A full- term female infant failed to gain weight and showed metabolic acidosis in the neonatal period. A physical examination at 6 months showed failure to thrive, hypotonia, small muscle mass, severe head lag, and a persistent acidosis (p. H 7. 0 to 7. 2). Blood lactate, pyruvate, and alanine were greatly elevated. Treatment with thiamine did not alleviate the lactic acidosis. Which of the following enzymes is most likely deficient in this patient? Alanine amino transferaseb) Phosphoenolpyruvate carboxy kinasec) Pyruvate carboxylased) Pyruvate dehydrogenasee) Pyruvate kinase The right answer is- d)The symptoms are suggestive of Pyruvate dehydrogenase complex deficiency. Pyruvate dehydrogenase complex (PDC) deficiency (PDCD) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism. Pyruvate dehydrogenase, a multienzyme complex, catalyzes the conversion of pyruvate to acetyl co A. The major fate of Acetyl co A is oxidation in citric acid cycle, which is a chief metabolic cycle to derive energy from carbohydrates. Malfunction of this cycle deprives the body of energy. The impaired conversion of pyruvate to Acetyl co A leads to elevation of blood pyruvate, lactate and alanine. The persistent metabolic acidosis is due to accumulation of lactates in blood that results in nonspecific symptoms (e. Similar symptoms though mild in nature can also be observed in Thiamine deficiency, as TPP is requires as a coenzyme for PDH complex. Since in the given case the patient is resistant to supplementation with thiamine, the deficiency of thiamine is ruled out. Alanine transferase catalyzes the conversion of pyruvate to alanine (transamination). It cannot be the defect as alanine levels are also elevated. Phospho enol pyruvate carboxy kinase catalyzes the conversion of Oxaloacetate to phosphoenol pyruvate. The deficiency is rare. Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate. Pyruvate kinase catalyzes the conversion of phosphoenol pyruvate to pyruvate. The clinical manifestations in the given case are only suggestive of PDH complex deficiency. A 3- year- old female child whose growth rate has been in the lower 1. She is diagnosed as having cystic fibrosis. For which of the following vitamins is this child most likely to be at risk of deficiency? Vitamin Cb) Vitamin B6c) Folic acidd) Retinol (vitamin A)e) Riboflavin (vitamin B2)The right answer is- d) – Cystic fibrosis, is an autosomal recessive disorder affecting approximately 1 in 2. It is caused due to defective chloride ion channels of exocrine glands and epithelial tissues involving pancreas, sweat glands, and mucous glands in the respiratory, digestive, and reproductive tracts. Affected patients usually have abnormal mucus secretion resulting in recurrent respiratory infections, gastrointestinal obstruction and pancreatic enzyme dysfunction. The protein cystic fibrosis transmembrane conductance regulator (CFTR) is defective, leading to abnormal chloride transport. Because cystic fibrosis leads to pancreatic damage and diminution of the ability to secrete HCO3. Retinol is a fat soluble vitamin that must be absorbed along with lipid micelles; hence the absorption of retinol is grossly affected. A 5. 4- year- old male who was diagnosed with HIV (human immuno deficiency virus) infection 2 years back, is currently in the terminal stage. He is now cachectic and having a difficult time obtaining any caloric intake yet he refuses to take a naso gastric or gastric feeding tube. Since his muscle and organs are metabolically active, which of the following amino acids will produce both glucose and ketone bodies as an energy source? Alanineb) Tyrosinec) Prolined) Glycinee) Leucine. The right answer is b) Tyrosine. Tyrosine is the only amino acid in the given options that is both glucogenic as well as ketogenic. Upon metabolism tyrosine produce one molecule of fumarate and one molecule of acetoacetate. Fumarate is converted to Oxaloacetate (through intermediate formation of malate) which can be converted to glucose. Acetoacetate is cleaved to form 2 molecules of acetyl co A under the effect of Thiolase enzyme. Glycine is converted to serine that produces pyruvate by non oxidative deamination. Leucine is purely ketogenic. Upon metabolism it produces acetoacetate and acetyl Co. A, both are ketogenic fractions. A 4. 0 - year- old man presents with chest pain that radiates to his left jaw and shoulder. He is diagnosed with a myocardial infarct (heart attack) and is prescribed a statin medication. Statins are competitive inhibitors of HMG Co. A reductase, which converts HMG Co A to which of the following? Isopentenyl pyrophosphateb) Mevalonatec) Geranyl pyrophosphated) Farnesyl pyrophosphatee) Cholesterol. The right answer is- b) Mevalonate. The reaction catalyzed by HMG Co A reductase is the principal regulatory step in the pathway of cholesterol synthesis and is the site of action of the most effective class of cholesterol- lowering drugs, the HMG- Co. A reductase inhibitors (statins). The Path of Least Resistance: Using Data, Tools, and Technology to Improve Antimicrobial Stewardship. Bhavsar, Pharm.D., Clinical Solutions. Mevalonate