Review Flashcards
A woman with a mitochondrial disorder was given supplements of riboflavin and Coenzyme Q. Which ONE of the following describing the role of CoQ in the respiratory
chain is NOT correct?
A. It mediates electron transport between complex I and cytochrome b-c1.
B. It mediates electron transport between complex II and cytochrome b-c1.
C. It is reduced by glycerol 3-phosphate dehydrogenase in the glycerol 3- phosphate
shuttle, which allows NADH obtained from glycolysis to be used to make ATP.
D. It mediates electron transport between complex IV and oxygen.
E. It is the only lipid soluble molecule in the respiratory chain.
D. Feedback: CoQ is the only lipid soluble component in the electron transport chain, and it oxidizes complex I and reduces cyt b in complex III, and can also oxidize complex II and reduce cyt b in complex III. It also plays a role in the glycerol 3-phosphate shuttle, getting reduced by the inner membrane FAD containing complex glycerol 3-phosphate dehydrogenase. However, it does NOT mediate transport between complex IV and oxygen.
A comatose laboratory technician is rushed into the emergency room. You later learn that her lab has been working on cyanide as a metabolic inhibitor and that there is a high likelihood that she ingested, by accident, an extremely high dose of cyanide. What would be the best immediate response?
A. Give her an oral dose of atractyloside
B. Administer high concentrations of rotenone
C. Administer an oxidizing agent
D. Administer a reducing agent
E. Administer Coenzyme Q
Correct answer: C. Feedback: The treatment for cyanide poisoning involves first inhalation then injection of an oxidizing agent to convert Hb to metHb (oxidized form), which has a high affinity for cyanide. The MetHb will quickly remove any CN from the blood, so that it will not bind to cytochrome oxidase in the electron transport chain and inhibit ATP formation.
Which ONE of the following statements concerning the cytochromes in the electron transport chain is CORRECT?
A. Cytochromes contain iron-‑sulfur centers as electron transfer prosthetic groups.
B. Only the cytochrome moieties in complex IV of the electron transport chain can bind oxygen.
C. Each complex in the electron transport chain contains at least one cytochrome.
D. All cytochromes are part of complexes of the inner mitochondrial membrane.
Correct answer: B. Feedback: B is the correct statement, since only cytochrome a3 (part of cytochrome c oxidase, complex IV) can bind oxygen, while all the other cytochromes do not bind oxygen.
A 25-year-old woman with Kearns-Sayre syndrome (KSS) had complete external ophthalmoplegia, short stature, ataxia, cardiac conduction defects, and pigmentary retinopathy. Muscle biopsy revealed ragged-red fibers. Electron microscopy showed increased numbers of mitochondria with disordered structure and paracrystalline inclusions. Enzymatic analysis revealed a deficiency of complex II of the mitochondrial respiratory chain. Which of the molecule would not be oxidized due to the impaired electron transport?
A. Citrate
B. Glycerol-3-phosphate
C. Pyruvate
D. Succinate
E. Malate
Correct answer: D. Feedback: Complex II is also known as succinate dehydrogenase, an enzyme within the TCA cycle. It is embedded in the inner mitochondrial membrane facing the matrix. In this complex succinate is oxidized to fumarate while FAD is reduced to FADH2. Complex II transfers 2 electrons from FADH2 to CoQ. Glycerol-3-phosphate dehydrogenase behaves just like Complex II, but it is embedded in the inner mitochondrial membrane facing the intermembrane space. Citrate, pyruvate and malate do not participate in electron transport chain.
Which one of the following statements concerning the components and the process of oxidative phosphorylation is INCORRECT?
A. An uncoupler protein facilitates the transport of protons across the inner mitochondrial membrane.
B. Cyanide is toxic because it inhibits the activity of cytochrome c oxidase.
C. Cytochrome c is the only water soluble component of the electron transport chain.
D. Atractyloside is a lethal compound because it uncouples the process of oxidative phosphorylation.
E. Oligomycin is an inhibitor of the proton channel of the ATP synthase.
Correct answer: D. Feedback: Atractyloside is lethal because it is an inhibitor of the adenine nucleotide carrier (ANC, ANT).
Which ONE of the following statements regarding glycolysis is CORRECT?
A. Elevated levels of NADH promote the conversion of pyruvate to lactate.
B. At the cellular level, the conversion of glucose to pyruvate is promoted by high levels of citrate.
C. The principal rate-limiting step in glycolysis is a reversible reaction.
D. In the period of time during and immediately following ingestion of a glucose-rich meal, glucokinase is less contributory than is hexokinase to glucose metabolism in the liver.
