biomedical sub test[kalplan 2001] Discussion is welcome!

zhangheng1020UID：2130513

A 24-year-old graduate student presents to a physician with complaints of severe muscle cramps and weakness with even mild exercise. Muscle biopsy demonstrates glycogen accumulation, but hepatic biopsy is unremarkable. Which of the following is the most likely diagnosis?
                 A. Hartnup's disease
                 B. Krabbe's disease
                 C. McArdle's disease
                 D. Niemann-Pick disease
                 E. Von Gierke's disease

zhangheng1020UID：2130513

Explanation:
         The correct answer is C. A variety of glycogen storage diseases exist, corresponding to defects in different enzymes in glycogen metabolism; most of these involve the liver. McArdle's disease (Type V glycogen storage disease), due to a defect in muscle phosphorylase, is restricted to skeletal muscle. The presentation described in the question stem is typical. Many affected individuals also experience myoglobinuria. Definitive diagnosis is based on demonstration of myophosphorylase deficiency.
         Hartnup's disease (choice A) is a disorder of amino acid transport.
         Krabbe's disease (choice B) is a lysosomal storage disease.
         Niemann-Pick disease (choice D) is a lysosomal storage disease.
         Von Gierke's disease (choice E) is a glycogen storage disease with prominent involvement of liver, intestine, and kidney.

zhangheng1020UID：2130513

Which of the following metabolic processes occurs exclusively in the mitochondria?
                A. Cholesterol synthesis
               B. Fatty acid synthesis
                C. Gluconeogenesis
                D. Glycolysis
                E. Hexose monophosphate shunt
                F. Ketone body synthesis
                G. Urea cycle

zhangheng1020UID：2130513

Explanation:
         The correct answer is F. Of the processes listed, only ketone body synthesis occurs exclusively in the mitochondria. Other mitochondrial processes include the production of acetyl-CoA, the TCA cycle, the electron  transport chain, and fatty acid oxidation.
         Processes that occur exclusively in the cytoplasm include cholesterol synthesis (choice A; in cytosol or in ER),  fatty acid synthesis (choice B), glycolysis (choice D), and the hexose monophosphate shunt (choice E).
         Note that gluconeogenesis (choice C) and the urea cycle (choice G) occur in both the mitochondria and the cytoplasm.

zhangheng1020UID：2130513

A physician from the United States decides to take a sabbatical from his responsibilities at a teaching hospital to work in a clinic in a remote part of Africa. During his first week at the clinic, he is told that he will be seeing a patient with glucose-6-phosphate dehydrogenase deficiency. Which of the following will be the most likely clinical  presentation of this patient?
                A. A 6-month-old child who develops severe anemia following a respiratory tract infection
                B. A child who develops hemoglobinuria following a meal of beans
                C. A neonate with an enlarged spleen and severe anemia
                D. An adult who develops anemia following use of antimalarial drugs
                E. An adult who develops severe shortness of breath during an airplane ride

zhangheng1020UID：2130513

Explanation:
         The correct answer is B. In Africa, the classic presentation of glucose-6-phosphate dehydrogenase deficiency is a child who eats a meal of beans (Vicia fava) and several hours later develops hemoglobinuria and peripheral vascular collapse secondary to intravascular hemolysis as a result of the oxidant injury initiated by the fava beans. Blood studies in this setting show a rapid fall in total hemoglobin and a rise in free plasma hemoglobin, accompanied by a rise in unconjugated bilirubin and a fall in haptoglobin. The episode usually resolves spontaneously several days later. Today, the classic presentation is less common in developed countries than is a slower onset syndrome beginning 1-3 days after starting an antimalarial drug, sulfonamide, or other antioxidant drug. Rarely, glucose-6-phosphate dehydrogenase deficiency presents as neonatal jaundice or with chronic hemolysis.

