MTC Mod 3

A 25-year-old man complains of dyspnea. He has a family history of lung disease developing at an early age. Physical examination shows inspiratory crackles and diminished breath sounds in the lower lobes of both lungs. A chest radiograph reveals enlargement of the air spaces in both lower lobes. A serum protein electrophoresis most likely shows which of the following? A. Absent α1-globulin peak B. Absent α2-globulin peak C. Absent β-globulin peak D. Flat γ-globulin peak E. Monoclonal spike

A. Absent α1-globulin peak The patient has α1-antitrypsin (AAT) deficiency, which is an autosomal recessive disorder. Serum protein electrophoresis shows absence of the α1-globulin peak, which is normally occupied by AAT, an antiprotease that destroys elastases produced by neutrophils. In the lungs, decreased production of AAT causes neutrophilic damage to the elastic tissue structure of the entire respiratory unit (respiratory bronchioles, alveolar ducts, and alveoli) in the lower lobes, which is known as panacinar emphysema. Air is trapped in the respiratory unit, causing permanent enlargement of the distal airways.

All of the following statements regarding the actions and inactivation of acetylcholine are true EXCEPT which one? A. Acetylcholine is inactivated by a reuptake mechanism operating in the presynaptic terminus. B. Acetylcholine is the neurotransmitter for the preganglionic neurons of the autonomic nervous system. C. Postganglionic acetylcholine receptors are classified pharmacologically as either nicotinic or muscarinic. D. Acetylcholine is inactivated by hydrolysis by acetylcholinesterase. E. Following synthesis in the presynaptic terminal, approximately one-half of the acetylcholine remains free in the cytoplasm.

A. Acetylcholine is inactivated by a reuptake mechanism operating in the presynaptic terminus. Ach is inactivated by Acetylcholinesterase.

A 65-year-old woman with acute myelogenous leukemia is going to be placed on remission chemotherapy. Which of the following drugs should be used to prevent urate nephropathy? A. Allopurinol B. Aspirin C. Probenecid D. Thiazides E. Sulfinpyrazone

A. Allopurinol The correct answer is A, allopurinol. Allopurinol is a xanthine oxidase inhibitor. In cancer patients this drug prevents excessive production of uric acid released from dying cancer cells. Excessive uric acid in the kidney may result in acute renal failure due to blockage of the renal tubules by urate crystals. Aspirin at low doses decreases uric acid in uric acid, and in high doses is uricosuric. Probenecid is a uricosuric drug that is used in treating underexcretors with gout. Thiazides can produce hyperuricemia by increasing proximal tubule reabsorption of uric acid and decreasing secretion of uric acid. Sulfinpyrazone is a uricosuric drug used to treat underexcretors with gout.

A compensatory mechanism to allow adequate oxygen delivery to the tissues at high altitudes, where oxygen concentrations are low, would be which of the following? A. An increase in 2,3-bisphosphoglycerate synthesis by the red cell B. A decrease in 2,3-bisphosphoglycerate synthesis by the red cell C. An increase in hemoglobin synthesis by the red cell D. A decrease in hemoglobin synthesis by the red cell E. Decreasing the blood pH

A. An increase in 2,3-bisphosphoglycerate synthesis by the red cell 2,3-bisphosphoglycerate favors the deoxy conformation of Hb. Therefore, increased concentrations of 2,3-BPG would allow more oxygen to be released in the tissues. See Marks' 4th edition, Chap 44, ques 1, page 965

All of the statements concerning vitamin B12 are CORRECT EXCEPT: A. B12 is primarily transported in the blood by binding to albumin. B. The Schilling test helps confirm a B12 deficiency. C. Absorption of B12 occurs in the terminal ileum. D. In B12 deficiency, urinary methyl malonate excretion increases. E. Removal of the stomach could lead to a deficiency of B12.

A. B12 is primarily transported in the blood by binding to albumin. The correct answer is A. Dietary B12 binds to R-binders (haptocorrins) in the stomach and then travels to the intestine, where R-binders are released and destroyed by pancreatic proteases. Free B12 binds to intrinsic factor (IF) (synthesized by parietal cells in the stomach) in the intestine. B12-IF complex travels to the terminal ileum and carried by proteins called transcobalamins (TC) to the liver, where B12 is stored.

A 30-year-old woman has just finished eating dinner. Which of the following rate-limiting enzymes is currently operative? A. Carbamoyl phosphate synthetase II B. Carnitine acyltransferase I C. Fructose 1,6-bisphosphatase D. Hormone-sensitive lipase E. Liver phosphorylase

A. Carbamoyl phosphate synthetase II The patient is in the fed state. Carbamoyl phosphate synthetase (CPS II) is the rate-limiting enzyme in pyrimidine synthesis, which occurs in the fed state. The enzyme is located in the cytosol and catalyzes the formation of carbamoyl phosphate from glutamine, CO2, and ATP.

A 66-year-old man has severe chest pain that radiates down the inside of his left arm. His medical history suggests chronic alcoholism, and the physical examination shows no neurological abnormalities, but laboratory results show macrocytic anemia with hyper-segmented neutrophils and mild pancytopenia. His plasma homocysteine concentration is increased, and an electrocardiography shows evidence of a prior acute anterior myocardial infarction. Decrease in which of the following best explains the increase in plasma homocysteine in this patient? A. Cystathionine synthase B. Thymidylate synthase C. Serum folate D. Dihydrofolate reductase E. Serum vitamin B12

A. Cystathionine synthase Alcoholism is the most common cause of folate deficiency due to poor diet that decreases liver stores of folate and decreases reabsorption of monoglutamate form of folate in the jejunum. Vitamin B12 removes the methyl group from N5 methyltetrahydrofolate (circulating form of folate) to produce methyl-vitamin B12 and tetrahydrofolate. The methyl group is transferred to homocysteine to produce methionine, and thus decrease in either N5-methyltetrahydrofolate or vitamin B12 results in increased plasma homocysteine concentration. An increase in plasma homocysteine leads to endothelial cell damage and potential vessel thrombosis that can have a role in the patient's acute myocardial infarction. Vitamin B12 deficiency produces neurologic abnormalities in the spinal cord and central nervous system. This patient has no neurologic symptoms. Decreased activity of cystathionine synthase is present in homocystinuria, a rare autosomal recessive disease. Cystathionine synthase catalyzes conversion of homocysteine to cystathionine. Dihydrofolate reductase converts oxidized dihydrofolate to tetrahydrofolate. Thymidylate synthase requires folate and converts deoxyribose uridine monophosphate to deoxyribose thymidine monophosphate.

A mother with an increase in serum α-fetoprotein gives birth to a child with a meningomyelocele. Which of the following supplement regimes could have prevented this malformation? A. Folic acid prior to pregnancy B. Prenatal vitamins throughout pregnancy C. Vitamin B6 (pyridoxine) prior to birth D. Vitamin B12 throughout pregnancy E. Vitamin C throughout pregnancy

A. Folic acid prior to pregnancy The correct answer is A. A meningomyelocele is an example of a neural tube defect and is characterized by a cystic mass that contains the spinal meninges and spinal cord. Neural tube defects are caused by failure of fusion of the lateral folds of the neural plate or rupture of a previously closed neural tube. In either case, the maternal α-fetoprotein is increased in serum and amniotic fluid. Dietary folic acid deficiency is associated with an increased risk of developing neural tube defects. Levels of folic acid must be adequate prior to pregnancy to prevent the defects.

The cytoplasmic chemical most responsible for controlling the concentration of methemoglobin in the red blood cell is: A. NADH. B. NADPH. C. ATP. D. 2,3-BPG. E. Ca2+.

A. NADH. NADH is used to reduce methemoglobin to hemoglobin. So, decreased concentrations of NADH would lead to increased concentrations of methemoglobin.

The choline of acetylcholine, a neurotransmitter, is obtained from which amino acid? A. Serine B. Alanine C. Tyrosine D. Tryptophan E. Lysine

A. Serine

Which of the following is involved in formation of deoxyribonucleotides from ribonucleotides? A. Thioredoxin B. Dihydrofolate reductase C. Hypoxanthine phosphoribosyl transferase D. 5phosphoribosyl1pyrophosphate E. Glutamine

A. Thioredoxin The conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphate is performed by ribonucleotide reductase (RR), which requires reduced thioredoxin to transfer NADPH derived hydrogen to 2' position of the ribose sugar.