E. The conversion of fructose 6-phosphate to fructose 1,6-bisphosphate is an example of substrate level phosphorylation.
Correct answer: A. Feedback: NADH is a cofactor in the reduction of pyruvate to lactate (that occurs under anaerobic conditions). If NADH levels rise in the cell, they must be ‘recycled’ to NAD+ by some means for glycolysis to continue. Absent an adequate oxygen supply to do this via oxidative phosphorylation, anaerobic glycolysis ensue. Glycolysis is inhibited in the presence of elevated citrate. The rate-limiting step of glycolysis (catalyzed by PFK-1) is a unidirectional reaction. Glucokinase has a higher Vmax and Km for glucose that does hexokinase. The conversion of fructose 6-phosphate to fructose 1,6bisphoaphate consumes an ATP molecule rather than producing one, and does not create a high- energy phosphate bond so it is not an example of substrate level phosphorylation.
Phosphorylation and dephosphorylation of selected proteins involved in metabolism plays a major role in regulating the flux of metabolites through any given pathway. Which ONE of the following statements in that regard CORRECTLY describes an example of
this in liver?
A. Dephosphorylation of the bifunctional enzyme, PFK-2/FBP-2, results directly or indirectly in increased synthesis of both fructose 1,6-bisphosphate and fructose 2,6- bisphosphate.
B. Dephosphorylation of PFK-1 leads to a significant increase in its activity.
C. Phosphorylation of the bifunctional enzyme, PFK-2/FBP-2, leads to increased synthesis of fructose 1,6 bisphosphate.
D. Dephosphorylation of pyruvate kinase is the result of glucagon signaling.
E. Phosphorylation of the Glut-4 transporter alters its Km for glucose.
Correct answer: A. Feedback: PFK- 2/FBP-2 in its dephosphorylated state synthesizes fructose 2,6-bisphosphate, which in turn is an allosteric activator of PFK-1. There is no direct phosphorylation event on PFK-1.
Phosphorylation of the bifunctional enzyme decreases fructose 1,6- bisphosphate synthesis. Glucagon signaling leads to phosphorylation of pyruvate kinase. Lastly, there is no phosphorylation event on the Glut-4 transporter.
Which statement below correctly describes glucokinase?
A. It is widely distributed and occurs in most human tissue types.
B. It has a high Km for glucose and, hence, is important in the phosphorylation of glucose primarily after ingestion of a carbohydrate-rich meal.
C. It is inhibited by glucose 6-phosphate.
D. It performs the first substrate level phosphorylation in the glycolytic pathway.
Correct answer: B. Feedback: Glucokinase is found primarily in the liver and pancreas, while its isozyme partner hexokinase is widely distributed among human tissues. Glucokinase is not inhibited by glucose6-phosphate, while hexokinase is. The phosphorylation of glucose to glucose 6-phosphate is not an example of substrate
level of phosphorylation.
One of your patients recently underwent splenectomy due to an autosomal recessive glycolytic enzyme deficiency that caused hemolytic anemia. Which of the following is a common clinical sign in neonatal presentation of this disorder?
A. Sepsis
B. Jaundice
C. Hepatomegaly
D. Seizures
Correct answer: B. Feedback: Pyruvate kinase deficiency causes a congenital nonspherocytic hemolytic anemia with resultant hyperbilirubinemia. The breakdown may be so severe as to put the neonate at risk for bilirubin encephalopathy and require exchange transfusion. Blood transfusion may be indicated for the anemia. Splenectomy improves the anemia but does not cure the underlying defect.
Which ONE of the following statements regarding the digestion and absorption of dietary lipids is CORRECT?
A. Lipoprotein lipase is found mainly in the duodenum.
B. Pancreatic lipase removes fatty acids from carbons 1 and 3 of the triacylglycerol.
C. Unless packaged in mixed micelles, medium and short chain fatty acids will not be absorbed in the intestine.
D. Hormone sensitive lipase is activated by cholecystokinin.
E. The fatty acids present on dietary phospholipids are not efficiently absorbed by the intestine.
Correct answer is B. Lipoprotein lipase is is an extracellular enzyme on the vascular endothelial surface that degrades triglycerides in lipoprotein particles (VLDL and chylomicrons) in the bloodstream. Medium and short chain fatty acids are sufficiently soluble in the serum that they are passed into the portal circulation and carried to the liver. Hormone sensitive lipase is stimulated by epinephrine and glucagon in adipocytes. Given the presence of active phospholipase, the fatty acids that are attached to dietary phospholipids are efficiently cleaved from the parent compound and absorbed by the intestine for rejoining to form fatty esters, with packaging into chylomicrons
Complete the following sentence so that it is CORRECT: “Linoleic and linolenic acids must be supplied in the diet because…”
A. humans are unable to synthesize fatty acids longer than 16 carbons in length.
B. they negatively regulate cholesterol biosynthesis in the liver.
C. they are selectively degraded by enzymes in the small intestine.
D. humans are unable to introduce double bonds in fatty acids at anyposition.
E. humans are unable to introduce double bonds in fatty acids past α-carbon #9.
Correct answer is E.
