Glucose fatty acid cycle

Randle PJ The glucose-fatty acid cycle—biochemical aspects. Atherosclerosis Rev 1991 22 183-... 

In pregnancy, there is a sharp increase in the plasma fatty acid level after about 12 hours of fasting, much sooner than in the non-pregnant woman. This may be important in maintaining the plasma glucose level not only for the mother but also the foetus. This maintenance is achieved via the glucose fatty acid cycle (Chapter 16). 

To provide an alternative fuel to glucose during starvation. Indeed, fatty acid oxidation restricts the rate of glucose utilisation, which maintains the blood glucose level, via a regulatory mechanism known as the glucose/ fatty acid cycle (Chapter 16). 

The effects of the glucose/fatty acid cycle and those of the hormones on the cycle, on the regulation of the blood glucose level, can be extended by two further changes in metabolism, (i) Fatty acids are taken up by hver and converted to ketone bodies, which are released... 

Figure 16.3 Effects of insulin on the glucose/fatty acid cycle. Insulin enhances glucose metabolism by stimulating glucose uptake by muscle and adipose tissue and by inhibiting lipolysis in adipose tissue (see Chapter 12 for the mechanism of these effects). The effect of glucose metabolism on lipolysis is via stimulation of fatty acid esterification via glycerol 3-phosphate.

Figure 16.4 Effect of several hormones on the glucose/fatty acid cycle. Catecholamines, glucagon and growth hormone stimulate lipolysis in adipose tissue and hence antagonise the effects of insulin.

Figure 16.5 Effect of malonyl-CoA on the glucose/fatty acid cycle. Malonyl-CoA is an inhibitor of fatty acid oxidation, so that it decreases fatty acid oxidation in muscle and thus facilitates glucose utilisation (See Figure 7.14). Malonyl-CoA is formed from acetyl-CoA via the enzyme acetyl-CoA carboxylase, which is activated by insulin. Insulin therefore has three separate effects to stimulate glucose utilisation in muscle.

Figure 16.6 Extension of the glucose/fatty acid cycle by inclusion of ketone body formation and gluconeogenesis. The liver has three indirect effects on the glucose/fatty acid cycle which help to conserve the blood glucose and maintain its normal level.

The increased oxidation of fatty acids decreases the rate of glucose utilisation and oxidation by muscle, via the glucose/fatty acid cycle, which accounts for some of the insulin resistance in trauma. An additional factor may be the effect of cytokines on the insulin-signalling pathway in muscle. An increased rate of fatty acid oxidation in the liver increases the rate of ketone body production the ketones will be oxidised by the heart and skeletal muscle, which will further reduce glucose utilisation. This helps to conserve glucose for the immune and other cells. 

The Cerebral Glucose-Fatty Acid Cycle Evolutionary Roots, Regulation, and (Patho) physiological Importance Kurt Heininger... 

From this discussion, it follows that the activity of the PDC tends to be directly associated with high rates of ATP turnover or high concentrations of pyruvate, that is, conditions during which the oxidative removal of glucose, lactate, and pyruvate is accelerated. In contrast, PDC activity tends to be inversely associated with diversion of these substrates toward gluconeoge-nesis. A reciprocal relationship exists in some tissues between the oxidation of carbohydrate and long-chain fatty acids that is mediated, in part, by the ratio of phosphorylated/unphos-phorylated PDC. This phenomenon, termed the glucose-fatty acid cycle, is best demonstrable... 

P. J. Randle, P. B. Garland, C. N. Hales, and E. A. Newsholme, The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus, Lancet 1, 785-789 (1963). 

Randle has reviewed his concept of a glucose-fatty acid cycle, with some new experimental material. 5 There has been a recent review of gluconeogenesis, with good current references.The control of phospho-fructokinase, one of the important rate limiting enzymes of glycolysis, is still not fully understood. The activity of the enzyme in mammalian muscle is influenced by substrate concentration and by wiiich can acti-... 

Zhou YP, Grill VE. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 1994 93(2) 870-876. 

The term "caloric homeostasis" was coined by Fredickson and Gordon (1958) to express the joint and complementary roles which free fatty acids and glucose play in the blood in supplying the respiration fuel. The interconversion of carbohydrate and fat has been described by Randle et al. (1963) as the glucose-fatty acid cycle (see Figure 2) Reactions 1 and 2 occurs when there is a surplus of carbohydrate (or of ingested fat). Reaction 3 occurs on fasting. The plasma non-esterified fatty acid... 

Fig. 2 The "glucose fatty acid cycle" according to Randle et al., 1963.

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