Essential pentosuria occurs due to defect in the metabolic pathway of
Ans. a (Uronic acid) (Ref. Harper's, Biochemistry, 26th ed., 105, 163, 170; 27th/ 177; H-18th/Table 364-1)ESSENTIAL PENTOSURIA# In liver, the uronic acid pathway catalyzes the conversion of glucose to glucuronic acid, ascorbic acid, and pentoses.# It is also an alternative oxidative pathway for glucose, but--like the pentose phosphate pathway--it does not lead to the generation of ATP.# Glucuronic acid is synthesized from glucose via the uronic acid pathway, which is of major significance for the excretion of metabolites and foreign chemicals (xenobiotics) such as glucuronides. A deficiency in this pathway leads to essential pentosuria.# In this rare hereditary disease, considerable quantities of L-xylulose appear in the urine because of absence of the enzyme necessary to reduce L-xylulose to xylitol. Parenteral administration of xylitol may lead to oxalosis, involving calcium oxalate deposition in brain and kidneys.# Various drugs markedly increase the rate at which glucose enters the uronic acid pathway.- For example, administration of barbital or of chlorobutanol to rats results in a significant increase in the conversion of glucose to glucuronate, L-gulonate, and ascorbate.ESSENTIAL FRUCTOSURIA# The lack of one enzyme of the pathway (gulonolactone oxidase) in primates and some other animals explains why ascorbic acid is a dietary requirement for humans but not most other mammals.# Deficiencies in the enzymes of fructose and galactose metabolism lead to essential fructosuria and the galactosemias.INHERITED DISORDERS OF AMINO ACID METABOLISMAmino acid(s)ConditionEnzyme DefectClinical FindingsInheritancePhenylalaninePhenylketonuriaPhenylalanine hydroxylaseMental retardation, microcephaly, hypopigmented skin and hairs, eczema, "mousy" odorAR DHPR deficiency hyperphenylalaninemiaDihydropteridine reductaseMental retardation, hypotonia, spasticity, myoclonusAR PTS deficiency hyperphenylalaninemia6-Pyruvoyl-tetrahydropterinsynthaseDystonia, neurologic deterioration, seizures, mental retardationAR GCH1 deficiency hyperphenylalaninemiaGTP cyclohydrolase 1Mental retardation, seizures, dystonia, temperature instabilityAR Carbinolamine dehydratase deficiencyPterin-4-carbinolaminedehydrataseTransient hyperphenylalaninemia (benign)ARTyrosineTyrosinemia type I (hepatorenal)Fumary -lacetoacetatehydrolaseLiver failure, cirrhosis, rickets, failure to thrive, peripheral neuropathy, "boiled cabbage" odorAR Tyrosinemia type II (oculocutaneous)Tyrosine transaminasePalmoplantar keratosis, painful corneal erosions with photophobia, mental retardation (?)AR Tyrosinemia type III4-HydrophenylpyruvateDioxygenaseHypertyrosinemia with normal liver function, occasional mental delayAR Hawkinsinuria4-Hydroxyphenylpyruvate DioxygenaseTransient failure to thrive, metabolic acidosis in infancyAD AlkaptonuriaHomogentisic acid oxidaseOchronosis, arthritis, cardiac valve involvement, coronary artery calcificationAR Albinism(oculocutaneous)TyrosinaseHypopigmentation of hair, skin, and optic fundus; visual loss; photophobiaAR Albinism (ocular)Different enzymes or transportersHypopigmentation of optic fundus, visual lossAR, XL DOPA-responsive DystoniaTyrosine hydroxylaseRigidity, truncal hypotonia, tremor, mental retardationARGABA4-Hydroxybutyric