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- 1.
- 2. AMINO ACID METABOLISM Anabolism(synthesis) Catabolism Functions Disorders
- 3.
- 4. Essential amino acids IPL Live Telecast in MTV I Love To Taste Leg Piece Very Much
- 5. Essential amino acids IPL Live Telecast in MTV I Love To Take LOLLY POP Very Much Glutamate Glutamine Alanine Aspartate Aspargine Tyrosine
- 6. AMINO ACID Carbon skeletonNH3 Glucose ketone bodies UREA
- 8. Acetyl coA Allaromatic aminoacids Isoleucine Leucine Lysine α ketoglutarate Glutamate Glutamine Semi essential aminoacids Proline Succinyl coA Valine Isoleucine Methionine Fumarate Phenylalanine Tyrosine OxaloAcetate Aspartate Asparagine Pyruvate Serine Alanine Cysteine Glycine Threonine Tryptophan
- 9.
- 10. AMINO ACID NH3 UREA How ammoniais formed?? Detoxification??
- 11. How NH3 isformed?? Catabolism of amino acids Purine & Pyrimidine catabolism Putrefaction
- 12. Transportation Pyruvate(muscle) alanine αKetoglutarate glutamate
- 13. SIGNIFICANCE Catabolism ofamino acids Synthesis of non essential amino acids Interconversion of aminoacids ALT – Liver diseases AST – Skeletal muscle disorders, cardiac markers & liver diseases
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- 15. Liver &kidney Urinary buffer
- 16.
- 17. MINOR PATHWAYS OF DEAMINATION L amino acid oxidase D amino acid oxidase Mono amine oxidase (MAO) Dehydratase Desulphydrase Histidase L amino acids Glycine & D amino acids Tyrosine Serine & threonine Cysteine Histidine
- 19.
- 20. SITE LIVER Partlyin mitochondria & partly in cytoplasm
- 21. PATHWAY NH3 +CO2 + NH3 2ATPs Carbamoyl phosphate CPS I
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- 23.
- 24.
- 26. ENERGETICS CPS I– 2ATPs are utilised ASS – 2ATPs are utilised TOTAL = 4 ATPs are utilised But fumarate recycle – 1NADH = 2.5ATPs are generated So net ATP utilisation is 4-2.5 = 1.5ATPs
- 27. REGULATION CPS I– rate limiting enzyme Allosteric regulation N Acetyl Glutamate NAG synthase Arginine
- 28. Protein catabolism proteinrich diet starvation DM thyroid diseases Compartmentalisation Urea cycle enzymes
- 29. UREA CYCLE DISORDERS CPS I OTC Ornithine transporter ASS ASL ARGINASE Organic acidurias & beta oxidation disorders Liver disorders Hyperammonemia type 1 Hyperammonemia type 2 HHH syndrome Citrullinemia Argininosuccinic acidemia Hyperargininemia Hepatic encephalopathy (hepatic coma)
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- 33. NH3 + CO2→ CAP + Ornithine Citrulline + Aspartic acid Argininosuccinate - Fumarate Arginine - Ornithine UREA
- 35. Clinical Significance CPSI: Hyperammonemia type I NAG synthetase deficiency OTC: Hyperammonemia type II X-linked recessive orotic aciduria
- 36. Ornithine transporter: ORNT1 Hyperammonemia Hyperornithinemia Homocitrullinuria HHHsyndrome ASS: citrullinemia high km Citrin transporter defect – Type 2
- 37. ASL: Argininosuccinic aciduria Trichorrhexisnodosa Arginase: hyperargininemia lysine-cystinuria
- 38. Ammonia toxicity DecreasedAKG Decreased glutamate Increased glutamine ATP deficient Decreased neurotransmitter (GABA) Edema of brain cells Encephalopathy Coma Respiratory alkalosis
- 39. Diagnosis: Plasmaammonia - elevated Normal – 15-45µg/dl(10-40µmol/L) Tandem MS Neonatal screening
- 40. Treatment Low proteindiet (arginine) Frequent feeds Bowel disinfection using antibiotics Lactulose Benzoate & phenylacetate CRISPR/Cas9 – gene editing
- 41. Case scenario Newbornchild with encephalopathy and respiratory alkalosis Ammonia levels were elevated Low citrulline Urine orotic acid – Normal Liver biopsy – NAG synthase Diagnosis???
