Renal and hepatic aspects of ketoacidosis: a quantitative analysis based on energy turnover.
The central theme explored is that the rate of ATP production cannot exceed its rate of use in any organ or compartment. Thus the rate of ATP turnover exerts an absolute control over the rates in pathways that synthesize it. This is manifested in two major ways: substrate competition for oxidation and the influence of changes in oxygen consumption rate on the rate of fuel oxidation. By direct measurement, the rate of ketogenesis in the liver is as high as 1500 mmol/day during chronic ketoacidosis of fasting. Given the limited ate of hepatic oxygen consumption, ketogenesis and glucose synthesis from amino acids compete as precursors for hepatic ATP synthesis. Thus There is little room to increase the rate of ketoacid production further in these subjects. Energy turnover considerations in the kidney during chronic fasting seem to limit renal NH4+ production. In this case, there is competition between glutamine and ketone bodies as ATP precursors. This aspect may be important in the regulation of lean body mass catabolism of fasting. There is a "trade-off" in maintaining high circulating ketone body concentrations during fasting. The benefit is primarily for the CNS, and the cost is small loss of lean body mass owing to the need for high rates of NH4+ excretion.
Halperin
M L
ML
Renal Division, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Cheema-Dhadli
S
S
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D007662:Ketosis / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological
D007657:Ketone Bodies