AciduriaSuccinic semialdehyde dehydrogenaseSeizures, mental retardation, ataxiaARTryptophanKynurenic aciduriaKynurenine-3-monooxygenaseNiacin deficiency, pellagra, colitisAR Hydroxykynureninuria(xanthurenic aciduria)KynureninaseNiacin deficiency, mental retardation, spasticityARHistidineHistidinemiaHistidine-ammonia lyaseBenignAR Urocanic aciduriaUrocanaseBenignAR Formiminoglutamic aciduriaFormi mi notransferaseOccasional mental retardationARGlycineGlycineencephaiopathyGlycine cleavage (4 enzymes)Infantile seizures, lethargy, apnea, profound mental retardationAR SarcosinemiaSarcosine dehydrogenaseBenignAR Hyperoxaluria type IAlanine:glyoxylateaminotransferaseCalcium oxalate nephrolithiasis, renal failureAR Hyperoxaluria type IId-Glyceric acid dehydroge- nase/ glyoxylate reductaseCalcium oxalate nephrolithiasis, renal failureARSerinePhosphoglycerate dehydrogenase deficiencyPhosphoglycerate dehydrogenaseSeizures, microcephaly, mental retardationARProlineHyperprolinemia type IProline oxidaseBenignAR Hyperprolinemia type IIl-Pyrroline-5-carboxylate dehydrogenaseFebrile seizures, mental retardationAR HyperhydroxyprolinemiaHydroxyproline oxidaseBenignAR Prolidase deficiencyProlidaseMild mental retardation, chronic dermatitisARMethionineHypermethioninemiaMethionine adenosyltransferaseUsually benignAR S-Adenosylhomocysteine hydrolase deficiencyS-Adenosylhomocysteine hydrolaseHypotonia, mental retardation, absent tendon reflexes, delayed myelinationAR Glycine N-methyltrans- ferase deficiencyGlycine N-methyltransferaseElevated liver transaminasesARHomocystineHomocystinuriaCystathionine -synthaseLens dislocation, thrombotic vascular disease, mental retardation, osteoporosisAR Homocystinuria5,10-Methylenetetrahydro- folate reductaseMental retardation, gait and psychiatric abnormalities, recurrent strokesAR HomocystinuriaMethionine synthase (cbIE, -G)Mental retardation, hypotonia, seizures, megaloblastic anemiaAR Homocystinuria and methylmalonic acidemiaVitamin B12 lysosomal efflux and metabolism (cbIC, -D, -F)Mental retardation, lethargy, failure to thrive, hypotonia, seizures, megaloblastic anemiaARCystathionineCystathioninuriaCystathionaseBenignARCystineCystinosisCystinosin CTNS (lysosomal efflux)Renal Fanconi syndrome, rickets, photophobia, hypotonia, renal failureARS-Sulfo-I- cysteineSulfocysteinuriaSulfate oxidase or molybdenum cofactor deficiencySeizures, mental retardation, dislocated lensesARLysineHyperlysinemia, saccharopinuriaAminoadipic semialdehyde synthaseBenignAR Pyridoxine-dependent seizuresL-l-Piperideine-6-carboxylate dehydrogenaseSeizuresARLysine, tryptophanKetoadipic acidemiaKetoadipic acid dehydrogenaseBenign? Glutaric acidemia type IGlutaryl-CoA dehydrogenaseSevere dystonia and athetosis, mild mental retardationAR Glutaric acidemia type IIElectron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductaseHypoglycemia, metabolic acidosis, "sweaty feet" odor, hypotonia, cardiomyopathy, exercise-induced myopathyAROrnithineGyrate atrophy of the choroid and retinaOrnithine 5 aminotransferaseMyopia, night blindness, loss of peripheral vision, cataracts, chorioretinal degenerationARUrea cycleCarbamoylphosphate synthase-1 deficiencyCarbamoylphosphate synthase-1Lethargy progressing to coma, protein aversion, mental retardation, hyperammonemiaAR N-Acetylglutamate synthase