest that with aging of the obese female Zucker rat some step of hepatic fatty acid synthesis becomes progressively less sensitive to inhibition by glucagon and dibutyryl cyclic AMP. This may play an important role in maintenance of obesity in these animals.
 ...
PMID:Age-related decrease in sensitivity to glucagon and dibutyryl cyclic AMP inhibition of fatty acid synthesis in hepatocytes isolated from obese female Zucker rats. 632 93

The development of fatty acid metabolism was studied in isolated hepatocytes from newborn rats. Ketone-body production from oleate is increased 6-fold between 0 and 16 h after birth. This increase is related to an enhanced beta-oxidation rather than to a channeling of acetyl-CoA from the tricarboxylic acid cycle to ketone-body synthesis. The increase in oleate oxidation is not related to a decreased esterification rate, as the latter is already low at birth and does not decrease further. At birth, lipogenic rate is 2-3-fold lower than in fed adult rats and it decreases to undetectable values in 16 h-old rats. A 90% inhibition of lipogenesis in hepatocytes of newborn rats (0 h) by glucagon and 5-(tetradecyloxy)-2-furoic acid does not lead to an increased oxidation of non-esterified fatty acids. This suggests that the inverse relationship between lipogenesis and ketogenesis in the starved newborn rat is not responsible for the switch-on of fatty acid oxidation at birth. Moreover, ketogenesis from octanoate, a medium-chain fatty acid the oxidation of which is independent of carnitine acyltransferase, follows the same developmental pattern at birth as that from oleate.
 ...
PMID:Development and regulation of ketogenesis in hepatocytes isolated from newborn rats. 662 64

To study the binding to mitochondria and the phosphorylation of ATP-citrate lyase (EC 4.1.3.8), isolated rat hepatocytes were fractionated by exposure to digitonin. After incubation of hepatocytes with the hypolipidemic agent 5-(tetradecyloxy)-2-furoic acid, which decreases the cellular CoA, the amount of bound ATP-citrate lyase was increased, but the content of acid-stable phosphate in the enzyme was diminished. Glucagon, in contrast, decreased the amount of bound enzyme but increased phosphorylation. This inverse relationship might indicate either that the bound ATP-citrate lyase is less readily phosphorylated or that the phosphorylated enzyme binds less readily to mitochondria.
 ...
PMID:Influence of glucagon or 5-(tetradecyloxy)-2-furoic acid on binding to mitochondria and phosphorylation of ATP-citrate lyase. 706 84