The viscosity of the RBC membrane is decreased by: A. lowering the cholesterol content. B. increasing the percentage of saturated fatty acids in the membrane phospholipids. C. decreasing the temperature. D. increasing the chain length of the constituent fatty acids. E. replacing cis-unsaturated fatty acids with trans-unsaturated fatty acids.

A. lowering the cholesterol content. By lowering cholesterol content, the viscosity will decrease. All the other options would increase the viscosity.

A non-essential amino acid which serves as the biological precursor of the catecholamine neurotransmitters: A. tyrosine B. arginine C. leucine D. methionine E. tryptophan

A. tyrosine

Drugs are being developed that will induce the transcription of globin genes, which are normally silent in patients affected with sickle cell disease. A good target gene for such therapy in this disease would be which of the following? A. The a1-gene B. The a2-gene C. The g-gene D. The β-gene E. The x-gene

Answer Key: C Feedback: Incorrect. The correct answer is C. By turning on the g-gene (normally only present in fetal Hb), the defective beta-gene can be bypassed. See Marks' 4th edition, Chap 44, ques 3, page 965 for explanation.

A baby boy, born at term by normal vaginal delivery and initially well, develops tachypnea on the third day of life. Arterial blood gas results are: [H+] 50 nmol/L[34-46nmol/L, pH 7.36-7.44] (pH 7.30) [, pCO2 3.3 kPa [4.5 6.0kPa]. Urine is negative for reducing substances. He becomes progressively more acidotic, and the next day his plasma ammonia concentration is found to be very high. Which diagnosis is most likely? A. A urea cycle defect B. An organic acidemia C. Congenital hypothyroidism D. Galactosemia E. Respiratory distress syndrome (RDS)

B. An organic acidemia Organic acidemias can cause hyperammonemia as well as acidosis. Although hyperammonemia is characteristic of urea cycle defects, it is not unique to them, and patients with these conditions are not usually acidotic. There is nothing in the information provided to suggest the diagnosis of urea cycle deficit. Galactosemia can cause hepatic dysfunction and hence hyperammonemia, but a positive test for urinary reducing substances would be expected. Any severe systemic illness can cause hyperammonemia in the newborn, but RDS typically causes a respiratory acidosis as a result of carbon dioxide retention, and this acidosis is non-respiratory.

A 72-year-old male presents with a complaint of recent onset of difficulty in performing activities of daily living. Upon questioning, his spouse reveals that he "hasn't been able to get around the way he used to." Physical examination reveals a well-nourished man who walks with an exaggerated kyphosis. His gait appears to be quite slow and wide-based. He also appears to have a resting tremor. The appropriate management of his case would target which of the following? A. Amino acid degradation B. Catecholamine synthesis C. Ganglioside degradation D. Prostaglandin synthesis E. Sphingolipid degradation

B. Catecholamine synthesis The above case describes a patient with Parkinson's disease, which is caused by degeneration of the substantia nigra. This leads to dopamine deficiency in the brain and results in resting tremors, bradykinesia, cog-wheeling of the hand joints, and rigidity of musculature. Dopamine is one of the catecholamines synthesized in a common pathway with norepinephrine and epinephrine. The diseases involving amino acid degradation (choice A), ganglioside degradation (choice C), and sphingolipid degradation (choice E) do not match the presentation seen in the case.

A patient with adenocarcinoma is undergoing chemotherapy with 5-Fluorouracil and methotrexate at a standard dose. After two rounds of therapy, a CAT scan revealed that the tumor had grown, and the patient experienced no toxic effects of the chemotherapy. What enzyme is overexpressed in this patient's tumor and normal tissues, which may account for the ineffectiveness of chemotherapy? A. CTP synthetase B. Dihydropyrimidine dehydrogenase C. Thymidylate synthase D. Deoxycytidylate deaminase E. DNA polymerase

B. Dihydropyrimidine dehydrogenase The correct answer is B, dihydropyrimidine dehydrogenase. Overexpression of this enzyme in both the tumor and normal intestinal tissue would account for the ineffectiveness of 5-fluorouracil in inhibiting thymidylate synthase. Overexpression of CTP synthetase would produce more CTP that would inhibit CPS II and de novo pyrimidine synthesis, and thus this would inhibit tumor DNA synthesis and replication of normal intestinal epithelial cells. Increased synthesis of thymidylate synthase in tumor can account for tumor resistance to 5-FU, however this enzyme is rarely overexpressed in normal colon tissue, therefore the toxic effects of 5-FU would result in intestinal problems. Overexpression of deoxycytidylate deaminase produce dUMP, which would compete with 5-FU for conversion to dTMP. Overexpression of DNA polymerase can account for tumor growth, however overexpression in colon would present as a hyperproliferative intestinal disorder.

In the pathway for bilirubin breakdown, the deficiency of what enzyme leads to Crigler-Najjar syndrome, type I? A. Alkaline phosphatase B. Glucuronyl transferase C. Heme oxygenase D. Biliverdin reductase E. UDPG dehydrogenase

B. Glucuronyl transferase

Which finding most suggests that fluid depletion is due to predominant water loss rather than isotonic fluid loss? A. Elevated plasma urea concentration B. Highly concentrated urine C. Increased hematocrit D. Normal plasma sodium concentration E. Tachycardia

B. Highly concentrated urine Predominant water loss tends to raise plasma osmolality, triggering the secretion of vasopressin (antidiuretic hormone). This maximizes the reabsorption of water from the tubular fluid so that the urine becomes highly concentrated. Plasma urea concentration tends to rise with fluid loss of either type. A decrease in the glomerular filtration rate (GFR) is the main cause with isotonic loss and increased reabsorption of urea from the highly concentrated urine with predominant water loss. Hypernatremia suggests that water has been lost without a concomitant loss of sodium. Loss of isotonic fluid is born primarily by the extracellular compartment and (unless the fluid lost is blood) causes an early increase in hematocrit. Predominant water loss is borne by the whole body water compartment and has a lesser effect on the extracellular fluid volume.

A one-year-old male child is presented to the pediatrician because his parents have noticed that he is mutilating himself by chewing on his lips and hitting his head. A routine examination revealed that the child has signs of gouty arthritis and exhibits signs of mental retardation. Which of the following enzymes is most likely deficient in this child? A. Xanthine oxidase B. Hypoxanthine-guanine phosphoribosyltransferase C. Adenosine deaminase D. Phosphoribosylpyrophosphate aminotransferase

B. Hypoxanthine-guanine phosphoribosyltransferase

Consecutive repeat measurements of blood glucose concentration (all values in mmol/L) in a single blood sample, using the same point of care analyzer, are: 5.1, 4.9, 5.0, 5.0, 5.1, 5.0, 5.2, 5.1, 5.0, 5.1. On the basis of these data, which statement about the analyzer/method is most applicable? A. It has high accuracy. B. It has high precision. C. It is specific for glucose. D. It has high sensitivity. E. It has high specificity.

B. It has high precision. It is suitable for use by patients with diabetes to monitor their blood glucose concentrations. It should be capable of detecting hypoglycemia in patients even if they are asymptomatic. B is correct answer: Precision is a measure of the reproducibility of a measurement; these results fall within a very small range, indicating good precision.

The resting potential of a typical nerve cell membrane is determined primarily by a transmembrane equilibrium dominated by its permeability to: A. Na+. B. K+. C. Ca2+. D. both Na+ and K+. E. all three ions.

B. K+.

A 60-year-old man who has smoked cigarettes for the past 35 years develops a cough and weight loss. Physical examination reveals coarse inspiratory crackles in both lungs. A chest radiograph shows a centrally located mass in the left hilum. Laboratory studies show a serum sodium of 115 mEq/L (136-145 mEq/L). A sputum cytology reveals small, hyperchromatic cells and necrotic debris. Which of the following laboratory results is most likely present? Note: ADH, antidiuretic hormone; POsm, plasma osmolality. A. POsm decreased, serum ADH decreased B. POsm decreased, serum ADH increased C. POsm increased, serum ADH decreased D. POsm increased, serum ADH increased

B. POsm decreased, serum ADH increased A decrease in POsm and an increase in serum ADH occur in the syndrome of inappropriate ADH (SIADH). It is most often caused by ectopic secretion of ADH by a primary small cell carcinoma of the lung (left hilar mass; small, hyperchromatic cells in the sputum) in a patient who smokes cigarettes. Excess ADH causes increased reabsorption of free water, a dilutional hyponatremia (decreased POsm), and a concentrated urine (increased UOsm). The coarse inspiratory crackles are caused by increased mucus in the segmental bronchi and terminal bronchioles (chronic bronchitis).