- 42. GLYCINE METABOLISM Introduction: Simple Non essential Glucogenic Creatine/creatinine, glutathione, heme & nucleotide synthesis Non ketotic hyperglycinemia Glycinuria Hyperoxaluria
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- 45.
- 47. Catabolism CO2 NH3 methylene THFA Glycine Glycine synthase complex Glycinedecarboxylase Amino methyl transferase Methylene THFA synthase Lipoamide dehydrogenase PLP THFA Lipoamide NAD
- 48.
- 50. GLYCINE METABOLISM Synthesis Catabolism Functions Disorders
- 51.
- 52. SYNTHESIS CO2 NH3 methylene THFA Glycine synthase complex Serine (hydroxy methyl transferase) Threonine (Aldolase) Glyoxalate (Transaminase) Choline
- 53. CATABOLISM Glycine cleavagesystem Serine Pyruvate Gluconeogenesis Glyoxalate Oxalic acid Glycolic acid
- 54. Functions Creatine synthesis: glycine, arginine& methionine kidney / pancreas
- 56.
- 57. Glutathione : glutamate +cysteine + glycine Gamma glutamyl cysteine Glutathione Free radical scavenging – RBC membrane Detoxification Absorption of amino acids Reduction reactions
- 58. Heme synthesis: glycine+ succinyl coA Purine nucleotide synthesis C4, C5 & N7 Neurotransmitters Conjugating agent bile acids & benzoic acid
- 61. Clinical significance Nonketotic hyperglycinemia Primary hyperoxaluria type I Primary hyperoxaluria type II Glycinuria Glycine cleavage system Transaminase Glyoxalate reductase Tubular reabsorption
- 62.
- 63. Amino acid Synthesis Catabolism FunctionsDisorders Glycine GSC Serine, threonine, Glyoxalate & choline Glucogenic Serine → Pyr GCS Transamination Creatine,purine, Glutathione, heme, collagen, Neurotransmitter NKHG Hyperoxaluria Glycinuria
- 64. TYROSINE METABOLISM Introduction Anabolism Catabolism Functions Clinical significance
- 65. Introduction Aromatic Nonpolar Non essential Partly glucogenic & partly ketogenic Catecholamine, thyroxine & melanin synthesis PKU Albinism Alkaptonuria Tyrosinemia
- 66.
- 67. Catabolism Tyrosine transaminase p-hydroxy phenyl pyruvate hydroxylase Homogentisicacid oxidase Maleyl acetoacetate isomerase Fumaryl acetoacetate hydrolase Fumarate + acetoacetate (glucogenic) (ketogenic)
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- 70.
- 71. PKU Phenylalanine hydoxylase (classicalor type 1 PKU) THBP synthase or reductase deficiency
- 72. Biochemical alterations Increased phenylalanine Phenylpyruvate Phenyl acetate Phenyl lactate Mousy odour in sweat & urine Decreased tyrosine Mental retardation Delayed developmental milestones Seizures Psychosis Hypopigmentation
- 73. Diagnosis Ferric chloridetest DNPH test Guthrie test (Bacillus subtilis) Blood phenylalanine DNA study Treatment Low phenylalanine High tyrosine
- 75. Tyrosinemia Type 1– hydrolase Type 2 – transaminase (Richner-Hanhart syndrome) Type 3 – hydroxylase Neonatal – hydroxylase Hawkinsinuria
- 76. Type 1 tyrosinemia Cause: FA Hydrolase Effects: FA and succinyl acetone Hepatorenal tyrosinemia ALA dehydratase Diagnosis: succinyl acetone levels Treatment: Nitisinone
- 78. Tyrosinemia Type 1– hydrolase Type 2 – transaminase (Richner-Hanhart syndrome) Type 3 – hydroxylase Neonatal – hydroxylase Hawkinsinuria
- 79. Alkaptonuria Garrod’s tetrad Homogentisate oxidase Black colour urine Ochronosis Black urine Ferric chloride test Benedict’s test Blood/urine homogentisic acid
- 81. Albinism Tyrosinase Tyrosinase+ve type Copper deficiency Photosensitivity Photophobia and decreased vision Leucoderma Malignant melanoma Graying of hair
- 82. Parkinson’s disease Pheochromocytoma
