METABOLISM DURING STARVATION

 

INTRODUCTION: In early fasting the effect of short term regulation by altering the activity of existing enzymes also known as, fine control, is more significant. When starvation is prolonged foe example for more than 2 days, long term adaptation sets in. For example, the brain starts metabolising ketone bodies deriving about 30% energy from ketone bodies.

FIRST STAGE: Glycogenolysis: During fasting, at first, blood glucose level is maintained by hepatic glycogenolysis. The glycogen stores are sufficient for about 18 hours. The primary requirement for glucose is to meet the demands of the brain.

SECOND STAGE: Gluconeogenesis: Even before the glycogen stores are depleted, gluconeogenesis is accelerated. The amino acids released from muscle form the major substrate for gluconeogenesis. The amino nitrogen is transferred from other amino acids to pyruvate to form alanine. Thus the amino group reaches the liver as alanine where it is transaminated to give pyruvate for gluconeogenesis. This glucose alanine cycle serves to transport the amino nitrogen of other amino acids to liver in a harmless form. Glutamic acid also serves as an important mode of transport of amino acids to liver. The branched chain amino acids liberated by muscle protein catabolism especially leucine and isoleucine are utilized by the muscle to give energy. Brain can preferentially take up the glucogenic valine from the blood stream.

THIRD STAGE: Lipolysis: The prevailing state of high glucagon-insulin ratio stimulates cAMP mediated lipolysis by increasing the activity of hormone sensitive lipase. Then skeletal muscle, heart and kidney will shut down their glucose utilization; and will depend mainly on fatty acids for energy needs (glucose-fatty acid cycle). Inactivation of pyruvate dehydrogenase by phosphorylation is the basis of this change. The stimulation of the activity of CAT by glucagon favors increased rate of beta oxidation. The increased rate of lipolysis and beta oxidation provides an alternate source of fuel as acetyl CoA and subsequently ketone bodies. Ketone bodies provide fuel for tissues like heart muscle, skeletal muscle and to some extent the brain. It is seen that brain starts utilizing ketone bodies from 3rd day of starvation. By 10th day of starvation about 60% of energy for brain is derived from ketone bodies.

FOURTH STAGE: Acidosis: However, this state cannot continue indefinitely since excessive production of ketone bodies leads to metabolic acidosis. When the bicarbonate buffering capacity is exceeded, the pH falls and hyperventilation occurs as a compensatory mechanism. 

FIFTH STAGE: Death from Starvation: Metabolic acidosis and dehydration, unless corrected efficiently, will lead to death. A normal person has fuel reserves to live up to 45–60 days.

RELATED;

1.  Glycolysis

2.  Gluconeogenesis

3.  BIOCHEMISTRY

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