Gluconeogenesis from lactate

After a period of intense muscular activity, the individual continues breathing heavily for some time, using much of the extra 02 for oxidative phosphorylation in the liver. The ATP produced is used for gluconeogenesis from lactate that has been carried in the blood from the muscles. The glucose thus formed returns to the muscles to replenish their glycogen, completing the Cori cycle (Fig. 23-18 see also Box 15-1). 

Which one of the following is characteristic of low insulin levels A. Increased glycogen synthesis B. Decreased gluconeogenesis from lactate C. Decreased glycogenolysis D. Increased formation of 3-hydroxybutyrate E. Decreased action of hormone-sensitive lipase Correct answer = D. 3-hydroxybutyrate—a ketone body—synthesis is enhanced in the liver by taw insulin levels, which favor activation of hormone-sensitive lipase and release of fatty acids from adipose tissue. Glycogen synthesis is decreased, whereas gluconeogenesis is increased. 

Microsomal oxidation yields hypoglycaemic toxin (Dehydrotremetone inactive) [toxin blocks gluconeogenesis from lactate —> plasma acidosis, sweating, tremor, death]... 

Alcohol taken in excess tends to prevent gluconeogenesis from lactate in the liver, because oxidation of ethanol to acetaldehyde competes for the NAD" that is necessary for the conversion of lactate to pyruvate. Severe acidosis, such as diabetic ketoacidosis, may suppress lactate conversion and cause a shift in the lactate-pyruvate equilibrium with the accumulation of H. This shift may, in part, be responsible for the lactic acidosis seen in diabetics. 

Gluconeogenesis from lactate requires six high-energy phosphates, whereas glycolysis only produces a net of two high-energy phosphates. 

Many hours after a meal, and also during starvation, glucose is removed from the blood by muscle and other tissues, and lactate is produced by them. This leads to an increase in the rate of gluconeogenesis from lactate by hepatocytes. The glucose that is produced this way, however, only constitues recycling of the carbon atoms and gluconeogenic enzymes also convert other 3-carbon compounds into glucose. 

Secondly, the transport inhibitor must be able to pass the cell membrane. The inability of benzene-1,2,3-tricarboxylate to inhibit gluconeogenesis from lactate in perfused pigeon liver, a tissue in which mitochondrial efflux of phosphoenolpyruvate is obligatory for glucose synthesis, is presumably due to lack of penetration through the plasma membrane [16], This observation is interesting since it shows that the ability of an inhibitor to penetrate the cell membrane may vary from tissue to tissue benzene-1,2,3-tricarboxylate does inhibit lipogenesis in hepatocytes of neonatal chicks, as discussed above. Another example is the apparent relative impermeability of the plasma membrane of isolated foetal rat hepatocytes, as compared with that from adult rats, for atractyloside, the inhibitor of the adenine nucleotide translocator [17]. 

Mitochondrial aspartate efflux is important in processes like urea synthesis [90], gluconeogenesis from lactate and the transport of cytosolic reducing equivalents to the mitochondria via the so-called malate-aspartate shuttle, e.g. during ethanol oxidation and gluconeogenesis from reduced substrates like glycerol, sorbitol, and xylitol [4,5]. During gluconeogenesis from lactate oxaloacetate is transported to the cytosol as aspartate to circumvent the low permeability of the mitochondrial membrane for oxaloacetate. 

For example, gluconeogenesis from lactate, pyruvate, fructose, and alanine in perfused livers from starved adrenalectomized rats was compared with gluconeogenesis in nonadrenalectomized rats. In two laboratories in which gluconeogenesis from pyruvate and lactate was investigated, opposite results were obtained. One laboratory claimed that adrenalectomy decreased gluconeogenesis, while the other could not demonstrate such an effect. 

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