Portal de Periódicos da CAPES

Ketogenesis and its regulation

1976; Elsevier BV; Volume: 61; Issue: 1 Linguagem: Inglês

10.1016/0002-9343(76)90024-3

1555-7162

Julie McGarry, Daniel W. Foster,

Pancreatic function and diabetes

The ketotic state has been of major interest to biochemists, physiologists and clinicians for many years.It is our purpose here to review recent advances that provide new insights into the mechanisms by which ketogenesis is regulated.To this end, we shall briefly discuss current understanding of the biochemical physiology of ketogenesis, the hormonal induction of ketosis and clinical implications.THE BIOCHEMICAL PHYSIOLOGY OF KETOGENESIS It is now clear that enhanced production of ketone bodies in the intact organism requires changes in the metabolic patterns of both adipose tissue and liver.The substrate for acetoacetate and o-hydroxybutyrate synthesis by the liver is long chain fatty acids.The latter are readily provided from triglycerides stored in adipose tissue through the operation of a hormone-sensitive lipase [l] which is activated in conditions such as starvation, exercise and uncontrolled diabetes.The released free fatty acids (and glycerol) are transported via plasma to the liver and other tissues.In the liver the incoming fatty acids have essentially two fates.They may be esterified to form triglycerides (for storage or release in very low density lipoprotein particles) or they may be oxidized [ 2-41.Partitioning between the two pathways determines the rate of ketogenesis.If the rate of fatty acid oxidation is high, overproduction of ketones results.The important point is that rapid rates of fatty acid oxidation (and ketogenesis) do not passively follow the increased delivery of free fatty acids to the liver: direct activation of the oxidative sequence is also required.Evidence for this conclusion has been discussed elsewhere [5].