In one form of severe combined immunodeficiency disease (SCID) an increase in one purine metabolite leads to inhibition of DNA synthesis by reducing the activity of which enzyme? A. PRPP synthase B. Ribonucleotide reductase C. Thymidine kinase D. Thymidylate synthetase

B. Ribonucleotide reductase A defect in adenosine deaminase leads to an accumulation of dATP which inhibits ribonucleotide reductase—inhibiting dNTP synthesis.

In the de novo synthesis of pyrimidine nucleotides: A. reactions take place exclusively in the cytosol. B. a free base is formed as an intermediate. C. PRPP is required in the rate-limiting step. D. UMP and CMP are formed from a common intermediate. E. UMP inhibition of OMP-decarboxylase is the major control point.

B. a free base is formed as an intermediate. The answer is B, which is in contrast with purine synthesis where the sugar is produced first and base built on sugar. Part of this process takes place in mitochondria. PRPP is required to convert orotate to OMP and is not rate limiting. OMP to UMP to CTP is a sequential process. UMP does inhibit OMP decarboxylase, but this is not the rate limiting step.

Serum isoenzyme measurements are useful in diagnosis because: A. the composition of the serum changes specifically with specific diseases. B. different tissues may contain different isoenzymes, and any damage to a particular tissue releases only its characteristic isoenzymes into serum. C. different tissues may have the same isoenzyme composition, and a given disease specifically releases only certain disease-specific isoenzymes into serum. D. the disease process causes the damaged tissue to synthesize and release specific isoenzymes as a defense mechanism specific for a given disease. E. isoenzyme measurements are expensive and are a good way for hospitals to increase their profits.

B. different tissues may contain different isoenzymes, and any damage to a particular tissue releases only its characteristic isoenzymes into serum.

The neurotransmitter acetylcholine is: A. synthesized by the enzyme choline esterase. B. hydrolyzed by the enzyme acetylcholine esterase at the synapse. C. synthesized in the adrenal medulla. D. the primary neurotransmitter in the brain. E. competitively inhibited by diisopropylfluorophosphate.

B. hydrolyzed by the enzyme acetylcholine esterase at the synapse.

As coproporphyrinogen III moves from the liver cytosol to the liver mitochondria and becomes protoporphyrinogen IX, A. protoporphyrinogen IX becomes more soluble in water because of oxidation of coproporphyrinogen III. B. protoporphyrinogen IX becomes less soluble in water because of oxidation of coproporphyrinogen III. C. protoporphyrinogen IX becomes more soluble in water because of reduction of coproporphyrinogen III. D. protoporphyrinogen IX becomes more soluble in lipids because of oxidation of coproporphyrinogen III. E. protoporphyrinogen IX becomes less soluble in lipids because of reduction of coproporphyrinogen III.

B. protoporphyrinogen IX becomes less soluble in water because of oxidation of coproporphyrinogen III.

Enzyme abnormalities that can lead to hyperuricemia and gout include: A. reduced activity of PRPP synthetase. B. reduced activity of xanthine oxidase. C. increased activity of hypoxanthine-guanine phosphoribosyltransferase. D. reduced activity of PRPP amidotransferase. E. reduced activity of IMP dehydrogenase.

B. reduced activity of xanthine oxidase. The correct answer is B, reduced activity of xanthine oxidase. This is why allopurinol is only useful prophylactically and can make an active attack of gout worse.

The formation of deoxyribonucleotides involves which of the following processes? A. reduction of ribose in monophosphates B. reduction of ribose in diphosphates C. reduction of ribose in triphosphates D. reduction of ribose in 5phosphoribosyl pyrophosphate (PRPP) and subsequent reaction with a purine or pyrimidine E. oxidation of ribose in diphosphates

B. reduction of ribose in diphosphates All ribonucleotides must be diphosphate nucleotides to be converted to deoxyribonucleotides

The distribution of inosine monophosphate (IMP) conversion to either guanosine monophosphate (GMP) or adenosine monophosphate (AMP) is regulated by: A. feedback inhibition of phosphoribosylamine formation by GMP and/or AMP. B. the requirement of GTP for AMP formation, and ATP for GMP formation. C. availability of phosphoribosyl pyrophosphate (PRPP). D. feedback inhibition of GMP on AMP formation and AMP on GMP formation.

B. the requirement of GTP for AMP formation, and ATP for GMP formation.

Transfer of the methyl group from 5methyl tetrahydrofolate to homocysteine to form methionine requires: A. NADPH. B. vitamin B12. C. FAD. D. pyridoxal phosphate. E. none of the above

B. vitamin B12. Recall, Vitamin B12 (also called cobalamin) is involved in two reactions in the body: 1, the transfer of a methyl group from N5-methyl-FH4 to homocysteine to form methionine (above), and 2, the rearrangement of L-methylmalonyl-CoA to form succinyl CoA,

Allopurinol is used in the treatment of gout by reducing the production of uric acid. In Lesch-Nyhan syndrome the decrease in uric acid is balanced by an increase in xanthine and hypoxanthine in the blood. However, in other forms of gout the decrease in uric acid is greater than the increase in xanthine and hypoxanthine in the blood. The explanation for this difference in the two forms of gout is: A. PRPP levels are reduced in Lesch-Nyhan. B. xanthine is salvaged to IMP which inhibits PRPP amidotransferase. C. in Lesch-Nyhan xanthine oxidase activity is reduced. D. in non-Lesch-Nyhan gout PRPP levels are reduced.

B. xanthine is salvaged to IMP which inhibits PRPP amidotransferase. A is incorrect because PRPP levels are increased in Lesch Nyhan due to decreased activity of HGPRTase. C is incorrect because in LeschNyhan, HGPRT activity is reduced. D is incorrect because in other forms of gout, PRPP levels are also increased.

In the metabolic pathway of heme biosynthesis, a deficiency in the enzyme ferrochelatase in a patient will result in which of the following? (Select 2 answers) A. An increase in urogen III cosynthase greater than normal in the patient B. A decrease in d-aminolevulinic acid greater than normal in the patient C. An increase in d-aminolevulinic acid synthase greater than normal in the patient D. An increase in d-aminolevulinic acid greater than normal in the patient E. Increased excretion of coproporphyrin I in the patient

Both C and D are correct. The lack of ferrochelatase will cause the heme synthesis pathway to back up, resulting in a buildup of d-aminolevulinic acid. Additionally, the lack of negative feedback from heme on ALA-synthase will result in greater than normal levels in this patient. Also, the excess precursors to heme (protoporphyrin) are not water-soluble and are not excreted, which leads to erythropoietic protoporphyrin's unique manifestations of photosensitivity. See this article for more information: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096108/

A 32-year-old alcoholic has fever, jaundice, and tender hepatomegaly. A liver biopsy exhibits fatty change, Mallory's bodies, and a neutrophilic infiltrate. UBG urine urobilinogen, % CB is conjugated bilirubin. What are the most likely values you would see in this patient? A. % CB <20, Urine Bilirubin negative, Urine UBG ↑↑, AST ↑, ALT normal, ALP normal, GGT normal B. % CB >50, Urine Bilirubin ↑↑, Urine UBG negative, AST ↑, ALT ↑, ALP ↑↑↑, GGT ↑↑↑ C. % CB 20-50, Urine Bilirubin ↑, Urine UBG ↑↑, AST ↑↑, ALT ↑, ALP ↑↑, GGT ↑↑↑ D. % CB 20-50, Urine Bilirubin ↑, Urine UBG ↑↑, AST ↑↑, ALT ↑↑↑, ALP ↑, GGT ↑ E. % CB <20, Urine Bilirubin negative, Urine UBG normal, AST normal, ALT normal, ALP normal, GGT normal

C. % CB 20-50, Urine Bilirubin ↑, Urine UBG ↑↑, AST ↑↑, ALT ↑, ALP ↑↑, GGT ↑↑↑ The patient has alcoholic hepatitis, which produces a mixed jaundice (CB 20-50%). Urine UBG is increased, because UBG that is normally recycled back to the liver is redirected into the urine. Serum transaminases are increased with serum AST (mitochondrial enzyme) greater than ALT (cytosol enzyme). Because AST is normally located in the mitochondria of hepatocytes, alcohol, a mitochondrial toxin, causes preferential release of AST into the blood. Serum ALP is slightly increased; however, serum GGT is markedly increased, because alcohol induces enzyme synthesis in the hepatocyte cytochrome P-450 system in the smooth endoplasmic reticulum. GGT is also located in the SER and is increased as well.

