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NST103 Final, 5/18/06 Spring 2006 (200 points Total) Name SID I. (4 pts each = 48 pts) Choose a single best answer: 1.Which of the following processes require energy? a. Transfer of glucose molecules across a cell membrane using the GLUT family of transporters b. Transfer of glucose across the brush border membrane of enterocytes c. Transfer of cholesterol across the brush border membrane of enterocytes d. Transfer of the amino group from an amino acid to a ketoacid via a transaminase e. Transfer of fatty acids across the mitochondrial membrane Answer ____B___________ 2.Which of the following molecules can be transported from the lumen into enterocyte without further digestion? a. Retinyl esters b. Disaccharides c. Diacylglycerides d. Cholesterol esters e. Dipeptides Answer ____E___________ 3.Dietary fat soluble vitamins are delivered first to which of the following organs/tissues? a. Adipose tissue b. Adipose tissue capillaries c. Chylomicron remnants d. Liver e. Muscle Answer ____D__________ 4.Which molecules directly contribute the nitrogen that is incorporated into the urea molecule? a. Glutamine and alanine b. Glutamine and aspartate c. Ammonia and aspartate d. Ornithine and ammonia e. Citrulline and glutamate Answer ____C___________ 5.Which hormone influences energy expenditure by increasing resting metabolic rate? a. Thyroid hormone b. Glucocorticoids c. Insulin d. Catecholamines e. Epinephrine Answer _____A__________ 6.Vitamin B12 is required for metabolism of some amino acids because? a. It is a coenzyme for aminotransferase enzymes b. It facilitates intramolecular transfer of alkyl groups and hydrogen atoms c. It increases transcription of key enzymes d. Transcobalamin facilitates transfer of amino groups e. It serves as a coenzyme for methionine synthase Answer ____B___________ 1 of 7 7.In the U.S. some foods are fortified with folate because folate deficiency is associated with? a. Increased risk of cancer b. Homocysteine accumulation c. An associated deficiency in Vitamin B12 d. Inadequate DNA methylation e. Neural tube defects Answer _____E__________ 8.To have Vitamin A activity, a molecule must be able to be metabolized to which product? a. Retinol. b. Retinal. c. Retinoic acid d. Retinyl ester e. Retinoid Answer _____C__________ 9.Vitamin K deficiency results in abnormal blood clotting because a. Platelets do not aggregate due to insufficient glycoprotein b. Calcification of the soft tissue at the wound site is not adequate c. Prothrombin is not adequately activated d. The activity of matrix gla protein is reduced e. Transcription of the fibrinogen gene is inhibited Answer _____C__________ 10. Which statement regarding hemoglobin degradation is true? a. Hemoglobin degradation rate is dependent on turnover rate of erythrocytes b. The globin portion of the molecule is released and can condense with a newly synthesized heme molecule c. Heme degradation is regulated via aminolevulinate synthase d. The released iron molecule is transferred to the ferrochelatase enzyme e. Pyridoxal phosphate serves as coenzyme for heme oxygenase Answer _____B__________ 11. Which is true about vitamin C? a. Vitamin C can be synthesized from glucose in all mammals. b. Vitamin C cannot be synthesized from glucose in humans c. Vitamin C cannot be synthesized from dehydroascorbate in humans d. Vitamin C cannot be converted to dehydroascorbic acid in humans e. Vitamin C cannot be regenerated from the ascorbate free radical in humans Answer _____B__________ 12. Which is true about bone turnover? a. Osteoblasts secrete acid to degrade bone and provide Ca for the body b. Osteoclasts synthesize bone matrix proteins c. Vitamin D stimulates bone growth regardless of plasma calcium level d. Blood vessels develop as new bone is formed e. Parathyroid hormone stimulates synthesis of new bone Answer _____D__________ 2 of 7 II. (1pt each = 35 pts) Fill in the blanks: 1. Vitamin C is required for hydroxylation of the amino acids Proline and ___Lysine____________, facilitating coiling of the protein _______(tropo)Collagen________ . 2. IF Intrinsic factor is a binding protein required for receptor-mediated transport of vitamin B12 across the gut epithelium. TC-II transcobalamin Is a binding protein required for transport of vitamin B12 into tissues. 3. Mobilferrin or DMT1 is a protein that transports iron across the brush border of epithelial cells. Transferrin is a binding protein required for transport of iron from one tissue to another. Ferritin is a binding protein that facilitates intracellular storage of iron. 4. Retinoic acid and 1,25-dihydroxy Vitamin D both influence binding to Receptors in the Nucleus Transcription of cells. by 5. During fasting, two hormones that are likely to be elevated are Glucorcorticoids and Glucagon . A hormone that is likely to be reduced is ____Insulin__________. 6. HDL retrieves cholesterol from peripheral tissue via the interaction between the apoprotein, ___Apo A-1_____ and the ABC receptor. In HDL particles, the enzyme LCAT converts the cholesterol into Cholesterol ester , which is transferred into LDL particles using the enzyme CETP . The process by which cholesterol is transported from peripheral tissues to the liver is referred to as reverse cholesterol transport. 