Metabolic Fates of Amino Groups:- Glutamine Transports Ammonia in the Bloodstream
Ammonia is quite toxic to animal tissues (we examine some possible reasons for this toxicity later), and the levels present in blood are regulated. In many tissues, including the brain, some processes such as nucleotide degradation generate free ammonia. In most animals much of the free ammonia is converted to a nontoxic compound before export from the extrahepatic tissues into the blood and transport to the liver or kidneys. For this transport function, glutamate, critical to intra cellular amino group metabolism, is supplanted by L-glutamine. The free ammonia produced in tissues is combined with glutamate to yield glutamine by the action of glutamine synthetase. This reaction requires ATP and occurs in two steps (Fig. 18–8). First, glutamate and ATP react to form ADP and a -glutamyl phosphate intermediate, which then reacts with ammonia to produce glutamine and inorganic phosphate. Glutamine is a nontoxic transport form of ammonia; it is normally present in blood in much higher concentrations than other amino acids. Glutamine also serves as a source of amino groups in a variety of biosynthetic reactions. Glutamine synthetase is found in all organisms, always playing a central metabolic role. In microorganisms, the en zyme serves as an essential portal for the entry of fixed nitrogen into biological systems. (The roles of glutamine and glutamine synthetase in metabolism are further dis cussed in Chapter 22.) In most terrestrial animals, glutamine in excess of that required for biosynthesis is transported in the blood to the intestine, liver, and kidneys for processing. In these tissues, the amide nitrogen is released as ammonium ion in the mitochondria, where the enzyme glutaminase converts glutamine to glutamate and NH+4 (Fig. 18–8). The NH+4 from intestine and kidney is transported in the blood to the liver. In the liver, the ammonia from all sources is disposed of by urea synthesis. Some of the glutamate produced in the glutaminase reaction may be fur ther processed in the liver by glutamate dehydrogenase, releasing more ammonia and producing carbon skeletons for metabolic fuel. However, most glutamate enters the transamination reactions required for amino acid biosyn thesis and other processes. In metabolic acidosis there is an increase in glutamine processing by the kidneys. Not all the excess NH+4 thus produced is released into the bloodstream or converted to urea; some is excreted directly into the urine. In the kidney, the NH4 forms salts with metabolic acids, facilitating their removal in the urine. Bicarbonate produced by the decarboxylation of-ketoglutarate in the citric acid cycle can also serve as a buffer in blood plasma. Taken together, these effects of glutamine metabolism in the kidney tend to counter act acidosis.
FIGURE 18–8 Ammonia transport in the form of glutamine. Excess ammonia in tissues is added to glutamate to form glutamine, a process catalyzed by glutamine synthetase. After transport in the bloodstream, the glutamine enters the liver and NH+4 is liberated in mitochondria by the enzyme glutaminase.
