Occupies A Central Position In Nitrogen Metabolism

Transfer of amino nitrogen to a-ketoglutarate forms L-glutamate. Release of this nitrogen as ammonia is then catalyzed by hepatic L-glutamate dehydrogenase (GDH), which can use either NAD+ or NADP+ (Figure 29-5). Conversion of a-amino nitrogen to ammonia by the concerted action of glutamate aminotrans-ferase and GDH is often termed "transdeamination." Liver GDH activity is allosterically inhibited by ATP, GTP, and NADH and activated by ADP. The reaction catalyzed by GDH is freely reversible and functions also in amino acid biosynthesis (see Figure 28-1).

L-Glutamate a-Ketoglutarate

Figure 29-5. The L-glutamate dehydrogenase reaction. NAD(P)+ means that either NAD+ or NADP+ can serve as co-substrate. The reaction is reversible but favors glutamate formation.

drogen peroxide (H2O2), which then is split to O2 and H2O by catalase.

Ammonia Intoxication Is Life-Threatening

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10-20 |g/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-keto-glutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tri-carboxylic acid (TCA) cycle in neurons.

Amino Acid Oxidases Also Remove Nitrogen as Ammonia

While their physiologic role is uncertain, L-amino acid oxidases of liver and kidney convert amino acids to an a-imino acid that decomposes to an a-keto acid with release of ammonium ion (Figure 29-6). The reduced flavin is reoxidized by molecular oxygen, forming hy-

Pyruvate a-Amino acid

L-Alanine a-Keto acid a-Ketoglutarate L-Glutamate

a-Amino acid a-Keto acid

Figure 29-4. Alanine aminotransferase (top) and glutamate aminotransferase (bottom).

II O

a-Amino acid

AMINO ACID OXIDASE

Flavin Flavin-H2

H2O2

V2O'

Flavin Flavin-H2

a-Imino acid y H2O

a-Keto acid

Figure 29-6. Oxidative deamination catalyzed by L-amino acid oxidase (L-a-amino acid:O2 oxidoreduc-tase). The a-imino acid, shown in brackets, is not a stable intermediate.

nh2+

nh4+

Glutamine Synthase Fixes Ammonia as Glutamine

Formation of glutamine is catalyzed by mitochondrial glutamine synthase (Figure 29-7). Since amide bond synthesis is coupled to the hydrolysis of ATP to ADP and P;, the reaction strongly favors glutamine synthesis. One function of glutamine is to sequester ammonia in a nontoxic form.

Glutaminase & Asparaginase Deamidate Glutamine & Asparagine

Hydrolytic release of the amide nitrogen of glutamine as ammonia, catalyzed by glutaminase (Figure 29-8), strongly favors glutamate formation. The concerted action of glutamine synthase and glutaminase thus catalyzes the interconversion of free ammonium ion and glutamine. An analogous reaction is catalyzed by L-as-paraginase.

Formation & Secretion of Ammonia Maintains Acid-Base Balance

Excretion into urine of ammonia produced by renal tubular cells facilitates cation conservation and regulation of acid-base balance. Ammonia production from intracellu-lar renal amino acids, especially glutamine, increases in metabolic acidosis and decreases in metabolic alkalosis.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook


Post a comment