Gluconeogenesis from amino acids

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

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.

When the blood glucose level falls and the liver s glycogen reserves are also exhausted, the liver still has the capacity to synthesize glucose via gluconeogenesis from amino acids that are supplied from protein breakdown. Under starvation conditions the liver forms increasing amounts of ketone bodies (see fig. 18.7). This is due to elevated concentrations of acetyl-CoA, which favor the formation of ketone bodies. The ketone bodies are secreted and used as a source of energy by other tissues, especially those tissues like the brain that cannot catabolize fatty acids directly. 

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). 

Cortisol, released in response to a variety of stressors (including low blood glucose), stimulates gluconeogenesis from amino acids and glycerol in the liver, thus raising blood glucose and counterbalancing the effects of insulin. 

Corticosterone has a marked effect on protein catabolism, and glucagon promotes gluconeogenesis from amino acids and may regulate the increased use of protein after 30—40 days of fasting. 

Stewart C R, Beevers H 1967 Gluconeogenesis from amino acids in germinating castor bean endosperm and its role in transport to the embryo. Plant Physiol 42 1587-1595... 

As discussed in section 5.4.4.2 and section 9-3.2, many of the products of amino acid metabolism can also be used for gluconeogenesis, as they are sources of pyruvate or one of the intermediates in the citric acid cycle, and hence give rise to oxaloacetate. The requirement for gluconeogenesis from amino acids in order to maintain a supply of glucose explains why there is often a considerable loss of muscle in prolonged fasting or starvation, even if there are apparently adequate reserves of adipose tissue to meet energy needs. 

Gluconeogenesis from Amino Acids. The pathway described above has a general significance beyond the utilization of lactate. We have mentioned previously that many amino acids can be converted to glucose, provided that they give rise to C4-dicarboxylic acids. These acids are members of the citrate cycle and thus can easily produce oxaloacetate and then phosphoenolpyruvate by Utter s reaction. 

It may appear peculiar that build-up and breakdown proceed largely via the same route merely a few key reactions differ. These key reactions are probably the targets of the cell s regulatory mechanism, which must determine the direction that the processes are to take. Gluconeogenesis from amino acids (i.e. ultimately out of proteins), for example, is strongly stimulated by the hormone cortisol (cf. Chapt. XX-2). Such regulation is of decisive importance for the organism s over-all metabolism. 

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