Bio chem Enz contd 8-2

Question 1

This patient presents with arthralgias and evidence of self-mutilation. Together with his mother’s report of orange granules in his diaper, this patient most likely has?

Answer 1

Lesch-Nyhan syndrome, a rare X-linked genetic disease caused by a deficiency of the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme. Defects in the HGPRT enzyme result in the accumulation of uric acid in all body fluids (ie, synovial fluid), which explains the patient’s swollen joints. Yellow-orange urate crystals (as found in the diaper) represent a classic finding of Lesch-Nyhan. Patients with this syndrome also present with episodes of self-mutilation, disordered movement, gout, and intellectual disability.

Question 2

Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by intellectual disability, self-mutilation behaviors, gout, and disordered movement. It is caused by a lack in hypoxanthine-guanine phosphoribosyltransferase, an enzyme in the purine salvage pathway. This results in an accumulation of uric acid and the poor utilization of folate and/or vitamin B12, which can lead to megaloblastic anemia, evidenced by ?

Answer 2

hypersegmented neutrophils on blood smear.

Question 3

he other answer options are incorrect: acanthocytes (spur-shaped red blood cells) are typically seen in those with abetalipoproteinemia and long-standing liver disease.
Elliptocytosis represents a hereditary dysfunction in red blood cell (RBC) membrane proteins. Basophilic stippling describes an ?

Answer 3

aggregation of residual ribosomes around the periphery of the RBCs and is commonly associated in cases of lead poisoning.

Schistocytes are RBCs that have a torn appearance because they have been shorn apart, as in microangiopathic hemolytic anemia. Target cells or codocytes are seen in thalassemias, liver disease, iron deficiency, and postsplenectomy conditions.

Tear-drop cells are seen in myelofibrosis, a condition in which RBCs squeeze out of a fibrotic bone marrow, giving the cells their distinctive shape.

Question 4

This patient has progressive intellectual disability, marfanoid habitus (tall and thin, elongated limbs, scoliosis), and subluxation of the ocular lens (ectopia lentis). Elevated homocysteine levels in blood and urine are diagnostic of?

Answer 4

homocystinuria. Multiple types of homocystinuria exist, depending on the deficient enzyme: cystathionine synthase or methionine synthase. It can also occur as a result of decreased affinity of cystathionine synthase for its cofactor, B6

Question 5

Methionine synthase deficiency is another cause of homocystinuria, but S-adenosylmethionine synthase deficiency is not.
Methionine synthase requires a vitamin B12 cofactor, so low B12 levels can lead to elevated homocysteine. However, vitamin B12 deficiency has a?

Answer 5

different clinical presentation than congenital homocystinuria.

Question 6

Mutations in the fibrillin gene are found in all patients with Marfan syndrome. Patients with Marfan syndrome appear similar to those with homocystinuria, but do not have increased risk of intellectual disability. Marfan syndrome is also associated with an upward lens dislocation, whereas the ocular lens in homocystinuria is characteristically dislocated downward.

Ehlers-Danlos syndrome (EDS) encompasses a group of disorders that are characterized by ?

Answer 6

defects in collagen synthesis or structure. EDS manifests with skin hyperextensibility, joint hypermobility, and tissue fragility.

Question 7

A chemotherapeutic agent is one used to disrupt the cell cycle such that the target cell population no longer grows. The agent used in this experiment arrests cells in prophase (disappearance of nuclear envelope and condensed chromatids). Prophase is followed by metaphase in which chromatids attach to spindle fibers via?

Answer 7

centromeres and are moved within the cell. For a cell to arrest in prophase, the functional cell components of metaphase (eg, centromeres) must be inhibited.

Question 8

The spindle apparatus is a complex structure that is essential for mitosis and meiosis. It involves microtubule polymerization at opposing centrosomes and microtubule capture by?

Answer 8

kinetochores located on each chromosome’s centromere. Therefore a drug that inhibits the function of the microtubules, kinesins, kinetochores, or centromeres would severely impair the assembly of the spindle apparatus and force the cells to arrest in prophase.

Question 9

Actin is a protein used in muscle contraction and organelle transport.
The microfilament is made of actin and is involved in cell and organelle movement.
p53 is a tumor suppressor protein that inhibits ?

Answer 9

cell cycle progression past the G1 phase.

Topoisomerase is a protein that “unwinds” DNA for replication during the S phase.

Question 10

This patient with worsening shortness of breath, a chronic cough, and a significant tobacco history is suffering from chronic obstructive pulmonary disease (COPD). Further physical examination would probably show signs of hyperinflation (barrel chest), decreased breath sounds, and characteristic pursing of the lips when breathing. Arterial blood gas analysis reveals mild hypoxemia and hypercapnia, which can develop in severe cases of COPD. The excess carbon dioxide in this patient’s lungs and blood is caused by the ineffective expirations and air trapping due to his COPD. Carbon dioxide is a substrate for?

Answer 10

carbonic anhydrase, the enzyme in RBCs that catalyzes its conversion to bicarbonate.