- 83. 1. Alkaptonuria 2. Albinism 3.Hydroxymethyl transferase 4. Aldolase 5. Glyoxalate transaminase 6. Glycine decarboxylase 7. Glyoxalate reductase 8. Glyoxalate oxidase 9. Cysteine 10. Arginine a) Primary hyperoxaluria type I b) Primary hyperoxaluria type II c) Creatine d) Glutathione e) Non ketotic hyperglycinemia f) Oxalic acid g) Ochronosis h) Copper i) Serine↔glycine j) Spectrophotometric estimation k) Threonine→glycine
- 84. Tryptophan metabolism Introduction: Aromaticamino acid Non polar Essential Glucogenic & ketogenic Serotonin, melatonin & Niacin Hartnup’s disease Carcinoid tumour Pellagra
- 85. Catabolism Tryptophan tryptophan pyrrolase N Formylkyneurinine THFA Formylase Kyneurinine hydroxylase 3 OH kyneurinine kyneurinase alanine 3 OH anthranilic acid Acetoacetyl coA
- 87. Functions Serotonin Tryptophan hydroxylase THBP 5 hydroxytryptophan decarboxylase PLP 5 hydroxytryptamine (serotonin) MAO 5HIAA
- 88. 5HT receptors Mood stabiliser Regulates sleep & Appetite Temperature regulation Memory & learning Intestinal motility Coagulation & Wound healing Smooth muscle constriction vasoconstriction MAO inhibitors SSRIs TCAs
- 89. Melatonin: Serotonin acetylase Acetyl serotonin methyl transferase Melatonin Pineal gland Sleep-wake cycle Antioxidant property
- 90. Niacin Synthesis Tryptophan Fe2+ Folic acid B2 B6 3-OHanthranilic acid Quinolinic acid QPRTase Niacin mono nucleotide Desamido NAD NAD (Nicotinamide Adenine Dinucleotide)
- 91. Clinical significance Pellagra Carcinoid tumours Argentaffinoma Small intestine & appendix Excess serotonin Pellagra Urinary 5HIAA levels > 25mg/day
- 92. Hartnup’s disease: Defectivetransporter (intestine & kidney) Pellagra Urinary tryptophan Urinary indole compounds (Obermeyer’s test)
- 93. Glutamic acid Nonessential amino acid
- 94. Liver &kidney Urinary buffer
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- 99. Functions Excitatory neurotransmitter NMDAreceptor opens Ca2+ channel GABA opens cl- channel inhibitory neurotransmitter Glutathione Glutamine Arginine Proline Histidine NAG – regulates urea cycle
- 100. Clinical significance VitaminB6 deficiency Glutamic acid → GABA Seizures Alzheimer’s disease Sodium valproate
- 101. Glutamine Non essentialamino acid GLUTAMINE SYNTHETASE
- 103. Functions Trapping ofammonia in brain Urinary buffer Purine & pyrimidine synthesis Aminosugars NAD Asparagine Detoxification
- 104. Aspartic acid Nonessential Glucogenic
- 105. Functions Purine &pyrimidine synthesis Urea cycle Glycolysis Gluconeogenesis Clinical significance: dicarboxylic amino aciduria Malate aspartate shuttle
- 106. Asparagine Non essential Glucogenic Glycosylation of proteins Asparaginase - ALL Gln
- 107. Amino acid Synthesis Catabolism FunctionsDisorders Tyrosine Non Essential Phenylalanine G & K Fumarate & acetoacetate Catecholamines Melanin thyroid hormones Tyramine PKU Albinism Alkaptonuria Tyrosinemia Glutamate Non essential αKG (major) Gln, His, Arg & Proline Glucogenic αKG GABA shunt γ-carboxylation Urea cycle Neurotransmitter GABA, Glutathione Vitamin B6 deficiency & seizures Glutamine Non essential Glutamate (Glutamine synthetase) Glucogenic Glutamate (Glutaminase) Purine & pyrimidine Aminosugars, Asn, NAD Detoxification - Aspartate Non essential Oxalacetate Glucogenic Oxaloacetate Purine & Pyrimidine Urea cycle Malate-aspartate Dicarboxylic aciduria Asparagine Non essential Aspartate (Asparagine synthetase) Glucogenic Aspartate (Asparaginase) Site for Glycosylation Asparaginase – Treatment of ALL
- 108. Semi essential aminoacids
- 109. Histidine Semi Essentialamino acid Glutamate PRPP Glutamine ATP Glucogenic HISTIDINE
- 110.
