biomedical sub test[kalplan 2001] Discussion is welcome!

zhangheng1020UID：2130513

The activity of which of the following enzymes is directly affected by citrate?
                A. Fructose-2,6-bisphosphatase
                B. Isocitrate dehydrogenase
                C. Phosphofructokinase I
                D. Pyruvate carboxylase
                E. 6-phosphogluconate dehydrogenase

zhangheng1020UID：2130513

Explanation:
        The correct answer is C. Citrate is produced by citrate synthase from acetyl CoA and oxaloacetate. This reaction takes place in the mitochondria, but citrate can move freely from the mitochondria into the cytosol. When the citric acid cycle slows down, citrate accumulates. In the cytosol, it acts as a negative allosteric regulator of phosphofructokinase I, the enzyme that catalyzes the committed step of glycolysis.
        Fructose-2,6-bisphosphatase (choice A) breaks down fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase I. Fructose-2,6-bisphosphatase is activated by cyclic AMP-dependent protein kinase.
        Isocitrate dehydrogenase (choice B) converts isocitrate to alpha-ketoglutarate in the citric acid cycle. It is allosterically stimulated by ADP and inhibited by ATP and NADH. This reaction produces NADH and CO2.
        Pyruvate carboxylase (choice D) is a mitochondrial enzyme that converts pyruvate to oxaloacetate. It is important in gluconeogenesis and replenishes the oxaloacetate in the citric acid cycle.
        6-phosphogluconate dehydrogenase (choice E) converts 6-phosphogluconate to ribulose 5-phosphate in the pentose phosphate shunt pathway.

zhangheng1020UID：2130513

Which of the following enzymes is stimulated by glucagon?
                A. Acetyl-CoA carboxylase
                B. Glycogen phosphorylase
                C. Glycogen synthase
                D. HMG-CoA reductase
                E. Pyruvate kinase

zhangheng1020UID：2130513

Explanation:
         The correct answer is B. Before you started analyzing all of the answer choices you should have reminded yourself that glucagon increases serum glucose. So an enzyme stimulated by glucagon might be involved in either the breakdown of glycogen to glucose (glycogenolysis) or in the creation of glucose from noncarbohydrate precursors (gluconeogenesis). Glycogen phosphorylase catalyzes the first step in glycogenolysis; it makes sense that it would be stimulated by glucagon.
         Acetyl-CoA carboxylase (choice A) catalyzes the first step in fatty acid synthesis, an anabolic process that would be stimulated by insulin, not glucagon.
         As its name implies, glycogen synthase (choice C) is involved in the synthesis of glycogen. Glucagon (and  epinephrine) stimulate the phosphorylation and inactivation of glycogen synthase.
         HMG-CoA reductase (choice D) is the key enzyme involved in the synthesis of cholesterol. Since this is an anabolic process that occurs in the well-fed state, you would expect it to be stimulated by insulin and inhibited by glucagon (which it is).
         Pyruvate kinase (choice E) catalyzes the last reaction of glycolysis. You would expect it to be inhibited by glucagon (thus decreasing the amount of glucose consumption). Glucagon promotes the phosphorylation of pyruvate kinase, which renders it inactive.

zhangheng1020UID：2130513

Which of the following inhibits the activity of acetyl-CoA carboxylase?
                A. Citrate
                B. Glucagon
                C. High-carbohydrate, low-fat diet
                D. Insulin

zhangheng1020UID：2130513

Explanation:
         The correct answer is B. The key thing to remember here is that acetyl-CoA carboxylase catalyzes the first and rate-limiting step of fatty acid synthesis. If you got that far, you could have figured out which of the choices would inhibit the synthesis of fatty acids. Certainly glucagon, a catabolic hormone released in response to low blood glucose, would be a likely candidate to inhibit the synthesis of fatty acids. In fact, glucagon inhibits fatty acid synthesis by a cAMP-dependent phosphorylation of acetyl-CoA carboxylase. Conversely, glucagons stimulates fatty acid oxidation.
         Citrate (choice A) is a key player in fatty acid synthesis (citrate shuttle). Therefore, the presence of citrate would stimulate, not inhibit, acetyl-CoA carboxylase.
         A high-carbohydrate, low-fat diet (choice C) would stimulate, not inhibit, the synthesis of fatty acids.
         In contrast to glucagon, insulin (choice D) is an anabolic hormone that promotes fatty acid synthesis and therefore would stimulate acetyl-CoA carboxylase. It does so by dephosphorylating the enzyme.

zhangheng1020UID：2130513

An individual lacking the enzyme tyrosinase would be particularly predisposed to develop which of the following?
                A. Glioblastoma multiforme
                B. Hemangioblastoma
                C. Hepatoma
                D. Melanoma
                E. Renal cell carcinoma

zhangheng1020UID：2130513

Explanation:
         The correct answer is D. This question is simple if you know that tyrosinase is an enzyme in the biosynthetic pathway for melanin formation from tyrosine. A lack of tyrosinase causes one form of albinism; a second form is caused by defective tyrosine uptake. Patients with albinism are vulnerable to developing cancers of the skin of all types, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The melanomas are unusual in that they are non-pigmented (amelanotic) rather than black, since the patients cannot form melanin.