Question 11

Cyclin dependent kinases are molecules involved in cell cycle regulation and require cyclins for function. Na+/K+ ATPase and Na+/H+ exchanger are membrane proteins whose substrates appear in their names and are involved in metabolic regulation.
Nicotinamide adenosine dinucleotide phosphate (NAPDH) oxidase uses oxygen and NADPH as substrates to produce?

Answer 11

superoxide as a defence mechanisms against infectious organisms.

Question 12

Carbon dioxide is a substrate for carbonic anhydrase, the enzyme in red blood cells that catalyzes the conversion of carbon dioxide to bicarbonate. In COPD, impaired respiration leads to a build-up of this substrate in the lungs, causing?

Answer 12

chronic respiratory acidosis.

Question 13

This patient is most likely experiencing cyanide poisoning as evidenced by his confusion and headache following exposure to a house fire and successful treatment with nitrates and sodium thiosulfate. Cyanide poisoning impairs aerobic metabolism, causing?

Answer 13

lactic acidosis.

Question 14

Other causes of high-anion-gap metabolic acidosis can be remembered using the mnemonic MUDPILES: ?

Answer 14

Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde, Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates.

Cyanide poisoning causes an anion-gap acidosis due to increased serum lactate.

Cyanide causes elevated venous oxygen saturation, because it inhibits the body’s ability to utilize oxygen.

Question 15

In cyanide poisoning, oxygen is unable to serve as the final electron acceptor in the electron transport chain. Thus, oxidative phosphorylation is shut down, which forces the cells to?

Answer 15

rely on anaerobic metabolism for generation of adenosine triphosphate.

Question 16

The five main causes of metabolic alkalosis are?

Answer 16

loss of hydrogen ions (usually by vomiting or renal loss);
bicarbonate retention (usually by the kidneys);
shift of hydrogen ions to the intracellular space (seen in hypokalemia);
alkalotic agents such as bicarbonate or antacids;
and contraction alkalosis (water lost as a diuretic while bicarbonate is retained).

Question 17

This patient is consuming carbohydrate in excess of what is needed for her immediate energy needs. There are two fates of carbohydrate in this situation, glycogen and fatty acid. Fatty acid synthesis is stimulated by a building up of citrate. The cycle shown is the TCA, or Krebs, cycle. Citrate (label B), formed from oxaloacetate and acetyl coenzyme A (acetyl-CoA) by the enzyme citrate synthase, inhibits?

Answer 17

phosphofructokinase and allosterically activates acetyl-CoA carboxylase. Citrate is a key intermediate in the TCA cycle that inhibits phosphofructokinase. Additionally, citrate also activates acetyl-CoA carboxylase, thus driving fatty acid synthesis.

Question 18

Citrate is a key intermediate in the TCA cycle that inhibits phosphofructokinase. Citrate also activates acetyl-CoA carboxylase, thus driving?

Answer 18

fatty acid synthesis.

Question 19

This patient’s niece has a genetic disease that causes respiratory infections and pancreatic failure, which describes ?

Answer 19

cystic fibrosis. The patient wants to assess her chances of having a child with the disease. Cystic fibrosis is caused by a mutation in the CFTR gene. Polymerase chain reaction (PCR) and sequencing can be used to determine if this woman and/or her husband is a carrier of the cystic fibrosis gene. It’s the most common single gene mutation in the white population.

Question 20

Enzyme-linked immunosorbent assay (ELISA) involves the use of antibodies to identify the presence of a particular antigen or antibody.

Gel electrophoresis involves use of an electric field to separate ?

Answer 20

molecules by size, but would not be able to detect DNA mutations.

Northern blot is a test to identify specific fragments of RNA and gives information about gene transcription.

Question 21

A Southwestern blot involves a biochemical technique to identify specific DNA-binding proteins, but would not be helpful in DNA identification.

A karyotype analysis is helpful in identifying many genetic diseases caused by?

Answer 21

large chromosomal abnormalities, but a change in a few nucleotides (as is the case with CF) would not be detected.

Question 22

The new virus discovered by the researchers increases gut motility, thereby causing a decrease in gut transit time, limiting time for absorption, and eventually leading to diarrhea. The laboratory findings suggest that the virus does this by interfering with the signalling cascade controlling contraction of the gut smooth muscle.
When an action potential arrives at a smooth muscle cell (see image), the membrane depolarizes and voltage-gated calcium channels open. Calcium enters the cell and binds to calmodulin. This calcium-calmodulin complex activates myosin light-chain kinase (MLCK), which in turn?

Answer 22

phosphorylates myosin light chains (MLCs). Once phosphorylated, MLCs facilitate cross-bridge formation and smooth muscle contraction.

Question 23

The signaling cascade that leads to smooth muscle contraction starts with influx of Ca2+ from extracellular fluid, followed by binding of Ca2+ to calmodulin (CaM), which forms a complex that then activates ?

Answer 23

myosin light-chain kinase (MLCK). MLCK phosphorylates the myosin light chains, which triggers the formation of the cross bridge and subsequent contraction.