- 111. Functions Buffering action Acid base catalysis Metallo proteins Hb Antioxidant property Histamine Ergothioneine Carnosine Anserine 1C pool
- 112. Mediates allergicreactions vasodilation bronchoconstriction nasal congestion Sleep wake cycle Gastric acidity
- 113. Clinical significance Histidase Histidinemia Urocanase Urocanic aciduria
- 114.
- 115. SULPHUR CONTAINING AMINO ACIDS Methionine Essential Glucogenic Transmethylation reaction Cysteine Non essential Glucogenic Glutathione, taurine, coA Homocystinuria Cystinuria Cystinosis Oasthouse syndrome
- 116. Synthesis ofcysteine/ catabolism of methionine
- 117. Homocysteine Serine Cystathionine Homoserine Cysteine trans- amination α ketohydroxy butyrate oxidative decarboxylation propionyl coA
- 118.
- 120. PAPS Sulphotransferase GAGs Sulpholipids Detoxification
- 121.
- 123. Glutathione Glutamate +cysteine + glycine
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- 126.
- 127. Coenzyme A: pantothenic acid+ cysteine
- 129. Taurine: conjugation ofbile acids Inhibitory neurotransmitter Nerve conduction & muscle contraction
- 130. Clinical significance Homocystinuria: Normal:5-15µmol/L Cystathionine synthase B6 , B12 & folic acid N5N10 methylene THFA reductase Hypothyroidism Smoking & alcohol
- 131. Increased riskof atherosclerosis interferes with collagen cross linking free radical production activation of Hageman’s factor Skeletal deformities( Marfan like features) Ectopia lentis Mental retardation Neural tube defects Blood or urine homocysteine
- 132. Amino acid Synthesis Catabolism FunctionsDisorders Methionine Essential Glucogenic Succinyl coA (Met→Hcy→Hser →propionyl coA) Transmethylation reactions (epinephrine/ choline/ melatonin/ creatine) Homocystinuria Cystinuria Cystinosis Hypermethion inemia Oasthouse syndrome Cysteine Non essential Methionine & serine Glucogenic Pyruvate PAPS Glutathione coA Taurine
- 133. Cystinuria: Defective reabsorptionof COAL Renal calculi Cyanide – nitroprusside test Plenty of fluids Alkaliniser
- 134. Cystinosis: Cystinosin Kidney– Fanconi syndrome Cornea – photophobia Liver, spleen, WBCs WBC cystine levels
- 135. Cystathioninuria –cystathionase deficiency Hypermethioninemia – MAT deficiency Oasthouse syndrome – methionine reabsorption
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- 138.
- 139. Functions Urea synthesis Polyamine Proline & Glutamate synthesis Creatine & creatinine Nitric oxide(NO . ) NOS 3 isoforms Heme FAD FMN NADPH THBP
- 140. CNS: CRH, GHRH,LHRH Endothelium: vasodilatation pulmonary HT – NO inhalation angina pectoris – nitroglycerine erectile dysfunction – sildenafil Macrophages: bactericidal Shock GIT: Intestinal motility
- 141.
- 143. DNA stabilisation Replication Transcription Translation Cell proliferation. Clinical significance: DFMO ODC Suicidal inhibition Trypnosomiasis Pneumocystis carnii
- 144. Disorders Arginine Argininase Ornithine transaminase Glutamate semi aldehyde Argininuria Gyrateatrophy of retina HHH syndrome
- 145. Proline Glutamate ATP Glutamate semialdehyde Pyrolline 5carboxylate Proline Arginine Ornithine
- 146.
