Starvation intermediate

On the basis of the resnlts with the obese, starvation can be divided arbitrarily into five phases the postabsorptive period, early starvation, intermediate starvation, prolonged starvation and, finally, the premortal period. Although these are characterised by different metabolic patterns, the transition from one period to another is gradnal. Some of the changes in the postabsorptive period and early starvation are described elsewhere in this book bnt they are bronght together in this chapter for completeness. 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

There is no clear-cut division between intermediate and prolonged starvation but after about three weeks the following will apply ... 

The rise in blood ketone bodies continues during intermediate and prolonged starvation. After about 20 days the concentration reaches a plateau at about 8 mmol/L, mostly hydroxybutyrate (Figure 16.10). 

Sequence of metabolic changes from intermediate starvation to death... 

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). 

Healthy, well-nourished individuals produce ketone bodies at a relatively low rate. When acetyl-CoA accumulates (as in starvation or untreated diabetes, for example), thiolase catalyzes the condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the parent compound of the three ketone bodies The reactions of ketone body formation occur in the matrix of liver mitochondria. The six-carbon compound /3-hydroxy-/3-methylglutaryl-CoA (HMG-CoA) is also an intermediate of sterol biosynthesis, but the enzyme that forms HMG-CoA in that pathway is cytosolic. HMG-CoA lyase is present only in the mitochondrial matrix. 

Similarly, amino acids that produce tricarboxylic acid (TCA) cycle intermediates (Chapter 15) produce alanine by conversion to oxaloacetate. During starvation or intake of a carbohydrate-poor diet, conversion of pyruvate to alanine is preferred because pyruvate dehydrogenase is inactivated by oxidation of fatty acids and ketone bodies (Chapters 13 and 18). 

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