Question 24

This patient’s fatigue and pallor, along with a low hematocrit, suggest anemia. Lab findings of pancytopenia in conjunction with the skeletal abnormalities on exam suggest Fanconi anemia.
Fanconi anemia is an autosomal recessive disorder in which cells cannot properly repair a type of DNA damage known as interstrand cross-links. More than 85% of cases are diagnosed between the ages 4 and 15 years. Patients commonly present with thrombocytopenia or leukopenia, which gradually progresses to pancytopenia and eventually to ?

Answer 24

bone marrow failure. Bone marrow biopsy shows fatty infiltration. This patient’s nosebleeds are secondary to pancytopenia caused by progressive marrow failure. Two-thirds of patients with Fanconi anemia show some form of congenital abnormality, especially thumb abnormalities, hypogonadism, and microcephaly.

Patients with Fanconi anemia can be treated with corticosteroids or growth factors in the short term, but bone marrow transplant is needed to address the pancytopenia and its sequelae.

Question 25

Dietary modification is effective in treating inborn errors of metabolism, such as phenylketonuria and galactosemia. Folate supplementation and vitamin B12 supplementation are both used to treat ?

Answer 25

macrocytic anemia, which is characterized by an MCV > 100 fL. Although the RBC disorder in Fanconi anemia is often macrocytic, neither supplementation would address this patient’s underlying marrow failure. Vitamin C supplementation is used to treat scurvy, which arises from impaired collagen synthesis due to vitamin C deficiency.

Question 26

This patient has been in the hospital for 3 weeks, receiving treatment with cefotaxime for Klebsiella pneumonia. She develops a UTI caused by Enterococcus faecium, but vancomycin treatment is not successful. Vancomycin is a glycopeptide antibiotic that is effective in fighting only gram-positive bacteria, such as E. faecium. It binds tightly to a cell wall precursor that contains the terminal amino acid sequence D-ala D-ala and prevents ?

Answer 26

cell wall synthesis. An alteration to terminal amino acid of E. faecium’s cell wall component can lead to resistance.Resistance to vancomycin is transferred via plasmids and encodes enzymes that convert the D-ala D-ala peptide bridge to D-ala D-lac, preventing vancomycin from binding. Vancomycin resistance is much more common with Enterococcus faecium than with Enterococcus faecalis.

Question 27

Alterations in DNA gyrase are a mechanism for fluoroquinolone resistance. Vancomycin does not target DNA gyrase, therefore alterations in the gyrase enzyme would likely not influence the efficacy of vancomycin. Methylation of rRNA at a ribosome binding is a mechanism for macrolide resistance. rRNA methylation would likely not influence the ability of?

Answer 27

vancomycin to bind to bacterial cell wall components. Production of ß-lactamases and alterations in penicillin-binding proteins result in resistance to ß-lactams, however, vancomycin is not a ß-lactam.

Question 28

This patient presents to the emergency department with drowsiness, unsteady gait, enlarged liver, and nystagmus, suggesting he is most likely an?

Answer 28

intoxicated alcoholic. Thiamine deficiency is commonly seen in association with chronic alcoholism secondary to dietary insufficiency or impaired intestinal absorption. Thiamine deficiency can manifest in the form of Wernicke encephalopathy, which manifests with ataxia, oculomotor dysfunction, and encephalopathy; or Korsakoff psychosis, which results in anterograde and retrograde amnesia, often with confabulation.

Question 29

The other abnormalities are not associated with a thiamine deficiency. Elevated AST:ALT with a 1:1 ratio can be caused by several conditions, including viral hepatitis, but not thiamine deficiency; high urine metanephrines are found in?

Answer 29

pheochromocytoma; high urine protein is found in nephrotic syndrome; and thrombocytopenia is associated with folate deficiency.

Question 30

The patient’s lipid profile, including elevated LDL and triglyceride levels, is diagnostic of hyperlipidemia. Statins are the gold standard for treatment of hyperlipidemia when a patient can tolerate their side effects. They have been proven to decrease morbidity and mortality rates associated with atherosclerosis. Statins competitively inhibit?

Answer 30

hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol synthesis, by obstructing part of the enzyme's active site. The subsequent decrease in intrahepatic cholesterol causes upregulation of hepatic LDL cholesterol receptors, ultimately lowering plasma LDL cholesterol levels. The Michaelis-Menten constant (Km) is the concentration of a substrate that brings about an initial velocity that is half the maximum velocity (Vmax) of the reaction. Because statins bind to the same binding site as the substrates of the enzyme, statins increase HMG-CoA reductase's apparent Km. Well-known adverse effects of statin use include myalgia, myositis, and rhabdomyolysis.

Question 31

Statins have no effect on the maximum velocity (Vmax) of the reaction because they reversibly bind to the same site as HMG-CoA and can be outcompeted in the presence of very high concentrations of HMG-CoA. As for LDL, statins do not directly affect hepatic LDL receptor affinity for cholesterol (KD) or its activity. They indirectly increase the concentration of ?

Answer 31

hepatic LDL receptors on the surface of hepatocytes, so they increase (not decrease) the Vmax of the reaction between LDL receptors and LDL cholesterol.