Harpers

258 / CHAPTER 30HOHONH 2OCNH 3+NCH 2births). Elevated blood phenylalanine may not be detectableuntil 3–4 days postpartum. False-positives inpremature infants may reflect delayed maturation of enzymesof phenylalanine catabolism. A less reliablescreening test employs FeCl 3 to detect urinaryphenylpyruvate. FeCl 3 screening for PKU of the urineCH3-HydroxykynurenineXanthurenateHONH 4+Figure 30–16. Formation of xanthurenate in vitaminB 6 deficiency. Conversion of the tryptophan metabolite3-hydroxykynurenine to 3-hydroxyanthranilate is impaired(see Figure 30–15). A large portion is thereforeconverted to xanthurenate.COCOO –O –of newborn infants is compulsory in the United Statesand many other countries.Lysine. Figure 30–14 summarizes the catabolism oflysine. Lysine first forms a Schiff base with α-ketoglutarate,which is reduced to saccharopine. In one formof periodic hyperlysinemia, elevated lysine competitivelyinhibits liver arginase (see Figure 29–9), causinghyperammonemia. Restricting dietary lysine relieves theammonemia, whereas ingestion of a lysine load precipitatessevere crises and coma. In a different periodic hyperlysinemia,lysine catabolites accumulate, but even alysine load does not trigger hyperammonemia. In additionto impaired synthesis of saccharopine, some patientscannot cleave saccharopine.Tryptophan. Tryptophan is degraded to amphibolicintermediates via the kynurenine-anthranilatepathway (Figure 30–15). Tryptophan oxygenase(tryptophan pyrrolase) opens the indole ring, incorporatesmolecular oxygen, and forms N-formylkynurenine.An iron porphyrin metalloprotein that is induciblein liver by adrenal corticosteroids and bytryptophan, tryptophan oxygenase is feedbackinhibitedby nicotinic acid derivatives, includingNADPH. Hydrolytic removal of the formyl group ofN-formylkynurenine, catalyzed by kynurenine formylase,produces kynurenine. Since kynureninase requirespyridoxal phosphate, excretion of xanthurenate(Figure 30–16) in response to a tryptophan load is diagnosticof vitamin B 6 deficiency. Hartnup disease reflectsimpaired intestinal and renal transport of tryptophanand other neutral amino acids. Indole derivativesof unabsorbed tryptophan formed by intestinal bacteriaare excreted. The defect limits tryptophan availabilityfor niacin biosynthesis and accounts for the pellagralikesigns and symptoms.COO –COO –+ H3 N C H+ H3 N C HCH 2CH 2P P PH 2 OP i + PP iCH 2CH 2S +CH 3CH 2 AdenineORiboseL-METHIONINEADENOSYLTRANSFERASE+ S CH 2 AdenineCH 3ORiboseHOOHHOOHL-MethionineATPS-Adenosyl-L-methionine(“active methionine”)Figure 30–17. Formation of S-adenosylmethionine. ~CH 3 represents the highgroup transfer potential of “active methionine.”