- 147. Functions Collagen Siteof hydroxylation Clinical significance: Hyperprolinemia type I - Hyperprolinemia type II - Proline dehydrogenase GS dehydrogenase
- 148. Serine Hydroxy aminoacid Non essential amino acid
- 150.
- 152. Functions Site ofglycosylation Site of phosphorylation covalent modification Serine protease
- 153. Alanine synthesis serine→ pyruvate → alanine Cysteine synthesis
- 154. Selenocysteine synthesis Se+ ATP → Se-P Serine + Se-P → Selenocysteine Cotranslational modification Glutathione peroxidase Deiodinase Thioredoxin reductase
- 155. Phospholipid synthesis palmitoylcoA + serine sphingosine sphingophospholipids
- 156. 3 X methyl Serineethanolamine choline phosphatidyl ethanolamine phosphatidyl choline Phosphatidyl serine Acetyl choline
- 158. Clinical significance Azaserine glutamineanalogue inhibits purine & pyrimidine synthesis anti cancer drug Cycloserine D - alanine analogue inhibits bacterial cell wall synthesis antibiotic
- 159. Threonine Hydroxy aminoacid Essential amino acid Both glucogenic & ketogenic Threonine α keto butyrate Propionyl coA Succinyl coA Threonine Glycine + acetaldehyde
- 160.
- 162. Amino acid Synthesis Catabolism FunctionsDisorders Arginine Semi essential Glutamate Glu→GSA→Orn →Arg Glucogenic Argininase OTA Urea cycle Nitric oxide Polyamines Creatine Proline & Glu Argininuria Gyrate atrophy of retina Proline Non essential Glutamate Glu→GSA→Pro Glucogenic Proline DH GSDH Collagen - structure Hyperproline mia – Type I & II Serine Non essential 3 – PG Glycine Glucogenic Ser → pyruvate GCS Enz-action & Reg Site for glycn Gly/Ala/cys/Scys SLs/GPLs/Ach 1C pool Azaserine Cycloserine Threonine Essential G&K Threonine aldolase Site of phosphorylation & Glycosylation -
- 163. Glycine Alanine Serine Threonine Glutamate Glutamine Aspartate Aspartamine Lysine Arginine Histidine Phenylalanine Tyrosine Tryptophan Proline Leucine Isoleucine Valine Cysteine Methionine
- 164. Amino acid Synthesis Catabolism FunctionsDisorders Arginine Semi essential Glutamate Glu→GSA→Orn →Arg Glucogenic Argininase OTA Urea cycle Nitric oxide Polyamines Creatine Proline & Glu Argininuria Gyrate atrophy of retina Proline Non essential Glutamate Glu→GSA→Pro Glucogenic Proline DH GSDH Collagen - structure Hyperproline mia – Type I & II Serine Non essential 3 – PG Glycine Glucogenic Ser → pyruvate GCS Enz-action & Reg Site for glycn Gly/Ala/cys/Scys SLs/GPLs/Ach 1C pool Azaserine Cycloserine Threonine Essential G&K Threonine aldolase Site of phosphorylation & Glycosylation - Alanine Non essential Pyruvate ALT Glucogenic NH3 transport Gluconeogenesis (Glu- Ala cycle) ALT – marker for liver diseases
- 165. Lysine Basic aminoacid Essential
- 166. Catabolism Lysine + αKG Saccharopine Glutamate αAminoadipate δ semialdehyde α Aminoadipate α ketoadipate Glutaryl coA
- 167. Crotonyl coA 2 xAcetyl coA Ketogenic & glucogenic
- 168. Functions Stabilises thestructure Cross link formation (collagen) Histone Epigenetics Transaminase (PLP) Rhodopsin (11 cis retinal) Carnitine Cadaverine
- 169. Clinical significance Hyperlysinemia AASSdeficiency hyperammonemia SDH saccharopinuria Glutaric aciduria GCDH deficiency basal ganglia
- 170. Branched chain aminoacids Valine Leucine Isoleucine Essential amino acids Valine – Glucogenic Leucine – ketogenic Isoleucine – both
- 171. Glucogenic ketogenic ketogenic Glucogenic Acetyl coASuccinyl coA Acetyl coA Succinyl coA
- 172. Clinical significance Maple syrupurine disease (MSUD) Autosomal recessive Branched chain ketoacid dehydrogenase Thiamine deficiency Ketoacidosis Mental retardation Burnt sugar smell in urine Rothera’s test, DNPH Test Tandem mass spectrometry Isovaleric acidemia: Isovaleryl coA dehydrogrenase
- 174.