zhangheng1020UID：2130513

A patient with familial hypercholesterolemia undergoes a detailed serum lipid and lipoprotein analysis. Studies demonstrate elevated cholesterol in the form of increased LDL without elevation of other lipids. This patient's hyperlipidemia is best classified as which of the following types?
                A. Type 1
                B. Type 2a
                C. Type 2b
                D. Type 3
                E. Type 5

zhangheng1020UID：2130513

Explanation:
         The correct answer is B. Hyperlipidemia has been subclassified based on the lipid and lipoprotein profiles. Type 2a, which this patient has, can be seen in a hereditary form, known as familial hypercholesterolemia, and also in secondary, acquired forms related to nephritic syndrome and hyperthyroidism. The root problem appears to be   a deficiency of LDL receptors, which leads to a specific elevation of cholesterol in the form of increased LDL  Heterozygotes for the hereditary form generally develop cardiovascular disease from 30 to 50 years of age.  Homozygotes may have cardiovascular disease in childhood.
         Type 1 (choice A) is characterized by isolated elevation of chylomicrons.
         Type 2b (choice C) is characterized by elevations of both cholesterol and triglycerides in the form of LDL and  VLDL.
         Type 3 (choice D) is characterized by elevations of triglycerides and cholesterol in the form of chylomicron remnants and IDL.
         Type 5 (choice E) is characterized by elevations of triglycerides and cholesterol in the form of VLDL and chylomicrons.

[ Last edited by zhangheng1020 on 2005-12-1 at 09:40 ]

zhangheng1020UID：2130513

During the isolation of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) from post-mortem human brain tissue, researchers find that the peptide is rapidly degraded by peptidases in 1 minute at 37 C. Detailed analysis of the peptide cleavage pattern of Met-enkephalin is investigated with two candidate enzymes. Using the drug bestatin, the investigators found no detectable Tyr-Gly-Gly-Phe-Met but did find significant concentrations of Tyr-Gly-Gly. Using thiorphan, there was no detectable Tyr-Gly-Gly-Phe-Met, but there was a high concentration of Tyr. Which of the following is the best conclusion about Met-enkephalin metabolism that can be drawn from these data?
             A. Bestatin inhibits an aminopeptidase, and thiorphan inhibits an endopeptidase in the degradative pathway
             B. Bestatin inhibits a carboxypeptidase in the degradative pathway
             C. Bestatin inhibits an endopeptidase in the degradative pathway
             D. Thiorphan inhibits an aminopeptidase, and bestatin inhibits an endopeptidase in the degradative pathway
             E. Thiorphan inhibits an aminopeptidase in the degradative pathway

zhangheng1020UID：2130513

Explanation:
      The correct answer is A. Met-enkephalin, the most abundant opioid peptide in the human brain, undergoes two routes of metabolism. One route releases a tripeptide and therefore is the result of a peptidase that cuts an amino acid bond within the molecule: an endopeptidase. The other route releases free tyrosine and therefore is an exopeptidase. Exopeptidases can remove amino acid residues from the amino- or carboxyl-terminus of the protein. By convention, all peptide sequences are given from the N to the C terminus, the direction of translation. Tyrosine is therefore at the amino-terminus of Met-enkephalin, and its release is the result of digestion by an aminopeptidase.
      The scientists have used two drugs to highlight the two enzymatic pathways. With bestatin, Met-enkephalin is metabolized only to the tripeptide; therefore bestatin inhibits the aminopeptidase enzyme, preventing release of free tyrosine residues. With thiorphan, Met-enkephalin is metabolized to free tyrosine; the tripeptide is no longer formed. Thiorphan is an inhibitor of the endopeptidase. The lack of persistence of Met-enkephalin in the presence of an enzyme inhibitor is evidence that the peptide's metabolism is shifted in the direction of the noninhibited enzyme. A schematic of the metabolism would be:
     Tyrosine cannot be the result of carboxypeptidase activity (choice B), since the carboxyl-terminus of Met-enkephalin is a methionine.
      Bestatin inhibits an aminopeptidase, not an endopeptidase (choice C). An endopeptidase would not release a free amino acid residue.
      Met-enkephalin is indeed metabolized by an aminopeptidase and an endopeptidase, but bestatin inhibits the  aminopeptidase and thiorphan inhibits the endopeptidase (compare with choice D).
      Thiorphan does not inhibit an aminopeptidase (choice E); furthermore, such an enzyme would release a free Tyr and a tetrapeptide.