7. -oxidation requires mobilization of TAG stores via the enzyme HSL , transport of fatty acids to tissues, entry into mitochondria via the transporter __CPT1, CAT, CPTII_., and hydrolysis resulting in production of AcCoA (name molecule). 8. During a prolonged fast, muscle is the tissue that provides most of the substrate that is used for gluconeogenesis. Two metabolic pathways required for this to occur include the urea cycle and the TCA cycle . 9. During a prolonged fast, Adipose is the tissue that provides most of the substrate that is used to produce the ketone bodies that are synthesized primarily within the Mitochondria (name cellular compartment) of cells in the Liver (name the organ). These ketone bodies are used by other tissues for Energy . 10. AcetylCoA Carboxylase requires the coenzyme _Biotin__ and catalyzes the flux generating step for the synthesis of ____FFA______. 11. Essential fatty acids such as ____Linoleic, Linolenic_____ are required in the diet because humans do not have the appropriate enzymes generally called _____Desaturases___ to create certain double bonds. 12. The reducing equivalent, ___NADH___ ,is needed in the cytosol for gluconeogenesis. Glycolysis requires the reducing equivalent,___NAD+___, in the cytosol. 3 of 7 III. (4pts each =24pts) State whether the following statements are true or false, provide a justification for your answer: 1. Dietary fat promotes absorption of vitamin E. TRUE. Lumenal fat promotes formation of micells, allowing Vit E incorporated into micelles since they are fat soluble 2. There are health consequences of both low and high concentrations of plasma calcium. TRUE. Too low, hypocalcemia; too high, hypercalcification of soft tissues 3. Acetyl CoA is a substrate for gluconeogenesis in the fasting state FALSE. Use of Ac CoA for this purpose leads to depletion of TCA intermediates 4. Orange juice may increase efficiency of iron absorption. TRUE. C reduces Fe3+ to Fe2+ increasing solubility and absorption 5. Levels of the hormone form of Vitamin D (1,25-dihydroxy D) are to some extent self-regulated. TRUE - Inhibits formation by inhibiting 1-OHase in kidney. Increases excretion by activating 24-OHase leading to (1,)24,25OH Dexcreted 6. It is advantageous to have glucose transporters in the liver that have a high Km. TRUE. With a high Km, glucose is not extracted by the liver when glucose concentrations are low, sparing glucose for use by other tissues. Only at high concentrations, would liver effectively extract glucose from plasma and metabolize it. Thus, a high Km glut is preferred in the liver as that helps coordinate needs of various organs. 4 of 7 IV. (1pt each =13 pts) Indicate the name of the vitamin associated with each of the following statements. (You can use one vitamin more than once) Prevents osteomalacia Cures acute cystic acne Deficiency causes megaloblastic anemia Deficiency causes microcytic anemia Deficiency causes dementia, dermatitis and diarrhea Required for post-translational modification of osteocalcin A fat-soluble vitamin that has no known means of storage in liver Deficiency causes beriberi May cause birth defects if taken in excess Reverses xerophthalmia Is reversibly dephosphorylated for transport across cell membranes A fat-soluble vitamin that acts as an antioxidant A water-soluble vitamin that acts as an antioxidant ____1,25 (OH)2 D_________ _____A ________________ _______Folate, B12_______ (accept Fe, Cu, Zn) B6_____ _____Niacin_____________ ______Vit K______ _________K______________ _____Thiamin_________ ______A___________ _____A_______ ______thiamin______ ____ Vit E________ ________Vit C___________ V. (1pt each = 6 pts) Indicate the name of the mineral associated with each of the following statements. (You can use one mineral more than once). Forms a complex with ATP to neutralize its positive (should be negative)charge Mg__________ Is involved in electron transport via cytochromes ________Fe_____________ Is a component of Vitamin B12 ________Co______________ Is a second messenger ________Ca______________ Required for post-translational modification of some proteins ________P______________ Required for uptake of Vitamin B12 into enterocytes ________Ca____________ V. (1pt each = 14 pts) Fill in the blanks with the appropriate term. Type of reaction used to convert glutamate to ammonia and -ketoglutarate____Deamination_____ Type of reaction used to convert glutamine to ammonia plus glutamate _______Deamidation____ Absorption process that requires a protein transporter by not energy ____Facilitated Diffusion_ Absorption process that allows simultaneous absorption of numerous molecules _______Endocytosis_______ A characteristic of food that regulates emptying of the stomach ____Energy Content_____ An enzyme required for digestion of dietary lipid Gastric Lipase (& others A key absorption process used to transport amino acids across enterocyte membranes Facilitated, 2ndary active The term used to describe reabsorption of bile acids from the intestine Enterohepatic recirculation A characteristic of food that regulates emptying of the stomach _____BLANK____ A structure that forces nutrients to be transported across (rather than