Ketogenesis/ketones utilization

One suggestion to explain this discrepancy is that two pathways of fat catabolism are available and that ketone body formation is the resultant of only one type of breakdown.177 This latter type, also called the indirect fat utilization, 182 occurs in the liver the catabolism of fat in the muscle, called the -direct method, either involves no ketogenesis or the ketone bodies are immediately utilized and no accumulation occurs. 

Sass JO. Inborn errors of ketogenesis and ketone body utilization. J Inherit Metab Dis. 2012 35(l) 23-8. 

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. 

KBs are necessary to provide energy to the tissues during starvation. Although the liver actively produces KBs, it cannot oxidize them because it lacks thiophorase. Extrahepatic tissues with mitochondria can utilize KBs, including the brain. Acetone is a non-metabolizable side-product of ketogenesis. The pathway of ketone metabolism is shown below. 

When carbohydrates are not available to meet energy needs, the body breaks down fatty acids, which undergo /3-oxidation to acetyl-CoA. Normally, acetyl-CoA would enter the citric acid cycle for further oxidation and energy production. However, when large quantities of fatty acids are degraded, the citric acid cycle cannot utilize the full amount. As a result, acetyl-CoA accumulates in the liver, where acetyl-CoA molecules combine to form compounds called ketone bodies in a pathway known as ketogenesis (see Figure 18.16). 

---