is phosphorylated sequentially by ATP by three kinases, and after decarboxylation the active isoprenoid unit, Isopentenyl pyrophosphate (C5), is formed. Isopentenyl diphosphate is isomerized by a shift of the double bond to form dimethylallyl pyrophosphate, then condensed with another molecule of Isopentenyl diphosphate to form the ten- carbon intermediate Geranyl pyrophosphate (C1. A further condensation of Geranyl pyrophosphate (C1. Isopentenyl pyrophosphate forms Farnesyl pyrophosphate (C1. Cholesterol is the final product of the pathway. Which of the following compounds is the direct precursor for the heme nitrogen atoms? Glucoseb) Glycinec) Succinyl co Ad) Alaninee) Methionine. The right answer is- b) Glycine. Heme is synthesized in living cells by a pathway that requires Succinyl- Co. A, derived from the citric acid cycle in mitochondria, and the amino acid glycine. Emeritus Professor of Medicine, Physiology and Biophysics School of Medicine.The product of the condensation reaction between Succinyl- Co. A and glycine is . Through a number of further steps Heme is synthesized. Glucose does not have nitrogen in its structure to contribute towards heme formation, whereas alanine and methionine do possess amino groups but they do not contribute to Heme nitrogen. A pregnant woman is able to transfer oxygen to her fetus because fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin. Why is the affinity of fetal hemoglobin for oxygen higher? The tense form of hemoglobin is more prevalent in the circulation of the fetus. There is less 2, 3- BPG in the fetal circulation as compared to maternal circulation. Fetal hemoglobin binds 2, 3- BPG with fewer ionic bonds than the adult form. The Bohr effect is enhanced in the fetus. The oxygen- binding curve of fetal hemoglobin is shifted to the right. The right answer is - c). The enhanced uptake of maternal oxygen by fetal Hb is due to less binding of 2, 3 BPG with fetal Hb. It is not due to more prevalence of tense form of fetal hemoglobin in the circulation. It is also not due to less 2, 3 BPG in the fetal circulation, the Bohr Effect is not enhanced in the fetus and the oxygen - binding curve of fetal Hb is also not shifted to the right. In Hb A (adult Hb) when 2, 3- BPG binds to deoxyhemoglobin, it acts to stabilize the low oxygen affinity state (T state) of the oxygen carrier, exploiting the molecular symmetry and positive polarity by forming salt bridges with lysine and histidine residues in the four subunits of hemoglobin. The R state, with oxygen bound to a heme group, has a different conformation and does not allow this interaction. By selectively binding to deoxyhemoglobin, 2, 3- BPG stabilizes the T state conformation, making it harder for oxygen to bind hemoglobin and more likely to be released to adjacent tissues. Fetal hemoglobin (Hb. F) exhibits a low affinity for 2, 3- BPG, resulting in a higher binding affinity for oxygen. This increased oxygen- binding affinity relative to that of adult hemoglobin (Hb. A) is due to Hb. F’s having two . The positive histidine residues of Hb. A . That’s the way O2 flows from the mother to the fetus. A 3. 5- year- old female presents with severe dehydration and decreased urine output. Her blood urea nitrogen level is abnormally elevated because her kidneys are not able to excrete urea in the urine. In the production of urea, which of the following is an important intermediate? Serineb) Glutamatec) Prolined) Ornithinee) Leucine. The right answer is- d) Ornithine. Urea is the end product of nitrogen/amino acid metabolism. Urea formation requires the participation of 6 amino acids which are aspartic acid, ornithine, citrulline, argino succinic acid, arginine and N- Acetyl glutamate. Out of these N - Acetyl glutamate is the only amino acid that acts as an allosteric activator of Carbamoyl phosphate synthase- 1 enzyme, rest all participate in urea formation. Ornithine acts as a catalyst in the process of urea formation. Ornithine is a non standard amino acid, it is not incorporated in to tissue proteins but it participates in urea formation and polyamine synthesis. Serine does not participate in urea formation. It is glucogenic, incorporated in to tissue proteins, required for synthesis of glycine, cysteine and sphingosine. Also participates in one carbon metabolism, forming O- glycosidic linkages and is present in at the active site of many enzymes. Glutamate is a precursor of GABA, glutamine, glucogenic, a neurotransmitter and is incorporated in to tissue proteins. It does not participate in urea formation. Proline also does not participate in urea formation; it is incorporated in to tissue proteins and is present at those places where kinks or bends are needed in the folding of the proteins since it is an imino acid. Collagen is rich in hydroxy proline (its hydroxylated form). Leucine is a branched chain amino acid; it is purely ketogenic and has no role in urea formation. Which of the following is a common compound shared by the TCA cycle and the urea cycle? An error occurred while setting your user cookie. 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