- 175. OBJECTIVES One carbongroups Carriers Sources Intercoversion Uses Clinical significance
- 176. ONE CARBON GROUPS Formyl (-CHO) Formimino (-CH=NH) Methenyl (-CH=) Methylene (-CH2–) Hydroxymethyl (-CH2OH) Methyl (-CH3) Carboxyl(-COO)
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- 179.
- 180.
- 181. SOURCES Formyl tryptophan Formimino histidine Hydroxy methyl choline Methylene serine glycine
- 182.
- 183. USES Transmethylation reactions Purine & pyrimidine synthesis Glycine & serine metabolism Formyl met tRNA
- 184. DISORDERS Folate deficiency Folate trap B12 deficiency Folate antagonists
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- 187.
- 188.
- 189. A 10 day old girlis being examined by her pediatrician due to concerns raised by her parents about the odd shape of her eyes. Physical examination shows no other overt abnormalities. Serum studies show a methionine concentration of 1175 μM (N <50 μM). Based upon the findings in this infant, which of the following enzymes is most likely to be deficient? ⓘ Start presenting to display the poll results on this slide.
- 190. A 2 year old boyis brought to the physician’s office for evaluation of severe developmental delay. The parents say that his urine has always had a strange musty odor. Physical examination shows the boy has fair colored hair, pale skin, and pale blue irises. Which of the following processes is most likely deficient in this patient? ⓘ Start presenting to display the poll results on this slide.
- 191. . A23 year old woman is brought to the ER because of a 1 hour history of severe pain and coldness of her left leg. History taking indicates that she dropped out of high school in the 10th grade due to difficulty with comprehension. Intelligence testing demonstrated her IQ to be 80 at that time. Her parents and two older siblings have normal intelligence and have no history of these symptoms. Physical examination shows mottling and loss of pulses in the left lower extremity and foot. Arteriography of the left lower extremity shows thrombosis of the femoral artery. This patient most likely has a metabolic disorder involving which of the following amino acids? (A) Glycine (B) Leucine (C) Methionine (D) Phenylalanine (E) Tyrosine
- 192. A physicianis examining a pediatric patient brought i n by his parents because they are disturbed by his pr ogressive mood changes and apparent heightened anxiety. Physical examination shows pellegralike skin eruptions and signs of cerebellar ataxia that include unsteady gait and uncoordinated eye movements. Serum and urinalysis show significant aminoacidemia and aciduria. Measurement of urine levels of which of the following would be most informative for a correct diagnosis? (A) Alanine (B) Alloisoleucine (C) Glutamine (D) β Hydroxybutyrate (E) Tryptophan
- 193. . A5 year old boy with severe intellectual impairment is brought to the physician because of a 4 week history of progressively frequent generalized tonic clonic seizures. There is no available record of newborn screening. He has blond hair and blue eyes. Physical examination shows patches of dry, thickened skin on his neck and inner creases of the elbows and knees. Serum studies for amino acid concentrations are pending. Urine studies show increased concentrations of phenylpyruvic and phenyllactic acids. The activity of which of the following enzymes is most likely defective in this patient? (A) Branched chain keto acid dehydrogenase (B) Dihydropteridine reductase (C) Homogentisate oxidase (D) Phenylalanine hydroxylase (E) Tyrosine aminotransferase
- 194. A 1 year oldfemale is being treating in the Emergency Department following a seizure. History indicates that the child was born at home and did not undergo screening for known congenital disorders. Blood work indicates phenylalanine concentration to be 3.7 mg/dL (N = <2 mg/dL) and tyrosine to be 0.6 mg/dL (N = 0.8 ± 0.4 mg/dL). Measurement of serum serotonin level shows it to be abnormally low. A deficiency in which of the following would most likely explain the observations in this patient? (A) Branched chain keto acid dehydrogenase (B) Dihydropteridine reductase (C) Phenylalanine hydroxylase (D) Propionyl CoA carboxylase (E) Tyrosine aminotransferase
