Ketogenesis, ketone bodies, ketosis

It is well established that many animal tissues can oxidize ketone bodies (Snapper and Grunbaum, 1927 Wick and Drury, 1941 Williamson and Krebs, 1961), and this has led to the concept that it is a physiological function of ketone bodies to serve as a fuel of respiration when carbohydrate is in short supply (Krebs, 1961). Experiments have shown that increased production of ketone bodies is closely matched by increased utilization (Bates et al., 1968). These authors suggest the sequence of events leading to "physiological ketosis" as a consequence of hormonal interrelationships a low blood sugar concentration causes an increase in adipose tissue lipolysis and a rise in the concentration of free fatty acids in the plasma. This in turn results in an increased rate of ketogenesis in the liver, which is followed by a rise in blood ketone-body concentrations, and an increased rate of peripheral utilization. 

In all types of diabetes, insufficient amounts of glucose are available in the muscle, liver, and adipose tissue. As a result, liver cells synthesize glucose from noncarbohydrate sources and break down fat, elevating the acetyl-CoA level. Excess acetyl-CoA undergoes ketogenesis, and ketone bodies accumulate in the blood. The odor of acetone can be detected on the breath of a person with uncontrolled diabetes who is in ketosis. 

When high levels of acetyl-CoA are present in the cell, they enter the ketogenesis pathway, forming ketone bodies such as acetoac-etate, which cause ketosis and acidosis. 

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