An infant has a history of recurrent bacterial and fungal infections. Serum protein analysis showed no gamma globulin and further tests showed an increase in the white cell concentration of dATP. Which of the following is the most likely diagnosis? A. Orotic aciduria B. AMP deaminase deficiency C. Adenosine deaminase deficiency D. Lesch-Nyhan syndrome

C. Adenosine deaminase deficiency Adenosine deaminase deficiency leads to severe combined immunodeficiency syndrome (SCIDS) characterized by the inability of T and B cells to proliferate during infection and death due to dATP accumulation.

The deoxyribose of dCDP is made most directly from: A. ribose 5-phosphate. B. ribulose 5-phosphate. C. CDP. D. PRPP. E. none of the above.

C. CDP.

A young woman undergoes investigation for Cushing's syndrome having presented with acne and oligomenorrhea. Early morning plasma cortisol concentration is 824 nmol/L [140-690 nmol/L]; plasma adrenocorticotropic hormone (ACTH) concentration is at the upper limit of the normal range. Early morning plasma cortisol concentration after taking dexamethasone 1 mg at midnight is 766 nmol/L. After taking dexamethasone 2.0 mg 6-hourly for 48 hours, plasma cortisol concentration is 40 nmol/L. What is the most likely diagnosis? A. Adrenal adenoma B. Adrenal carcinoma C. Cushing's disease (pituitary tumor secreting ACTH) D. Depression E. Ectopic secretion of ACTH by small cell carcinoma of bronchus

C. Cushing's disease (pituitary tumor secreting ACTH) Suppression of ACTH (and thus cortisol) secretion after a high dose of dexamethasone (2 mg 6-hourly for 48 hours) is characteristic of Cushing's disease, though can sometimes occur with ectopic secretion of ACTH, particularly by carcinoid tumors. The high-end normal early morning ACTH is also typical of Cushing's disease. ACTH secretion would be expected to be suppressed by the excess cortisol secreted by an adrenal adenoma; because they are not ACTH-dependent, cortisol secretion by adenomas is not usually suppressed by dexamethasone. Adrenal carcinoma is a rare cause of Cushing's syndrome, although, in women, virilisation can be a prominent clinical feature. However, ACTH secretion would be expected to be suppressed by the excess cortisol secreted by an adrenal carcinoma, and cortisol secretion is not suppressed by dexamethasone. Depression can cause an increase in cortisol secretion that is not suppressed by a single 1 mg dose of dexamethasone; suppression is, however, usual (though not invariable) following a 2-day high dose (2.0 mg) dexamethasone suppression test. ACTH (and thus cortisol) secretion is typically resistant to suppression by dexamethasone in ectopic ACTH secretion by carcinomas. This is, anyway, a very rare cause of Cushing's in younger people and less likely to cause virilisation of females.

Thrombin regulates two events that interrupt the normal clotting process. These are its interactions with which of the following? A. Blood platelets and lymphocytes B. Factors V and VII C. Factors Va and VIIIa D. Fibrinogen and tissue factor E. Factors IX and X

C. Factors Va and VIIIa Thrombin binds the thrombomodulin receptor and activates protein C. Protein C and S then destroy factors Va and VIIIa.

A febrile 54-year old alcoholic comes to the emergency room complaining of an inability to walk because his foot hurts. The night before he consumed a rather sumptuous meal and drank a large amount of alcohol. Physical examination is notable for a tender erythematous area with heat over the metatarsophalangeal joint. His breath has a fruity sweet odor, and he displays deep shallow breathing. He has been taking medication for swelling of the joints. His clinical values reveal: Which of the following enzymes involved in nucleotide metabolism is most likely the target of his current medication? A. Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) B. Orotate phosphoribosyltransferase (OPRTase) C. Xanthine oxidase D. Thymidine kinase E. Phosphoribosylpyrophosphate synthase (PRPP synthase)

C. Gout or hyperuricemia is treated with allopurinol.

42-year-old African American man is seen in the emergency room for a severe headache. His blood pressure is 180/110 mm Hg, and he has evidence of retinal hemorrhage. An infusion of nitroprusside (which metabolized to produce nitric oxide) is given. Which of the following enzymes is affected most directly by the active metabolite of this drug? A. Phospholipase A2 B. Cyclic AMP phosphodiesterase C. Guanylate cyclase D. Cyclic GMP phosphodiesterase E. Phospholipase C

C. Guanylate cyclase The correct answer is C. Nitroprusside is metabolized to produce nitric oxide. NO, normally produced by the vascular endothelium, stimulates the Guanylate cyclase in vascular smooth muscle to increase cGMP, activate protein kinase G, and cause vessel dilation.

A 45-year-old woman with rheumatoid arthritis has an increased serum total protein. The hyperproteinemia is most likely due to an increase in which of the following protein fractions? A. Albumin B. Immunoglobulin A C. Immunoglobulin G D. Immunoglobulin M

C. Immunoglobulin G An increased serum total protein is most often due to an increase in immunoglobulins (Igs). Igs are primarily increased in chronic inflammation and malignant plasma cell disorders (e.g., multiple myeloma). Because the patient has rheumatoid arthritis, a chronic inflammatory disease, the immunoglobulins are increased. The primary Ig to increase in chronic inflammation is IgG. A serum protein electrophoresis would show a polyclonal gammopathy (diffuse increase in the γ-globulin curve).

A 9-month-old infant is evaluated because of a 2-day history of incessant coughing with some vomiting after coughing bouts. Medical history shows no immunizations. On physical examination, the infant is in acute distress with a continual cough and an inspiratory whoop after each coughing episode. Radiography shows no evidence of epiglottitis. Which of the following best describes the biochemical basis for the clinical findings? A. Activation of a Gq protein B. Activation of a Gs protein C. Inactivation of a Gi protein D. Inhibition of tyrosine phosphorylation E. Stimulation of guanylyl cyclase activity

C. Inactivation of a Gi protein This infant has classic symptoms of infection with Bordetella pertussis, the etiologic agent in whooping cough. One of the toxins secreted by B. pertussis covalently modifies the Gi protein in respiratory phagocytes, leading to impaired function of the Gi protein and increased activity of cyclic adenosine monophosphate (cAMP). This action leads to ineffective phagocytosis and chemotaxis, and it inhibits lysosomal degradation of the bacteria. Pertussis is caused by inactivation of a Gi protein that produces a reduction in cAMP. By comparison, Gq proteins activate phospholipase C, producing the second messengers, diacylglycerol and inositol triphosphate. Pertussis is caused by inactivation of a Gi protein leading to a reduction of cAMP. Gs proteins, when activated, increase the concentration of cAMP. Pertussis involves the cAMP signaling pathway, while tyrosine phosphorylation, not affected in a whooping cough infection, is found in the insulin signaling pathway. Guanylyl cyclase, which produces cGMP from GTP, is not affected by the pertussis toxin.

