Ammonia Glutaminase

Hogstad, S., Svenneby, G., Torgner, I. A. etal. Glutaminase in neurons and astrocytes cultured from mouse brain kinetic properties and effects of phosphate, glutamate, and ammonia. Neurochem. Res. 13 383-388,1988. 

In the 3D structure of GatCAB solved at 2.3 A of resolution, the glutaminase active center and the binding site of the CCA end of tRNA are 30 A apart. The two sites are connected by a channel, mostly hydrophobic in the outside, but lined inside with a succession of alternating strictly conserved positive and negative residues. The structure suggests a proton relay mechanism that carries ammonia from one site to the other by repeated... 

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30-50 mmol per day. In metabolic acidosis (e.g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H"" release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values alkalosis), renal excretion of ammonia is reduced. 

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) is liberated in mitochondria by the enzyme glutaminase. 

Ammonia transport in the blood from the peripheral tissues to the liver occurs by two major mechanisms glutamine can be synthesized from glutamate and ammonia (glutamine synthetase) or pyruvate can be transaminated to alanine. In the liver, the ammonia group is removed from glutamine by glutaminase and from alanine by transamination. 

The glutamine synthase reaction is important in several respects. First, it produces glutamine, one of the 20 major amino acids. Second, in animals, glutamine is the major amino acid found in the circulatory system. Its role is to carry ammonia to and from various tissues, but principally from peripheral tissues to the kidney, where the amide nitrogen is hydrolysed by the enzyme glutaminase (reaction below) this process regenerates glutamate and free ammonium ion, which is excreted in the urine. 

Liver contains both glutamine synthase and glutaminase, but the enzymes are localised in different cellular locations. This ensures that the liver is neither a net producer nor a net consumer of glutamine the difference in cellular location of these two enzymes allows the liver to scavenge ammonia that has not been incorporated into urea. The enzymes of the urea cycle are located in the same cells as the glutaminase. The result of this differential distribution... 

Hypokalaemia Hypokalaemia increases the activity of renal glutaminase, so that more ammonia is formed and transported back via the blood of the renal vein. A lack of potassium in the brain cells is in itself a further cause of serious cerebral dysfunction, (s. fig. 15.2)... 

---