GLUCOSE ALANINE CYCLE

We have learned in the preceding section how the amino group of most amino acid are transferred to a-ketoglutarate generation glutamate. the oxidation deamination of glutamate yields ammonia which in blood/cell is toxic to cellular component at physiological ph.  ammonia exists as ammonium (ammonia nitrate  ions )ammonia produced from extra hepatic tissues such as muscles and other tissue (except muscle) is transported to the liver in the form of alanine and glutamine ,respectively.

In most tissue (except muscle and liver),glutamate is converted into glutamine by glutamine synthesis ("synthetase" are enzyme that utilize ATP for synthesis of new bonds). glutamine is a non toxic neutral compound which can readily cross the lipid membrane .it is carried through blood circulation to the liver.

In muscle ammonia produced by amino acid degradation (transamination and  deamination is converted into glutamate by muscle glutamate dehydrogenase enzyme this enzyme is different from the hepatic glutamate dehydrogenase which removes ammonia from glutamate) next pyruvate (from glycolysis) is transaminated to alanine by alanine amino transaminase . alanine released into blood is picked up by the liver where pyruvate is reformed by reversal of alanine amino transferase reaction there by forming glutamate as the other product .the two product will now be processed independently. the entire process of converting glucose into alanine (in muscle )and then back to glucose (in the liver cells)is known as glucose -alanine cycle.

In the liver pyruvate is converted to glucose and released into circulation for use by muscle and other tissue. the nitrogen coming from different amino acids is deaminated by hepatic glutamate dehydrogenases (GDH) .similarly glutamine transported from other extrahepatic tissue (expert muscle )is first acted upon by mitochondria glutaminase producing glutamate and ammonia the former is oxidatively deaminated .ammonia released in the liver mitochondria is fed the urea cycle for detoxification.

Urea Cycle

free ammonia is toxic to cell so it is detoxified prior to excretion. the normal concentration of ammonia in human plasma is 25-40 mol/l .in ureotelic organism ,urea is the final product of protein /amino acid catabolism. about 90%of the nitrogen excreted in urine is in from of urea. urea cycle was first metabolism cycle to be elucidated by Hans Adolf krebs and his medical student associated kurt Henseleit (1932).

it is also known as krebs -henseleit cycle.

Urea cycle operates in the liver. in this cycle two out of total five enzymes are present in mitochondria and rest are in the cytoplasm. 

in the addition these enzyme , specific transporters assist in the mitochondria uptake of ornithine and release of l-cirtrulline  and transport of aspartate  and glutamate.

the enzyme that catalyse the first four reaction of the urea cycle are also present in kidney  and intestial mucosa where they are involved in arginine biosynthesis. the detoxification of ammonia to urea is energy consuming (4 high energy phosphate bonds utilized synthesized )and entry to the cycle is regulated at. the net reaction of urea synthesis is;

 

The first step of urea cycle is catalyze by carbamoyl phosphate synthetase it is the rate limiting steps of the cycle and bring