A 55-year-old farmer has a raised crateriform lesion on the inner aspect of the bridge of his nose and numerous gray-white hyperkeratotic lesions on the face, hands, back of the neck, and forearms. Which of the following best characterizes the pathogenesis of these skin lesions? A. Cleavage of DNA strands B. Deficiency of DNA repair enzymes C. Increased production of pyrimidine dimers D. Point mutations with production of stop codons

C. Increased production of pyrimidine dimers Ultraviolet B (UVB) light (nonionizing radiation) is responsible for sunburns and the rapid increase of skin cancers in the United States. In this patient, the crateriform lesion on the nose is a basal cell carcinoma, the most common cancer caused by excessive UVB light exposure. The gray-white hyperkeratotic lesions in sun-exposed areas are actinic (solar) keratoses, which are precursors for squamous cell carcinoma of the skin. UVB light excites adjacent pyrimidine bases on DNA strands, causing them to form thymine-thymine dimers.

Isoforms of Z-bilirubin may be generated through photosensitizing the compound. Such isoforms are critical in the prevention of which pathology in bilirubin metabolism? A. Gilbert's syndrome B. Crigler-Najjar syndrome, type II C. Kernicterus D. Hepatitis A E. Dubin-Johnson disease

C. Kernicterus Kernicterus happens when too much bilirubin is produced and is absorbed in the brain tissue. All the other listed choices can produce too much bilirubin, but the deposition of bilirubin can be prevented if the bilirubin stays soluble and can be excreted. Photosensitizing the bilirubin can keep it soluble.

What enzyme(s) is/are mainly responsible for catabolism of serotonin? A. L-aromatic amino acid decarboxylase B. Catechol-O-methyl transferase (COMT) C. Monoamine oxidase D. Both A and B E. Both B and C

C. Monoamine oxidase

Which one of the following statements relating to the thymidylate (dTMP) synthase reaction is FALSE? A. dUMP is a substrate for this enzymatic reaction. B. A 1-carbon THF is a substrate for this enzymatic reaction. C. NADPH is a substrate for this enzymatic reaction. D. F-dUMP directly inhibits this enzymatic reaction. E. Dihydrofolate (DHF) is produced by this enzymatic reaction.

C. NADPH is a substrate for this enzymatic reaction.

Photosensitivity is a symptom of which porphyria(s)? A. PCT and CEP B. CEP C. PCT, CEP, EPP D. VP and EPP E. AIP

C. PCT, CEP, EPP

All the following are true about hemosiderin except? A. Hemosiderin is from iron that exceeds ferritin's storage capacity. B. Hemosiderin is composed of ferritin, denatured ferritin, and other substances. C. The iron within hemosiderin is readily available. D. Macrophages hold hemosiderin. E. Hemosiderin is often associated with hemorrhage.

C. The iron within hemosiderin is readily available.

Which enzyme functions in both the salvage of pyrimidine bases and in the de novo synthesis of pyrimidines? A. Carbamoyl phosphate synthetase II B. Dihydroorotase C. Orotate phosphoribosyltransferase D. Phosphoribosylamidotransferase E. Dihydrofolate reductase

C. This is the only enzyme that salvages pyrimidine bases and is involved in de novo synthesis of pyrimidines.

Conversion of fibrinogen to fibrin by thrombin in the coagulation cascade results in the production of: A. Factor X. B. Factor XIII. C. a soluble gel-like clot. D. excess Ca++. E. prothrombin.

C. a soluble gel-like clot. Fibrin forms a gel-like clot, factor XIII hardens the clot.

Therefore, allopurinol is a more effective treatment to reduce hyperuricemia in the non-Lesch-Nyhan patient because: A. allopurinol inhibits xanthine oxidase. B. allopurinol inhibits PRPP synthetase. C. allopurinol is converted to allopurinol ribose. D. allopurinol is converted to alloxanthine.

C. allopurinol is converted to allopurinol ribose. Since a non-Lesch-Nyhan patient still has use of HGPRT, allopurinol is converted by HGPRT to allopurinol ribose which can inhibit PRPP aminotransferase and halt purine de novo synthesis.

Elevated homocysteinemia affects vascular structure by altering the structure of: A. hemoglobin. B. albumin. C. collagen. D. blood clotting zymogens. E. chymotrypsin.

C. collagen. High homocysteine will alter the structure or collagen, which will affect vascular structure.

Methotrexate is normally given with 5-fluorouracil in chemotherapy, and is also given to patients with severe inflammation as seen in gout and arthritis. What effect does methotrexate have on nucleotide metabolism? A. inhibits purine catabolism B. inhibits pyrimidine catabolism C. inhibits purine de novo synthesis D. inhibits purine salvage E. inhibits pyrimidine de novo synthesis

C. inhibits purine de novo synthesis

All of the following are compounds that are products of tyrosine metabolism EXCEPT which one? A. melanin B. norepinephrine C. melatonin D. thyroxine E. acetoacetic acid

C. melatonin

What enzyme functions to convert N5,N10methyleneFH4 to N5 methylFH4, which serves as a methyl donor of Vitamin B12 cofactor in conversion of homocysteine to methionine by methionine synthase? A. serine hydroxymethyltransferase B. methylene synthase C. methylene FH4 reductase D. glycine cleavage enzyme E. dihydrofolate reductase

C. methylene FH4 reductase

The index which indicates that an anemia is caused by impaired production or RBCs rather than excessive destruction is: A. total bilirubin. B. hematocrit. C. reticulocyte count. D. blood hemoglobin. E. RBC count.

C. reticulocyte count. The amount of immature RBC will allow you to determine if an adequate number of RBC are being produced. If the correct number of immature RBC are being produced, you know that RBC are being degraded prematurely.

Which of the following is the rate-limiting enzyme in catecholamine biosynthesis? A. phenylalanine hydroxylase B. phenylethanolamine N-methyltransferase C. tyrosine hydroxylase D. DOPA decarboxylase E. catechol-o-methyl transferase

C. tyrosine hydroxylase

Patients with nephrotic syndrome have deficiencies of most plasma proteins, but one plasma protein fraction actually is increased. This fraction is: A. albumin. B. α1-Globulin. C. α2-Globulin. D. β-Globulin. E. γ-Globulin.

C. α2-Globulin. The presence or proteinuria, hypoproteinemia and edema constitute the nephrotic syndrome. Edema is in part due to redistribution of ECF between the vascular and interstitial compartments and secondary aldosteronism, with evidence of potassium depletion. Protein loss of albumin and other plasma proteins, such as hormone binding proteins, transferrin, and antithrombin II, are reduced with other large molecular weight protein increase in concentration, α2-macroglobulin, apoliproteins and coagulation factors (fibrinogen, Factor VIII, etc).

An obese 19-year-old man has a free health screen arranged by his employer. Apart from fairly frequent headaches, he is well. The results of liver function tests include a serum aspartate aminotransferase (AST) activity of 72 U/L [0-35U/L]; total bilirubin concentration and alkaline phosphatase and γ-glutamyl transferase activities are within normal limits. His fasting blood glucose concentration is 6.9 mmol/L [3-6mmol/L]. What is the most likely cause of the elevated AST? A. Early viral hepatitis B. Excessive alcohol ingestion C. Gallstones D. Non-alcoholic steatohepatitis E. Therapeutic use of aspirin

D. This is the most common cause of an isolated increase in serum aminotransferase activity, particularly in overweight and obese subjects. Although γ-glutamyl transferase activity is also usually elevated, it is not always so, and impaired glucose tolerance is a recognized consequence of obesity. Viral hepatitis would not present with normal bilirubin concentration, alkaline phosphatase and gammaglutamyl transferase. Excessive alcohol consumption would not explain the elevated glucose and normal values of other liver enzymes. Gallstones do not explain the elevated AST level. Aspirin does not explain the elevated blood glucose.

Plasma proteins released from damaged tissues provide a diagnostic tool in not only identifying the tissue that is damaged, but also as a marker of the severity of tissue damage. Of the plasma proteins released from the damaged liver, an increase in which protein's enzymatic activity would be the best indicator of the most cell destruction? A. Alanine aminotransferase (ALT) B. Υ-glutamyl transferase (GGT) C. Alkaline phosphatase (ALP) D. Aspartate aminotransferase (AST) E. 5' nucleotidase (5'NT)

D. Aspartate aminotransferase (AST) Both alanine and aspartate aminotransferase are found primarily in liver and muscle, while GGT is found in liver and kidney. ALP is found in bone and liver bile duct epithelial cells, while 5'nucleotidase is found on most cells that uptake nucleoside from blood for nucleotide synthesis. Elevated levels of AST would indicate the most cell damage since this enzyme is found not only in the cytosol but also the mitochondria of liver and muscle cells.

