Harpers

244 / CHAPTER 29of amino groups to pyruvate (forming alanine) or to α-ketoglutarate (forming glutamate) (Figure 29–4). Eachaminotransferase is specific for one pair of substratesbut nonspecific for the other pair. Since alanine is also asubstrate for glutamate aminotransferase, all the aminonitrogen from amino acids that undergo transaminationcan be concentrated in glutamate. This is importantbecause L-glutamate is the only amino acid thatundergoes oxidative deamination at an appreciable ratein mammalian tissues. The formation of ammoniafrom α-amino groups thus occurs mainly via the α-amino nitrogen of L-glutamate.Transamination is not restricted to α-amino groups.The δ-amino group of ornithine—but not the ε-aminogroup of lysine—readily undergoes transamination.Serum levels of aminotransferases are elevated in somedisease states (see Figure 7–11).L-GLUTAMATE DEHYDROGENASEOCCUPIES A CENTRAL POSITIONIN NITROGEN METABOLISMTransfer of amino nitrogen to α-ketoglutarate forms L-glutamate. Release of this nitrogen as ammonia is thencatalyzed by hepatic L-glutamate dehydrogenase(GDH), which can use either NAD + or NADP + (Figure29–5). Conversion of α-amino nitrogen to ammoniaby the concerted action of glutamate aminotransferaseand GDH is often termed “transdeamination.”Liver GDH activity is allosterically inhibited by ATP,GTP, and NADH and activated by ADP. The reactioncatalyzed by GDH is freely reversible and functions alsoin amino acid biosynthesis (see Figure 28–1).NAD(P) + NAD(P)H + H +L-GlutamateNH 3α-KetoglutarateFigure 29–5. The L-glutamate dehydrogenase reaction.NAD(P) + means that either NAD + or NADP + canserve as co-substrate. The reaction is reversible but favorsglutamate formation.drogen peroxide (H 2 O 2 ), which then is split to O 2 andH 2 O by catalase.Ammonia Intoxication Is Life-ThreateningThe ammonia produced by enteric bacteria and absorbedinto portal venous blood and the ammonia producedby tissues are rapidly removed from circulationby the liver and converted to urea. Only traces (10–20µg/dL) thus normally are present in peripheral blood.This is essential, since ammonia is toxic to the centralnervous system. Should portal blood bypass the liver,systemic blood ammonia levels may rise to toxic levels.This occurs in severely impaired hepatic function or thedevelopment of collateral links between the portal andsystemic veins in cirrhosis. Symptoms of ammonia intoxicationinclude tremor, slurred speech, blurred vision,coma, and ultimately death. Ammonia may betoxic to the brain in part because it reacts with α-ketoglutarateto form glutamate. The resulting depleted levelsof α-ketoglutarate then impair function of the tricarboxylicacid (TCA) cycle in neurons.Amino Acid Oxidases Also RemoveNitrogen as AmmoniaWhile their physiologic role is uncertain, L-amino acidoxidases of liver and kidney convert amino acids to anα-imino acid that decomposes to an α-keto acid withrelease of ammonium ion (Figure 29–6). The reducedflavin is reoxidized by molecular oxygen, forming hy-RNH 3+CHCO –Oα-Amino acidFlavinAMINO ACIDOXIDASEFlavin-H 2+NH 2C O –R COα-Imino acidH 2 O+NH 4Pyruvateα-Amino acidL-Alanineα-Keto acidα-Ketoglutarateα-Amino acidL-Glutamateα-Keto acidFigure 29–4. Alanine aminotransferase (top) andglutamate aminotransferase (bottom).CATALASEH 2 O 2 O 2H 2 O1 /2O 2ROCCOα-Keto acidFigure 29–6. Oxidative deamination catalyzed byL-amino acid oxidase (L-α-amino acid:O 2 oxidoreductase).The α-imino acid, shown in brackets, is not astable intermediate.O –