zhangheng1020UID：2130513

The parents of a 6-month-old child who was normal at birth bring her into the clinic. Since their emigration to the   U.S. from Eastern Europe soon after her birth, the child has developed diminished responsiveness, progressive blindness and deafness, and recently, seizures. Serum levels of which of the following compounds would be expected to be decreased in both of the parents?
                A. Dystrophin
                B. Hexosaminidase A
                C. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
                D. Phenylalanine hydroxylase
                E. Vitamin D3

zhangheng1020UID：2130513

Explanation:
        The correct answer is B. This patient has Tay-Sachs disease, an autosomal recessive disorder caused by the  deficiency of hexosaminidase A, which leads to the accumulation of ganglioside GM2 in neurons, producing a  degenerative neurologic disease. Children appear normal at birth, but then begin to suffer from diminished  responsiveness, deafness, blindness, loss of neurologic function, and seizures. A cherry-red spot on the macula may be seen by ophthalmoscopic examination. Death usually occurs by 4 to 5 years of age. There is no therapy. The incidence is higher among Jews of Eastern European descent. Since the parents must be heterozygotes for the mutant hexosaminidase A allele, they would be expected to have diminished levels of the enzyme.
        A defect in the dystrophin (choice A) gene produces Duchenne muscular dystrophy, characterized by onset of  weakness in early childhood.
        A severe deficiency in HGPRT (choice C) will lead to Lesch-Nyhan syndrome, characterized by excessive uric acid production, mental retardation, spasticity, self-mutilation, and aggressive, destructive behavior.
        Deficiency of phenylalanine hydroxylase (choice D) results in classic phenylketonuria, a disease in which  phenylalanine, phenylpyruvate, phenylacetate, and phenyllactate accumulate in plasma and urine. Clinically, there is a musty body odor and mental retardation.
        Hypophosphatemic rickets is an X-linked dominant condition causing abnormal regulation of vitamin D3 (choice E) metabolism and defects in renal tubular phosphate transport. Symptoms include growth retardation, osteomalacia, and rickets.

zhangheng1020UID：2130513

Poor oxygenation of tissues decreases the production of ATP necessary for many cellular functions. Which of the  following processes is most immediately compromised in a typical cell when ATP production is inadequate?
                 A. Complex carbohydrate synthesis
                 B. Lipid synthesis
                 C. Na+/K+ ATPase function
                 D. Nucleic acid synthesis
                 E. Protein synthesis

zhangheng1020UID：2130513

Explanation:
         The correct answer is C. While ATP is important in cellular synthetic functions, its role in maintaining the Na+/ K+ exchange across the plasmalemma is actually the most immediately important function for most cells. The direct effect of this is the energy (ATP) driven exchange of 3 Na+ ions (which go from inside the cell to outside) for 2 K+ ions (which go from outside to inside). This process requires considerable energy (1 ATP per 3Na+/2K+ exchange), since both the Na+ and K+ are traveling against a concentration gradient. This direct effect of the Na+/ K+ ATPase may seem trivial, but the secondary consequences are dramatic. The Na+/ K+  ATPase helps establish the transmembrane potential of the cell (because the quantitatively uneven exchange of Na+/ K+ drives more positive ions out of the cell than in) and also both the Na+ and K+ gradients. All of these facilitate a wide variety of exchanges and transmembrane transport systems that allow entry into the cell of the large variety of small molecules and ions that it needs. The first microscopically visibl effect of significant hypoxia is cellular edema, which is a consequence of distorted water balance, also an indirect function of the Na+/ K+ ATPase.

zhangheng1020UID：2130513

Urine screening of an apparently healthy pregnant woman demonstrates a positive Clinitest reaction. However, blood glucose levels were within normal limits, and more specific testing for urine glucose is negative. The woman has been unaware of any metabolic problems and has been living a normal life. Deficiency of which of thefollowing enzymes would most likely produce this presentation?
                 A. Fructokinase
                 B. Fructose 1-phosphate aldolase
                 C. Galactose 1-P-uridyl transferase
                 D. Lactase
                 E. Pyruvate dehydrogenase