樱桃小丸子/丸丸UID：2160265

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zhangheng1020UID：2130513

44
A newborn baby has multiple hemorrhages. Clotting studies demonstrate an elevated prothrombin time. An abnormality of which of the following biochemical processes is likely present in this patient?
                A. Conversion of homocysteine to methionine
                B. Conversion of methylmalonyl CoA to succinyl CoA
                C. Degradation of cystathionine
                D. Formation of gamma-carboxyglutamate residues
                E. Hydroxylation of proline

zhangheng1020UID：2130513

Explanation:
        The correct answer is D. Deficiency of vitamin K produces a clotting disorder characterized by an elevated prothrombin time and easy bleeding, particularly in neonates (hemorrhagic disease of the newborn). The biochemical basis for this hemorrhagic tendency is that glutamate residues on Factors II (Thrombin), VII, IX, and X must be converted to gamma-carboxyglutamate residues (in a vitamin K-requiring reaction) for optimal activity.
        The conversion of homocysteine to methionine (choice A) requires vitamin B12.
        Conversion of methylmalonyl CoA to succinyl CoA (choice B) requires vitamin B12.
        Degradation of cystathionine (choice C) requires vitamin B6.
        Hydroxylation of proline (choice E) requires vitamin C. Vitamin C deficiency can cause easy bruising, but will not prolong the prothrombin time.

zhangheng1020UID：2130513

A very ill infant is admitted to the hospital. Laboratory examination reveals a very high serum concentration of lactic acid. In addition to taking steps to correct the acidosis, the attending physician prescribes thiamine. The  rationale for thiamine administration is that thiamine is converted to a coenzyme used by which of the following enzymes?
                A. Lactate dehydrogenase
                B. Pyruvate carboxylase
                C. Pyruvate dehydrogenase
                D. Pyruvate kinase
                E. Transketolase

zhangheng1020UID：2130513

Explanation:
         The correct answer is C. Thiamine is a water-soluble vitamin that is converted to the coenzyme thiamine pyrophosphate. This coenzyme is used by pyruvate dehydrogenase to convert pyruvate to acetyl coenzyme A. In the absence of thiamine, pyruvate accumulates and can be converted by lactate dehydrogenase to lactate, which is spilled in the blood causing lactic acidosis.
         Lactate dehydrogenase (choice A) produces lactate from pyruvate but does not use thiamine pyrophosphate. Some lactic acidosis might be produced by decreased pyruvate carboxylase activity (choice B), but the enzyme requires biotin rather than thiamine pyrophosphate. Pyruvate kinase (choice D) makes pyruvate from phosphoenolpyruvate, but does not use thiamine pyrophosphate.  Transketolase (choice E) requires thiamine pyrophosphate, but operates in another pathway (pentose phosphate pathway). Decreased transketolase activity is not associated with the development of lactic acidosis.

zhangheng1020UID：2130513

A 69-year-old edentulous alcoholic male who lives alone is admitted to the hospital for evaluation of a shoulder wound that is not healing well. On physical examination, numerous ecchymoses are noted on the posterior aspect of his legs and thighs. Careful examination of the man's skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds. Laboratory examination is remarkable for a hemoglobin of 10 (normal 14-18 g/dL); no other hematologic abnormalities are noted. Therapy should consist of
                 A. administration of factor VIII
                 B. administration of iron
                 C. administration of vitamin B12
                 D. administration of vitamin C
                 E. administration of vitamin K

zhangheng1020UID：2130513

Explanation:
         The correct answer is D. The patient described suffers from scurvy, due to a deficiency of dietary vitamin C. Absence of vitamin C leads to impaired hydroxylation of proline residues in the nascent procollagen chains,  leading to weakness of blood vessel walls. Clinically, the deficiency syndrome is characterized by perifollicular hemorrhages, fragmentation of hairs, purpura, ecchymoses, splinter hemorrhages, and hemorrhages into muscle. In patients with normal dentition, gum changes (swelling, bleeding, loosening of teeth) are also noted. Without supplementation with vitamin C, death may eventually occur.
         Administration of factor VIII (choice A) would be indicated for factor VIII deficiency, which would also lead to a prolonged PTT (partial thromboplastin time), which was not noted.
         Administration of iron (choice B) would be of benefit in iron-deficiency anemia, but there is no indication of a  hypochromic, microcytic anemia in this patient. The anemia of scurvy is typically normochromic and normocytic, due to bleeding.
         Administration of vitamin B12(choice C) would be indicated for a megaloblastic anemia. Although a macrocytic anemia may be observed in scurvy (due to concomitant dietary folate deficiency or perturbations in the folate pool), this patient did not show macrocytosis.
         Administration of vitamin K (choice E) would be appropriate in the setting of vitamin K deficiency, which would produce prolongations of the prothrombin time (PT), followed eventually by prolongation of the PTT as the vitamin K-dependent factors (II, VII, IX, X, protein C, and protein S) are depleted.