Receptors for the inhibitory neurotransmitters GABA and glycine: A. are ligand-gated anion channels. B. are ligand-gated cation channels. C. permit hyperpolarization of neuronal cell membranes. D. Both A and C are correct. E. Both B and C are correct.

D. Both A and C are correct.

A 50-year-old man who has a 10-year history of alcohol abuse complains of chest pain with radiation of the pain down the inner aspect of his left arm. An electrocardiogram shows an acute anterior myocardial infarction. A complete blood cell count reveals a macrocytic anemia with hypersegmented neutrophils and mild pancytopenia. No neurologic abnormalities are present on physical examination. The plasma homocysteine is increased. Which of the following best explains the mechanism for the increase in plasma homocysteine? A. Decreased activity of cystathionine synthase B. Decreased activity of dihydrofolate reductase C. Decreased activity of thymidylate synthetase D. Decreased serum folic acid E. Decreased serum vitamin B12

D. Decreased serum folic acid The most common cause of folic acid deficiency is alcoholism. Mechanisms for the deficiency include a poor diet leading to decreased liver stores of the vitamin and decreased reabsorption of the monoglutamate form of folate in the jejunum. Vitamin B12 (cobalamin) removes the methyl group from N5-methyltetrahydrofolate (circulating form of folic acid) to produce methyl-B12 and tetrahydrofolate. The methyl group is then transferred to homocysteine to produce methionine. Therefore a decrease in either N5-methyltetrahydrofolate or vitamin B12 causes an increase in the plasma homocysteine levels. Since there are no neurologic findings present, the most likely diagnosis is folic acid deficiency rather than vitamin B12 deficiency, which is associated with neurologic abnormalities in the spinal cord and central nervous system. An increase in plasma homocysteine damages endothelial cells and is a risk factor for coronary artery thrombosis.

A 70-year-old man is in hypovolemic shock resulting from a ruptured abdominal aortic aneurysm. Which of the following is a reversible cellular event that is most likely to occur in the straight portion of the proximal tubular cells of the kidneys? A. Activation of phospholipase in the cell membrane B. Diffusion of calcium into the cytosol C. Diffusion of cytochrome c out of the mitochondria D. Diffusion of sodium and water into the cytosol E. Increase in intracellular pH

D. Diffusion of sodium and water into the cytosol Blood loss due to a ruptured abdominal aortic aneurysm causes tissue hypoxia (inadequate oxygenation of tissue). The straight portion of the proximal tubule is the most sensitive portion of the nephron to hypoxia. The lack of oxygen in blood in hypovolemic shock causes a decrease in ATP synthesis in the mitochondria, which adversely affects the Na+/K+-ATPase pump by allowing Na+ and H2O to enter the cytosol. This produces swelling of the cell, which is reversible if oxygen is restored to the cell.

A patient was given a standard dose of 5-fluorouracil with no reduction in tumor size. The reduced level of 5-fluorouracil in the serum and increased levels of fluoro-alanine in the urine suggest that this patient has increased activity of which enzyme? A. Ribonucleotide reductase B. Dihydrofolate reductase C. Thymidylate synthase D. Dihydropyrimidine dehydrogenase E. OMP decarboxylase

D. Dihydropyrimidine dehydrogenase This enzyme is polymorphically expressed in the human population. In individuals undergoing treatment for cancer with the uracil analogue 5' Fluorouracil, the efficacy of treatment is largely determined by the activity of this enzyme. High metabolizers do not benefit from 5-fluorouracil chemotherapy while individuals with low activity of DPD can experience increased toxicity.

The reaction of hypoxanthine and PRPP (5'-phosphoribosyl pyrophosphate) leads directly to the formation of: A. XMP. B. AMP. C. GMP. D. IMP. E. XDP.

D. IMP.

Which statement is true of familial hypercholesterolemia? A. It is associated with decreased plasma concentrations of high density lipoprotein (HDL) cholesterol. B. It is caused by an abnormality in apolipoprotein B-100. C. It is caused by increased hepatic secretion of very low density lipoprotein (VLDL). D. It is characterized by decreased clearance of low density lipoprotein (LDL) from the plasma. E. It is inherited as an autosomal recessive trait.

D. It is characterized by decreased clearance of low density lipoprotein (LDL) from the plasma. Familial hypercholesterolemia is caused by any one of many mutations that reduce the expression or activity of the LDL receptor, thus decreasing cellular uptake of LDL from the plasma. Familial hypercholesterolemia is not associated with a change in serum HDL levels and is autosomal dominant. Lipoprotein B100 abnormalities are more associated with abetalipoproteinemia. Type IV hypertriglyceridemia is associated with increased hepatic secretion of VLDL.

The resting membrane potential (membrane polarization) of the neuron can be attributed, in part, to the relatively low permeability of the membrane to which cation? A. Ca2+ B. K+ C. Mg++ D. Na+ E. SO4-

D. Na+

A mature blood cell that lacks a nucleus is which of the following? A. Lymphocyte B. Basophil C. Eosinophil D. Platelet E. Neutrophil

D. Platelet

Acute intermittent porphyria results from lack of which enzyme? A. Uroporphyrinogen decarboxylase B. Protoporphyrinogen oxidase C. ALA synthase D. Porphobilinogen deaminase E. Ferrochelatase

D. Porphobilinogen deaminase

S-Adenosyl methionine is required for which conversion? A. tyrosine ® dihydroxyphenylalanine (L-DOPA) B. L-DOPA ® dopamine C. tryptophan ® serotonin D. norepinephrine ® epinephrine E. dopamine ® norepinephrine

D. SAM is needed as a methyl donor in this reaction.

What is the rate-limiting factor in the synthesis of acetylcholine? A. The activity of choline acetyltransferase B. The availability of acetyl-CoA C. The activity of acetylcholinesterase D. The availability of choline E. The activity of butyrylcholinesterase

D. The availability of choline

A family has two children, one with a mild case of thalassemia, and a second with a severe case of thalassemia, requiring frequent blood transfusions as part of the treatment plan. One parent is of Mediterranean descent, the other is of Asian descent. Neither parent exhibits clinical signs of thalassemia. Both children express 20% of the expected level of β-globin; the more severely affected child expresses normal levels of a-globin, whereas the less severely affected child only expresses 50% of the normal levels of a-globin. Why is the child who has a deficiency in a-globin expression less severely affected? A. Thalassemia is caused by a mutation in the a-gene, and the more severely affected child expresses more if it. B. The less severely affected child must be synthesizing the x-gene to make up for the deficiency in a-chain synthesis. C. The more severely affected child also has HPFH. D. The more severely affected child produces more inactive globin tetramers than the less severely affected child. E. Thalassemia is caused by an iron deficiency, and when the child is synthesizing normal levels of a-globin, there is insufficient iron to populate all of the heme molecules synthesized.

D. The more severely affected child produces more inactive globin tetramers than the less severely affected child.

A 2-year-old female infant is weak, lethargic and anemic, and her height and weight are low for her age. Her urine contains elevated levels of orotic acid, and the activity of uridine monophosphate synthase is low. The administration of which of the following will most likely alleviate her symptoms? A. Adenine B. Hypoxanthine C. Thymidine D. Uridine E. Guanine

D. Uridine The correct answer is D, Uridine, because the increased excretion of orotic acid and low activity or UMP synthase suggest that the patient has orotic aciduria. Deficiencies in one or both catalytic domains of UMP synthase result in the patient being unable to synthesize pyrimidines. Uridine bypasses the missing activity and can be salvaged to UMP that can also be converted to other pyrimidine nucleosides. Thymidine cannot be demethylated and converted to other pyrimidines. Hypoxanthine, adenine and guanine are all purine bases and, therefore, cannot be converted to pyrimidines

Which one of the following sets of three vitamins would be the MOST EFFECTIVE in reducing homocysteine levels in blood? A. Vitamin B6, biotin, thiamine B. Vitamin B12, lipoamide, pantothenic acid C. Folic acid, vitamin E, niacin D. Vitamin B6, vitamin B12, folic acid E. Riboflavin, vitamin K, vitamin B

D. Vitamin B6, vitamin B12, folic acid A high level of homocysteine in the blood raises the risk for heart disease. Two mechanisms of reducing homocysteine levels via three vitamins include the following: Homocysteine can be re-methylated to methionine: Homocysteine + methyl-cobalamin (where methyl group comes from folic acid) → methionine, catalyzed by methionine synthase. Homocysteine can be condensed with serine to form cystathionine: Homocysteine + B6 → cystathionine (catalyzed by cystathionine ß-synthase); cystathionine + B6 → cysteine.

