Ketogenic conditions

Of great interest is the fact that under ketogenic conditions (fasting, alloxan diabetes, glucagon treatment) liver mitochondrial carnitine transport is accelerated because of an increased mitochondrial carnitine pool under these conditions, so that the ability of the liver to transport fatty acids into the mitochondria is increased [89]. 

Much evidence, nevertheless, shows that the acceleration of hepatic fatty acid oxidation under ketogenic conditions entails important intracellular adaptive changes at steps subsequent to fatty acid activation. A set of these adaptations enhance the proportion of extramitochondrial fatty acyl-CoA being directed to the mitochondrial oxidative route over that being channeled for triacylglycerol and lipoprotein synthesis. Opposite changes in the... 

Nevertheless, increases in the hepatic content of long chain acyl-CoA and total CoA are known under ketogenic conditions (Kondrup and Grunnet, 1973 Smith, 1978). The possibility that the ATP inhibition of citrate synthase may be involved in promoting ketone body formation in vivo has likewise been considered unlikely (Lopes-Cardozo et al., 1975 Hansford, 1980). 

Answer Lysine and leucine are exclusively ketogenic. These amino acids are degraded entirely to acetyl-CoA and acetoacetyl-CoA, and no parts of their carbon skeletons can be used for glucose synthesis. Leucine is especially common in proteins. Its degradation makes a substantial contribution to ketosis under starvation conditions. 

Fig. 2.2 Ketosis induced hypoxic tolerance. Western Blot protein analysis of HIF-la in cortical brain of diet induced ketotic rats. A threefold upregulation of HIF-la was evident with feeding a ketogenic diet (KG) for 3 weeks during normoxic conditions compared to standard fed (STD). < 0.05, KG vs. STD...

In liver, which has much less carnitine than muscles and heart, the low carnitine concentration becomes a limiting factor for directing fatty acids toward mitochondria for oxidation, especially when the supply of fatty acids is enhanced. Increases in liver carnitine are usually seen under conditions of enhanced ketogenesis (Snoswell and Koundakjian, 1972 Kondrup and Grunnet, 1973 McGarry eta/., 1975, 1978 Williamson, 1979) and an increase in the ketogenic capacity of intact liver In vitro is demonstrable on... 

Building blocks for cholesterol include acetate, acetyl-CoA and acetoacetyl CoA. There are many sources of these metabolites in the body including the tricarboxylic acid cycle (TCA) but also microbial-derived acetate, the main end-product of carbohydrate fermentation in the colon which is converted into acetyl-CoA by acetyl coenzyme A synthetase 1 (AceCSl) in the cytosol. Acetate may also be taken up by mitochondria and converted into acetyl-coA by AceCS2 for respiration through the TCA, especially under ketogenic or fasting conditions. In... 

When patients are in good condition, a ketogenic diet may be considered in order to promote urinary excretion of excess malonate for diagnostic purposes. 

Shifting the metabolic machinery of the body to excessive utilization of fats instead of carbohydrates or a balance of fats and carbohydrates results In the buildup of ketone bodies— acetoacetate, beta-hydroxybutyrate, and acetone—in the blood and their appearance in the urine. This condition is referred to as ketosis, and outwardly noted by the sweetish, acetone odor of the breath. Three circumstances can cause ketosis (1) high dietary intake of fat but low carbohydrate intake as in ketogenic diets (2) diminished carbohydrate breakdown and high mobilization of fats as in starvation or (3) disorders in carbohydrate metabolism as in diabetes melli-tus. Unless ketosis goes unchecked and results in acidosis, it is a normal metabolic adjustment. 

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