between) enterocytes Tight junctions (terminal web) The type of compound formed when an amino group interacts with a reducing sugar and produces a double bond between the nitrogen and carbon atoms _____Schiff base________ An enzyme required for digestion of dietary lipid _______BLANK _______ The type of cell in the pancreas that produces digestive enzymes _______Acinar_______ The type of cell in the stomach in which histamine is formed _______ECL cells______ 5 of 7 VI. Answer the questions briefly: (6 pts ea = 60 pts) 1. Describe how the health of the eye progressively deteriorates with increasingly more severe Vitamin A deficiency. Explain what accounts for this progression. Vit A deficiency leads to night blindness (1) due to lack of retinal for production of rhodopsin (2) . More severe deficiency leads to disruption of protective epithelial layers (1) due to lack of RA as transcription factor for synthesis of key proteins (2). This has more serious effects that are eventually not reversible. 2. Describe the importance of “by pass” steps in glycolysis and gluconeogenesis. By pass steps allow differential regulation of glycolysis and GNG. Since different enzymes serve to catalyze the forward and reverse directions at these steps, 3. Describe the relevance of the pentose phosphate pathway to the synthesis of triacylglycerides in the liver. Produces NADPH needed to synthesize FA, NADPH required for reduction steps of DNL. FFA used to synthesize TAG. 4. Explain why HMG-CoA reductase inhibitors, commercially known as statins, are expected to be very effective plasma cholesterol-lowering drugs. Cholesterol is contributed to plasma from two sources – diet and newly synthesized in body (de novo cholesterolgenesis) HMG-CoA reductase is rate limiting step in de novo chol synth. Limiting new synthesis may reduce cholesterol levels in plasma. 5. Explain the theoretical rationale for recommending that persons at high risk of type 2 diabetes consume foods and meals that have a low glycemic index response. When low glycemic index foods are consumed, there should be more moderate postprandial increases in plasma levels of glucose and insulin. This suggests that plasma glucose levels can be maintained will need for less insulin, which reduces requirement for pancreas to produce insulin. This reduces stress to pancreas. Also, lower insulin levels guard against development of insulin resistance in tissues. 6 of 7 6. Explain how the process of de novo lipogenesis suppresses β-oxidation. MalonylCoA, an important intermediate in the DNL pathway, inhibits CPT1 in mitochondria. This transporter is needed to move activated fatty acids from the cytosol into the mitochondria where they would be b-oxidized to produce acetyl CoA. Thus, the production of malonyl CoA that accompanies DNL inhibits the transport protein needed to deliver substrate to the mitochondria for b-oxidation. 7. Explain what is meant by secondary active transport. Provide an example of a nutrient that can be transported by this process. Energy required for one process, the result of which allows a second process to occur without direct input of energy. Eg. E used to transport Na at basolateral membrane out of cell against conc gradient, maintaining low intracellular [Na]. The concentration gradient between the high luminal [Na] and low intracellular [Na] drives intake of Glucose since Na & Glucose are co-transported. 8. Briefly describe the process by which lipid, newly synthesized by the liver, would be delivered to peripheral tissues. Be sure to mention the key particle(s), apoprotein(s) and receptor(s) that would be involved. Lipid incorporated into VLDL with Apo C-II, E, B-100, to capillaries of muscle and AT. VLDL are recognized by LPL via C-II. LPL in tissue facilitates lipolysis of TAG in VLDL, and released FFA can be absorbed by muscle and AT. IDL particles remain and can return to the circulation. Like VLDL, IDL can be recognized by LPL, and further lipolysis produces LDL particles, which also can be released into the plasma. Since Apo E & B-100 are ligands for the LDL-Receptor in liver and other tissues, these particles can be endocytosed into liver and degraded. 9. Describe two advantages to the body of having components of the urea cycle in several tissues/organs. Use at least one specific example to illustrate each advantage. The metabolic processes occurring in one organ can complement the other, serving the whole body. Eg. Intestine can process much of the glutamine delivered from muscle; Intermediates can be exported and used for other processes without compromising the overall cycle. Eg. Production of ornithine and citrulline by intestine and exportation to liver & kidney. Production of arginine by kidney with exportation to muscle & other tissues for protein synthesis. Toxicity is guarded against. Eg. Large amount of ammonia produced by intestine is delivered directly to liver for incorporation into urea. 10. Describe three main strategies used to maintain plasma calcium levels within the normal range. State what effect parathyroid hormone has on each. Increase gut absorption PTH stimulates Vit D Increase kidney resorption of Ca (decrease excretion), PTH increases this Increase bone release of Ca PTH stimulates 7 of 7