In the normal blood clotting cascade, many of the various coagulation factors must be carboxylated in order for them to bind to phospholipid surfaces and participate in subsequent reactions leading to fibrin formation. The action of which specific vitamin is required for these carboxylation events? A. Vitamin C B. Vitamin B C. Vitamin D D. Vitamin K E. Vitamin E

D. Vitamin K Vitamin K is needed for γ‐carboxylation of factors II, VII, IX, and X.

Hereditary orotic aciduria is characterized by severe anemia, growth retardation, and high levels of orotic acid excretion. The defect may be either orotate phosphoribosyl transferase, orotidine decarboxylase, or both. The preferred treatment is dietary uridine, which reverses anemia and decreases the formation of orotic acid. Elements involved in the effectiveness of the dietary treatment include: A. conversion of uridine to UMP by uridine phosphotransferase. B. UTP from exogenous uridine provides substrate for synthesis of CTP. C. inhibition of carbamoyl phosphate synthetase II by UTP. D. all of the above. E. none of the above.

D. all of the above. Exogenous uridine requires conversion to monophosphate and ultimately UTP. The cell is deficient in UTP and CTP because the conversion of orotic acid is blocked, however the blocked and bypassed by uridine, which is converted to UTP that inhibits CPSII.

GABA (gamma-aminobutyrate), a neurotransmitter of inhibitory neurons, is synthesized by: A. transamination of alpha-ketobutyrate. B. carboxylation of alanine. C. deamination of glutamine. D. decarboxylation of glutamate. E. decarboxylation of aspartate.

D. decarboxylation of glutamate.

Gout is a disease characterized by hyperuricemia from overproduction of purine nucleotides. All of the following reactions or conditions can lead to hyperuricemia, EXCEPT: A. increased activity of the pentose monophosphate pathway. B. decreased activity of HGPRTase. C. increased consumption of protein. D. increased allosteric inhibition of PRPP synthetase.

D. increased allosteric inhibition of PRPP synthetase. If PRPPs synthetase is inhibited, no new purine nucleotides will be made. A will increase purine nucleotide synthesis. B will cause hyperuricemia. C will cause hyperuricemia by increasing purine nucleotide synthesis.

During a routine checkup of an asymptomatic middle-aged woman, her level of haptoglobin is found to be extremely low. Other blood values are normal. This finding could indicate: A. chronic damage to skeletal muscle. B. either acute liver damage or biliary obstruction. C. an acute-phase response. D. mild chronic hemolysis. E. multiple myeloma.

D. mild chronic hemolysis. Haptoglobin is an α2-globulin and functions to bind free hemoglobin released into the plasma during intravascular hemolysis. The haptoglobin-Hb complex is removed by the reticuloendothelial system, thereby conserving iron, and the concentration of haptoglobin falls correspondingly. Low concentrations are also due to chronic liver disease, metastatic disease and severe sepsis. Haptoglobin is an acute phase protein increased by cytokines, tumor necrosis factor and vasoactive substances.

The correct biosynthetic pathway from tyrosine to epinephrine is: A. tyrosine ® dopamine ® dopa ® norepinephrine ® epinephrine. B. tyrosine ® dopamine ® dopa ® epinephrine. C. tyrosine ® dopamine ® norepinephrine ® epinephrine. D. tyrosine ® dopa ® dopamine ® norepinephrine ® epinephrine. E. tyrosine ® dopa ® dopamine ® epinephrine.

D. tyrosine ® dopa ® dopamine ® norepinephrine ® epinephrine.

Which of the following is the major excretory by-product of the catabolism of norepinephrine? A. Normetanephrine B. 3,4-Dihydroxymandelic acid C. 3-Methoxy, 4-hydroxyphenylacetic acid D. 3-Methoxy, 4-hydroxyphenylglycol E. 3-Methoxy, 4-hydroxymandelic acid

E. 3-Methoxy, 4-hydroxymandelic acid The correct answer is E. NE is degraded by COMT or MAO. Methylation and oxidation may occur in any order. Methylated and oxidized derivatives of norepinephrine and epinephrine are produced, and 3-methoxy-4-hydroxymandelic acid is the final product. These compounds are excreted in the urine.

Carbamoyl phosphate is a key substance in: A. purine biosynthesis. B. pyrimidine biosynthesis. C. urea biosynthesis. D. A and B. E. B and C.

E. B and C.

The hydrophilic character of which of the following in bilirubin catabolism enables it to be water soluble, cross the canalicular membrane and enter bile? A. Z-bilirubin B. Urobilinogen C. Photobilirubin-EZ D. Urobilin E. Bilirubin diglucuronide

E. Bilirubin diglucuronide

Of the following enzymes involved in nucleotide metabolism, which is correctly paired with its pharmacological inhibitor? A. Xanthine oxidase-probenecid B. Thymidylate synthase-hydroxyurea C. Ribonucleotide reductase-5-fluorouracil D. IMP dehydrogenase-allopurinol E. Dihydrofolate reductase-methotrexate

E. Dihydrofolate reductase-methotrexate Methotrexate interferes with folate metabolism by acting as a competitive inhibitor of dihydrofolate reductase, which starves cells of tetrahydrofolate and thus is unable to synthesize purine and dTMP. Ribonucleotide reductase is inhibited by hydroxyurea, while thymidylate synthase is inhibited by 5-fluorouracil. Probenecid increases renal excretion of urate and does not inhibit production. Xanthine oxidase is inhibited by allopurinol.

The interaction between fibrinogen and thrombin produces an unstable network of fibrin as an initial blood clotting product. What coagulation factor will induce fibrin crosslinking to promote clot stability? A. Factor V B. Factor Va C. Factor VIII D. Factor XIII E. Factor XIIIa

E. Factor XIIIa Activated Factor XIIIa induces fibrin crosslinking.

The drug methotrexate is used as a therapy for rheumatoid arthritis, and has the side effects related to a competitive inhibition of dihydrofolate reductase. These side effects can be decreased by giving leucovorin (folinic acid), which is an active form of folic acid, 5-formyl THF that does not require DHF reductase. However, what would happen if this patient treated with methotrexate is given sufficient folate? A. DHF reductase will have same Km for dihydrofolate as it would in the absence of methotrexate. B. DHF reductase will have high Vmax than it would in the absence of methotrexate. C. DHF reductase will have a lower Km for dihydrofolate. D. DHF reductase will increase its affinity for methotrexate. E. DHF reductase will have the same Vmax as it would in the absence of methotrexate. F. DHF reductase will have a higher Km for dihydrofolate.

E. Folate (as 7,8 dihydrofolate) is converted to tetrahydrofolate by DHF reductase. Methotrexate is a competitive inhibitor of DHF reductase, therefore providing sufficiently high concentrations of folate will allow enzyme to reach same Vmax as obtained in the absence of the inhibitor.

Which of these coagulation factors DOES NOT have serine protease activity? A. Factor II (prothrombin) B. Factor VII C. Factor X D. Factor XII E. Protein S

E. Protein S

A 30-year-old woman has a macrocytic anemia with hypersegmented neutrophils. Additional history is not available. Physical examination reveals decreased vibratory sensation in the lower extremities. Which of the following is a potential cause of these findings? A. Alcohol abuse B. Oral contraceptives C. Phenytoin D. Pregnancy E. Terminal ileal disease

E. Terminal ileal disease The correct answer is E. Vitamin B12 and folic acid are both involved in DNA synthesis. Deficiency of either vitamin produces a macrocytic anemia with hypersegmented neutrophils. However, vitamin B12 is also involved in the conversion of methylmalonyl CoA to succinyl CoA in odd chain fatty acid metabolism. Deficiency of vitamin B12 causes a buildup of methylmalonyl CoA and its precursor, propionyl CoA, leading to demyelination in the posterior column and lateral corticospinal tract of the spinal cord. Decreased vibratory sensation occurs in posterior column disease, while muscle spasticity is seen in lateral corticospinal tract disease. In vitamin B12 metabolism, intrinsic factor produced by parietal cells in the stomach complexes with vitamin B12 in the duodenum. The complex is then reabsorbed in the terminal ileum. Therefore terminal ileal disease (e.g., Crohn's disease) is a cause of vitamin B12 deficiency.

