Glucose oxidation in muscle

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

PPARy activation also leads to decreased expression of gene-encoding enzymes required for gluconeogenesis in the liver and suppressing glucose oxidation in muscle (150,... 

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

Figure 16.2 Redprocal relationship between the changes in the concentrations of glucose and fatty adds in blood during starvation in adult humans. As the glucose concentration decreases, fatty acids are released from adipose tissue (for mechanisms see Figure 16.4). The dotted line is an estimate of what would occur if fatty acid oxidation did not inhibit glucose utilisation. Such a decrease occurs if fatty acid oxidation in muscle is decreased by specific inhibitors.

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.

The absence of ketone bodies is due to the fact that the liver, the source of blood-ketone bodies, cannot oxidize fatty acids to produce acetyl CoA. Moreover, because of the impaired fatty acid oxidation, the liver becomes more dependent on glucose as an energy source. This dependency results in a decrease in gluconeogenesis and a drop in blood-glucose levels, which is exacerbated by the lack of fatty acid oxidation in muscle and a subsequent increase in glucose uptake from the blood. 

The fat cell also has the capabihty of producing at least one hormone that improves insulin sensitivity adiponectin. This factor is made in decreasing amounts as an individual becomes more obese. In animal models, adiponectin decreases hepatic glucose production and increases fatty acid oxidation in muscle. ... 

Lactate, a product of glucose catabolism in oxygen-starved muscles, can be converted into pyruvate by oxidation. What coenzyme do you think is needed Write the equation in the normal biochemical format using a curved arrow. 

In starvation, glucose must be ptovided for the brain and erythrocytes initially, this is supphed from hver glycogen reserves. To spare glucose, muscle and other tissues reduce glucose uptake in response to lowered insuhn secretion they also oxidize fatty acids and ketone bodies preferentially to glucose. 

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