Biochemical aspects of ketogenesis, a review

Ketogenesis occurs only under certain physiological conditions, the physiological substrate for the process being long chain fatty acids. The condition for ketogenesis arises if the long chain fatty acid levels are high enough to render the liver incapable of metabolising all the acetyl CoA, formed as a result of hepatic oxidation of long chain fatty acids, via the tricarboxylic acid cycle to yield water and carbon dioxide. The state in which unesterified fatty acid levels are high enough to cause ketogenesis can be arrived at if there is a lack of insulin or a condition of starvation. Biochemical regulation, pathological condition and relative levels of ketone bodies are also reviewed. It was found that maximum ketonemia reflects not only increased production but also decreased use. The determination of urine or plasma 3-hydroxybutyrate may be of more importance than a simple urinary test upon ketone bodies in diabetic persons

The effect of acidosis on the renal metabolism of glutamine in the rat

Glutamine is the major source of urinary ammonia and this study examines the metabolism of that amino acid in rats under varying acid-base conditions. Other workers have shown that in acidosis there is enhanced renal oxidation of glutamine, which requires increased amounts of acetyl CoA. The present study has shown that during acidosis there was no change in the activity of oxaloacetate decarboxylase and malic enzyme, two enzymes capable of increasing the formation of acetyl CoA. This study also showed that 3-mercaptopicolinic acid inhibited PEPCK - the rate limiting enzyme of gluconeogenesis - and thereby inhibited ammoniagenesis from glutamine mainly by inhibiting deamination. Metabolic acidosis was induced with NH4C1 or HC1. In rats given NH4C1 there was an immediate increase in blood ammonia levels and urinary excretion of ammonia, but this did not occur with rats fed HC1 which showed no change in urinary ammonia but a decrease in urea excretion. Rats fed either NH4C1 or HC1 had similar increases in the plasma concentrations of glutamine, renal PEPCK activity, ammonia and glucose production by renal cortical slices. The time course of changes in metabolic intermediates was measured in rats given NH4C1 or HC1. NH4C1 caused a striking decrease in renal levels of malate, 2-oxoglutarate and phosphoenol pyruvate. Similar changes were observed with HC1, but in addition the levels of glucose and glucose-6-phosphate were elevated. The results of the studies with 3-mercaptopicolinic acid and the metabolite profile in response to acidosis are both constant with the theory that displacement of the glutamic dehydrogenase equilibrium is an important mechanism in the control of glutamine utilisation and the ammoniagenic response to acidosis (AU)