Define regulation of malice enzyme by starvation & refeeding?
ME catalyzes the oxidative decarboxylation of malate to pyruvate and CO2 simultaneously generating the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) From NADP t, much of the NADPH generated by this reaction is utilized in the de novo synthesis of long-chain fatty acids. ME responds to dietary and hormonal manipulation in much the same way as L-PK does. The level of the hepatic enzyme is low in starved animals and high in fed animals, especially if the diet is high in carbohydrate. The concentration of ME is controlled by regulating its synthesis rate which, in turn correlates positively with abundance of ME rn RNA, indicating pretranslational regulation.
A 50- to 100-fold increase in mRNA level is caused by refeeding starved chicks or ducklings; this is accompanied by about a 50-fold increase in transcription of the ME gene. Hormones also play an important role in regulating ME. The concentration of ME is low in diabetic and hypothyroid animals and restored to normal or higher levels by treatment with insulin or T, respectively. Insulin has little effect by itself but amplifies the effect of T3, such that the total increase is 100 to 150-fold.
One fuel that affects ME, apparently independently of insulin, is fructose. As with other lipogenic enzymes, dietary fructose increases the levels of ME and its mRNA even in diabetic animals. Hormones control the synthesis of ME by regulating the abundance of its rn RNA, indicating pretranslational control.
Insulin, glucagon s, glucocorticoids and triiodothyronine (T3) modulate the rate of fatty acid synthesis and the activities of the lipogenic enzymes. Evidence that these hormones are mediators of the effects of diet on hepatic enzyme activities is based on a variety of mainly correlative evidence. The blood of animals fed high-carbohydrate diets has an elevated level of insulin and a decreased level of glucagon s. The opposite is observed in starved animals - lowered insulin and elevated glucagon s. In djabetic animals, insulin levels are low and glucagon s levels high; the rate of Iipogenesis and the activities of the lipogenic enzymes are low. In perfused liver, liver slices and isolated hepatocytes; insulin stimulates and glucagon s inhibits the rate of fatty acid synthesis. Increases in lipogenic flux and activities of the lipogenic enzymes caused by refeeding starved animals are blocked by the simultaneous administration of glucagons. Finally, in hepatocytes in culture, insulin stimulates and glucagon inhibits accumulation of the lipogenic enzymes. These results suggest that insulin and glucagons play important roles in the metabolic transitions between the fed and starved states.
Although, the level of thyroxine is not affected by starvation or feeding, the concentration of the active form of the thyroid hormone T is regulated in a manner similar to that for insulin - decreased in starved animals and increased in fed animals. These results are consistent with a role for T, in the regulation of lipogenic enzyme activity during the transitions between the fed and starved states.