- 195. A 3 month oldinfant is being examined in the emergency department following a seizure. Blood work indicates the child has a serum phenylalanine concentration of 650 μM (N = 30–60 μM). The attending physician places the infant on a low phenylalanine diet. Upon follow up 3 days later the level of serum phenylalanine is found to be reduced to 250 μM. However, while at home the infant developed progressive movement disorders, difficulty swallowing, seizures, and a fever. A defect in which of the following enzymes would best explain the lack of a positive outcome on the low phenylalanine diet? (A) Branched chain keto acid dehydrogenase (B) Dihydropteridine reductase (C) Phenylalanine hydroxylase (D) Tryptophan hydroxylase (E) Tyrosine hydroxylase
- 196. A 5 month oldinfant who has been experiencing lethargy, recurrent vomiting, respiratory distress, and muscular hypotonia is brought to the emergency room in a near comatose state. Lab studies show serum pH of 7.27 (N = 7.35–7.45) and bicarbonate of 12 mEq/L (N = 22–26 mEq/L). Further analysis finds elevated levels of methylmalonic acid in both serum and urine. A deficiency in which of the following enzymes would most likely allow for elimination of cobalamin deficiency as the cause of the observations in this patient? (A) Malonyl CoA decarboxylase (B) Methionine synthase (C) Methylmalonyl CoA mutase (D) Methylmalonyl CoA racemase (E) Propionyl CoA carboxylase
- 197. A 67 year oldwoman is being examined by her physician with complaints of chronic back, hip, and knee pain. Physical examination finds bluishgrey macules over the cartilaginous portions of her ears and on the sclera of her eyes. Past medical history included an aortic stenosis. The patient reported that when she sweats it seems to permanently stain her clothing. She also stated that her urine seems to get darker if she does not flush the toilet. These signs and symptoms are most likely indicative of a defect in which of the following processes? (A) Aromatic amino acid catabolism (B) Bilirubin conjugation (C) Branched chain amino acid catabolism (D) Peroxisomal fatty acid α oxidation (E) Purine nucleotide catabolism
- 198. A 1 year oldboy has recently been diagnosed with hepatocellular carcinoma following a period of progressive liver failure. Of significance to the progression of the infant’s disease was the measurement of elevated levels of tyrosine and succinylacetone in the plasma. Given these findings, which of the following disorders is most likely to be the root cause of the liver cancer in this infant? (A) Isovaleric acidemia (B) Maple syrup urine disease (C) Phenylketonuria (PKU) (D) Propionic acidemia (E) Tyrosinemia type 1
- 199.
- 200.
- 201. A 10 day oldgirl is being examined by her pediatrician due to concerns raised by her parents about the odd shape of her eyes. Physical examination shows no other overt abnormalities. Serum studies show a methionine concentration of 1175 μM (N <50 μM). Based upon the findings in this infant, which of the following enzymes is most likely to be deficient? (A) Branched chain keto acid dehydrogenase (B) Cystathionine β synthase (C) Methionine synthase (D) Phenylalanine hydroxylase (E) Tyrosine aminotransferase
- 202. A 2 year oldboy is brought to the physician’s office for evaluation of severe developmental delay. The parents say that his urine has always had a strange musty odor. Physical examination shows the boy has fair colored hair, pale skin, and pale blue irises. Which of the following processes is most likely deficient in this patient? (A) Glycine conversion to serine (B) Homocysteine conversion to cystathionine (C) Phenylalanine conversion to tyrosine (D) Tryptophan conversion to serotonin (E) Tyrosine conversion to melanin