Starvation gluconeogenesis during

Proteolysis also provides carbon skeletons for gluconeogenesis. During starvation, degraded proteins are not replenished and serve as carbon sources for glucose synthesis. Initial sources of protein are those that turn over rapidly, such as proteins of the intestinal epithelium and the secretions of the pancreas. Proteolysis of muscle protein provides some of three-carbon precursors of glucose. However, survival for most animals depends on being able to move rapidly, which requires a large muscle mass, and so muscle loss must be minimized. 

Dietary proteins are a source of amino acids which can serve as important precursors for gluconeogenesis. During a fast or starvation, a major contribution is made by alanine which is released along with other amino acids from skeletal muscle. Since labile proteins rich in alanine are not present in muscle, the released alanine appears to result from the activity of alanine aminotransferase (Section 16.1) which produces alanine from pyruvate. This is the basis of the alanine cycle which also operates between skeletal muscle and the liver. The alanine cycle functions only when peripheral tissues reoxidize glycolytic NADH through the oxidative phosphorylation pathway. In the presence of oxygen, pyruvate is not utilized in lactate production and is available for the amino transfer reaction. 

Proteolysis of muscle during starvation supplies amino acids for gluconeogenesis. 

Figure 16.11 Pattern of fuel utilisation during prolonged starvation. The major metabolic change during this period is that the rates of ketone body formation and their utilisation by the brain increases, indicated by the increased thickness of lines and arrows. Since less glucose is required by the brain, gluconeogenesis from amino acids is reduced so that protein degradation in muscle is decreased. Note thin line compared to that in Figure 16.9.

During periods of hunger, muscle proteins serve as an energy reserve for the body. They are broken down into amino acids, which are transported to the liver. In the liver, the carbon skeletons of the amino acids are converted into intermediates in the tricarboxylic acid cycle or into acetoacetyl-CoA (see p. 175). These amphibolic metabolites are then available to the energy metabolism and for gluconeogenesis. After prolonged starvation, the brain switches to using ketone bodies in order to save muscle protein (see p. 356). 

During periods of starvation, the brain after a certain time acquires the ability to use ketone bodies (see p. 312) in addition to glucose to form ATP. In the first weeks of a starvation period, there is a strong increase in the activities of the enzymes required for this in the brain. The degradation of ketone bodies in the CNS saves glucose and thereby reduces the breakdown of muscle protein that maintains gluconeogenesis in the liver during starvation. After a few weeks, the extent of muscle breakdown therefore declines to one-third of the initial value. 

When food intake decreases, the utilization of fat and protein reserves in the body enables various essential metabolic processes to continue during the nutritional inadequacy. In the early stage of fasting or starvation, glucose requirements of the brain and nervous system are fulfilled by mobilization of glycogen in the liver. This short-term adaptation lasts only a day until glycogen stores are exhausted. Gluconeogenesis... 

In addition to being synthesized or produced by the hydrolysis of dietary protein, amino acids can come from hydrolysis of tissue proteins, e.g., intestinal mucosa or, during starvation, muscle. Amino acids are used in protein synthesis (Chap. 17) they also enter gluconeogenesis and lipogenesis are degraded to provide energy and are used for synthesizing compounds such as purines, pyrimidines, porphyrins, epinephrine and creatine. 

Reviews by Ruderman (19) and Adibi (20,21) indicate that the branched-chain amino acids, particularly leucine, have an important role along with alanine in gluconeogenesis. Leucine and the other two branched-chain amino acids are catabolized in skeletal muscle. The nitrogen that is removed from the branched-chain amino acids in skeletal muscle is combined with pyruvate and returned to the liver as alanine. In the liver the nitrogen is removed for urea production and the carbon chain is utilized as substrate for synthesis of glucose. Adibi et al. (22) reported that during the catabolic conditions of starvation, oxidation of leucine and fatty acids increases in skeletal muscles. While glucose oxidation is reduced, the capacity for oxidation of the fatty acid palmltate more than doubled, and leucine oxidation increased by a factor of six. 

Muscle pyridoxal phosphate is released into the circulation (as pyridoxal) in starvation as muscle glycogen reserves are exhausted and there is less requirement for glycogen phosphorylase activity. Under these conditions, it is potentially available for redistribution to other tissues, especially the liver and kidneys, to meet the increased requirement for gluconeogenesis from amino acids (Black et al., 1978). However, during both starvation and prolonged bed rest, there is a considerable increase in urinary excretion of 4-pyridoxic acid, suggesting that much of the vitamin Be released as a result of depletion of muscle glycogen and atrophy of muscle is not redistributed, but rather is ca-tabolized and excreted (Cobum et al., 1995). 

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