deficiencyN-Acetylglutamate synthaseLethargy progressing to coma, protein aversion, mental retardation, hyperammonemiaAR Ornithine transcar- bamylase deficiencyOrnithine transcarbamylaseLethargy progressing to coma, protein aversion, mental retardation, hyperammonemiaXL Citrullinemia type 1Argininosuccinate synthaseLethargy progressing to coma, protein aversion, mental retardation, hyperammonemiaAR Argininosuccinic acidemiaArgininosuccinate lyaseLethargy progressing to coma, protein aversion, mental retardation, hyperammonemia, trichorrhexis nodosaAR Arginase deficiencyArginaseSpastic tetraparesis, mental retardation, mild hyperammonemiaAR Hyperornithinemia, hyperammonemia, homocitrullinuriaMitochondrial ornithine carrier ORNT1Vomiting, lethargy, failure to thrive, mental retardation, episodic confusion, hyperammonemia, protein intoleranceAR Citrullinemia type 2Mitochondrial aspartate/ glutamate carrier CTLN2Neonatal intrahepatic cholestasis, adult presentation with sudden behavioral changes and stupor, coma, hyperammonemiaARProline, ornithine, argininel-pyrroline-5-carboxylate synthase deficiencyl-pyrroline-5-carboxylate synthaseHypotonia, seizures, hyperammo- nemia, neurodegenerationARGlutamineGlutamine synthase deficiencyGlutamine synthaseBrain malformations, pachygyria, seizures, hypotonia, dysmorphic featuresARValineIsobutyryl-CoA dehydro- genase deficiencyIsobutyryl-CoA dehydrogenaseFailure to thrive, anemia, and dilated cardiomyopathy(?)ARValine, leucine, isoleucineMaple syrup urine diseaseBranched chain ketoacid dehydrogenaseLethargy, vomiting, encephalopathy, seizures, mental retardation, "maple syrup" odor, protein intoleranceARLeucineIsovaleric acidemiaIsovaleryl-CoA dehydrogenaseAcidosis, ketosis, vomiting, coma, hyperammonemia, "sweaty feet" odor, protein intoleranceAR 3-Methylcrotonyl glycinuria3-Methylcrotonyl-CoA carboxylaseStress-induced metabolic acidosis, hypotonia, hypoglycemia, "cat's urine" odorAR 3-Methyfglutaconic aciduria type 13-Methylglutaconyl-CoA hydratase deficiencyStress-induced acidosis, leukoencephalopathyAR 3-Hydroxy-3-methylglutaricaciduria3-Hydroxy-3-methylglutaryl- CoA lyaseStress-induced hypoketotic hypoglycemia and acidosis, encephalopathy, hyperammonemiaARIsoleucine2-Methylbutyryl-glycinuria2-Methylbutyryl-CoA dehydrogenaseFasting-induced metabolic acidosis/hypoglycemiaAR 2-Methyl-3-hydroxybutyryl- CoA dehydrogenase deficiency2-Methyl-3-hydroxybutyryl- CoA dehydrogenaseDevelopmental regression, seizures, and rigidity sometimes triggered by illnessesXL 3-Oxothiolase deficiency3-OxothiolaseFasting-induced acidosis and ketosis, vomiting, lethargyARValine, isoleucine, methionine, threoninePropionic academia (pccA,-B,-C)Propionyl-CoA carboxylaseMetabolic ketoacidosis, hyperammonemia, hypotonia, lethargy, coma, protein intolerance, mental retardation, hyperglycinemiaAR Multiple carboxylase/ biotinidase deficiencyHolocarboxylase synthase or biotinidaseMetabolic ketoacidosis, diffuse rash, alopecia, seizures, mental retardationAR Methylmalonic acidemia {mutase, racemase, CbIA, -B, -D)Methylmalonyl-CoA mutase/ racemase or cobalamin reductase/ adenosy (transferaseMetabolic ketoacidosis, hyperammonemia, hypertonia, lethargy, coma, protein intolerance, mental retardation, hyperglycinemia
Uronic acid
Hexose-monophosphate
Glycogen
Fructose
Carbohydrates