Serum obtained from a blood specimen from a 52-year-old man with pancreatitis is noticed to be uniformly turbid. After standing in a refrigerator overnight, the appearance is unchanged. Which lipoprotein is most likely to be present in excess? A. Chylomicrons B. High density lipoproteins (HDL) C. Intermediate density lipoproteins (IDL) D. Low density lipoproteins (LDL) E. Very low density lipoproteins (VLDL)

E. Very low density lipoproteins (VLDL) VLDL have the same density as plasma and remain in suspension. An increase in plasma VLDL is a frequent finding in acute pancreatitis. Chylomicrons are less dense than plasma and float to the surface. HDL particles are too small to scatter light and do not cause the plasma to appear turbid. IDL are only slightly denser than plasma and can remain in suspension but are an uncommon cause of plasma turbidity. LDL particles are too small to scatter light and do not cause the plasma to appear turbid.

This enzyme first recognizes allopurinol as a substrate and is then inhibited by the product of enzyme catalysis. A. PRPP synthase B. HGPRT (hypoxanthine-guanine phosphoribosyl transferase) C. Adenosine deaminase D. PRPP amidotransferase E. Xanthine oxidase

E. Xanthine oxidase

A common intermediate in the biosynthesis of both purine and pyrimidine nucleotides is: A. hypoxanthine. B. phosphoribosylamine. C. inosinic acid. D. orotidine 5-phosphate. E. phosphoribosyl pyrophosphate (PRPP).

E. phosphoribosyl pyrophosphate (PRPP).

What would happen to DHF reductase if this patient on methotrexate was given folinic acid? A. DHF reductase will have same Km for dihydrofolate as it would in the absence of methotrexate. B. DHF reductase will have high Vmax than it would in the absence of methotrexate. C. DHF reductase will have a lower Km for dihydrofolate. D. DHF reductase will increase its affinity for methotrexate. E. DHF reductase will have the same Vmax as it would in the absence of methotrexate. F. DHF reductase will have a higher Km for dihydrofolate.

F. DHF reductase will have a higher Km for dihydrofolate. Folinic acid bypasses DHF reductase supplying THF, therefore the methotrexate would compete with endogenous folate for catalytic site of DHF reductase thus increasing enzyme Km.

Which reaction (A-I) produces the common methylating agent, SAM?

The correct answer is A. SAM participates in the synthesis of many compounds that contain methyl groups. It is used in reactions that add methyl groups to either oxygen or nitrogen. SAM is synthesized from methionine (knowing its full name, S-adenosylmethionine may clue you in) by adding ATP to methionine, demonstrated in reaction A.

A febrile 54-year-old alcoholic comes to the emergency room complaining of an inability to walk because his foot hurts. The night before he consumed a rather sumptuous meal and drank a large amount of alcohol. Physical examination is notable for a tender erythematous area with heat over the metatarsophalangeal joint. His breath has a fruity sweet odor, and he displays deep shallow breathing. He has been taking medication for swelling of the joints. His clinical values reveal: The high ß-hydroxybutyrate to acetoacetate ratio of 8 is due to: A. high NAD+/NADH ratio in the cytosol. B. low NAD+/NADH ratio in the mitochondria. C. high NAD+/NADH ratio in the mitochondria. D. low NAD+/NADH ratio in the cytosol. E. regeneration of NAD+ by pyruvate conversion to lactate.

The correct answer is B. The low ratio of NAD+ to NADH in mitochondria leads to the conversion of acetoacetate into betahydroxybutyrate in alcoholic ketoacidosis.

A 35-year-old man has acute myelogenous leukemia. He is currently being treated with multiple antileukemic agents. One week into therapy, he develops oliguric renal failure with an increase in serum blood urea nitrogen, creatinine, and uric acid. A urinalysis reveals an acid pH, and numerous crystals are present on sediment examination. Which of the following best explains the mechanism for the renal failure? A. Drug nephrotoxicity B. Increased degradation of purine nucleotides C. Increased degradation of pyrimidine nucleotides D. Leukemic infiltration of the kidneys

The correct answer is B. Treatment of disseminated malignancies like acute myelogenous leukemia causes the release of purine nucleotides from the nuclei of the killed cancer cells. Uric acid is the end-product of degradation of purine nucleotides. An acid urine pH causes uric acid to form crystals in the tubules of the nephron leading to renal failure. This complication is prevented by allopurinol, which blocks xanthine oxidase and prevents the conversion of xanthine to uric acid.

A febrile 54-year-old alcoholic comes to the emergency room complaining of an inability to walk because his foot hurts. The night before he consumed a rather sumptuous meal and drank a large amount of alcohol. Physical examination is notable for a tender erythematous area with heat over the metatarsophalangeal joint. His breath has a fruity sweet odor, and he displays deep shallow breathing. He has been taking medication for swelling of the joints. His clinical values reveal: Which of the following findings best describes the pathophysiologic process underlying these findings? A. Increased activity of HGPRTase B. Increased activity of xanthine oxidase C. Decreased renal excretion of uric acid D. Decreased PRPP amidotransferase activity E. Decreased activity of glucose-6-phosphate dehydrogenase activity

The correct answer is C. Based on the lab values, this is the only possible answer. If A was increased, uric acid would be lower. Uric Acid would be higher if B was increased. D is incorrect, because creatinine is elevated. If E was true, blood sugar would be much lower.

A febrile 50-year-old man with a 10-year history of alcohol abuse complains of pain in his left big toe. Physical examination reveals erythema and heat over the metatarsophalangeal joint. A complete blood cell count shows an absolute neutrophilic leukocytosis with greater than 10% band neutrophils in a 100 cell count. A synovial tap is performed and shows needle-shaped crystals phagocytosed by neutrophils. What is the mechanism for the joint inflammation? A. Decreased activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) B. Decreased activity of xanthine oxidase C. Decreased renal excretion of uric acid D. Increased degradation of pyrimidines E. Increased activity of phosphoribosyl-pyrophosphate synthetase

The correct answer is C. The patient has acute gouty arthritis involving the metatarsophalangeal joint of the left big toe. The presence of negatively birefringent crystals in synovial fluid is diagnostic of gout. Most cases of gout result from underexcretion of uric acid in the proximal tubules of the kidneys. Gout is commonly seen in patients with alcohol abuse because of the increase in synthesis of lactic acid and β-hydroxybutyric acid, which compete with uric acid for excretion in the proximal tubules. In the metabolism of alcohol, NADH, acetate, and acetyl CoA are metabolic end-products. The increase in NADH increases the conversion of pyruvate to lactate by lactate dehydrogenase. Acetyl CoA is utilized by the liver to synthesize ketone bodies. The excess in NADH causes acetoacetate to convert to β-hydroxybutyric acid.

A 2-year-old boy of normal weight and height is brought to a clinic because of excessive fatigue. Blood work indicates an anemia, with microcytic hypochromic red cells. The boy lives in a 100-year-old apartment building and has been caught ingesting paint chips. His parents indicate that the child eats a healthy diet and takes a Flintstones vitamin supplement every day. His anemia is most likely attributable to a deficiency in which of the following? A. Iron B. Vitamin B12. C. Folate D. Heme E. Vitamin B6.

The correct answer is D. Lead poisoning interrupts heme synthesis at the ALA-dehydratase and ferrochelatase steps. Marks' 4th edition, Chap 44, ques 2, page 965

Which reaction (A-I) is adenosylcobalamin dependent?

The correct answer is I. Vitamin B12 (also called cobalamin) is involved in two reactions in the body: 1, the transfer of a methyl group from N5-methyl-FH4 to homocysteine to form methionine, and 2, shown above, the rearrangement of L-methylmalonyl-CoA to form succinyl CoA, reaction I.