Complete the following sentence so that is CORRECT: “The enzyme that regulates the synthesis of fatty acids….”
A. is located in the mitochondrial matrix.
B. is “feed forward” activated by the products of the reaction it catalyzes.
C. is also involved in the synthesis of the ketone bodies.
D. is expressed at different levels depending upon the composition of the diet.
Correct answer is D. Feedback: The enzyme, acetyl CoA carboxylase, is located in the cytoplasm. Acetyl CoA carboxylase is inhibited by its product, malonyl CoA.
Diets high in carbohydrate or low in fat will lead to increased expression of acetyl CoA carboxylase, in a mechanism mediated by insulin acting as a transcriptional regulator.
Which ONE of the following statements regarding beta-oxidation of saturated and unsaturated fatty acids is CORRECT?
A. Different sets of dehydrogenase enzymes are required for the beta-oxidation of saturated and unsaturated fatty acids.
B. Unsaturated fatty acids must be saturated prior to their becoming substrates for beta- oxidation.
C. The presence of a double bond in a fatty acid means that its beta-oxidation will yield more chemical energy than does the beta-oxidation of a saturated fatty
acid of equal carbon content.
D. Isomerization of double bonds may be required before complete beta- oxidation of an unsaturated fatty acid can be carried out.
E. Methylmalonyl CoA is an intermediate in the beta-oxidation of fatty acids with unsaturated double bonds.
Correct answer is D. Feedback: The same dehydrogenases are used for saturated and unsaturated fatty acids; but what is also required for some unsaturated fatty acids is an isomerization to relocate the double bond(s) so that they are ‘in frame’ with the enzyme of beta- oxidation that that adds a water to that double bond (enoyl CoA hydratase).
Unsaturated fatty acids will yield less chemical energy than will a saturated fatty acid because they are LESS reduced than a saturated fatty acid.
Oxidation of fatty acids with an odd number of carbon atoms leads to the production of which ONE of the following common metabolic intermediates?
A. Palmitate
B. Malonate
C. Alpha-ketoglutarate
D. Acetoacetyl CoA
E. Succinyl CoA
Correct answer is E. Feedback: The three carbon propionyl CoA is carboxylated to methylmalonyl CoA, which is then converted by a vitamin B12-dependent mutase to succinyl CoA. The CoA group is removed and succinate can join the pool of TCA intermediates
All of the following are true statements regarding ketone bodies EXCEPT which ONE?
A. The ketone bodies include acetoacetate and beta-hydroxybutyrate.
B. They are water soluble compounds from which metabolic energy can be obtained.
C. They are synthesized in the liver from acetyl CoA and malonyl CoA.
D. They are utilized by the brain during starvation, helping to conserve glucose.
E. They are often present in the blood at high levels in uncontrolled diabetes mellitus.
Correct answer is C. Feedback: Liver is able to synthesize the ketone bodies starting with only acetyl CoA, but does not use malonyl CoA. Malonyl Coa plays no part in ketone body synthesis, though it is an essential intermediate in fatty acid production.
In skeletal muscle, increased hydrolysis of ATP during muscular contraction leads to which of the following?
A. A decrease in the rate of palmitate oxidation to acetyl CoA
B. A decrease in the rate of NADH oxidation by the electron-transport chain
C. Activation of PFK-1
D. An increase in the proton gradient across the inner mitochondrial membrane
E. Activation of glycogen synthase
Correct answer is C. Feedback: A decrease in the concentration of ATP (which occurs as muscle contracts) stimulates processes that generate ATP.
The proton gradient across the inner mitochondrial membrane decreases as protons enter the matrix via the ATPase in order to synthesize ATP;
The major role of acetyl-CoA carboxylase 2 in muscle is which of the following?
A. To regulate the level of fatty acid oxidation.
B. To allow for NADPH generation in the sarcoplasm.
C. To generate malonyl CoA for the synthesis of fatty acids.
D. To produce malonyl CoA for purine synthesis
E. To regulate the level of glycolysis
Correct answer is A. Feedback: Acetyl CoA carboxylase produces malonyl CoA, which inhibits carnitine palmitoyl transferase I, one of the enzymes required to transport fatty acids into the mitochondria to be oxidized.
The muscle does not synthesize fatty acids, nor is malonyl Co A used for purine synthesis. Acetyl CoA carboxylase requires biotin and ATP, and does not generate NADPH. Malonyl CoA is also not a regulator of glycolysis; its only regulatory role is that of fatty acid transport into the mitochondria
Which ONE of the following statements regarding galactose and its metabolism is CORRECT?
A. Galactose can only be converted to free glucose by way of its incorporation into glycogen.
B. While galactose itself does not appear to be toxic, galactitol and galactose 1- phosphate have toxic effects when present in cells at high concentrations.
C. Two different kinases are equally able to phosphorylate free galactose upon sugar entrance into the hepatocyte.
D. Classical galactosemia results from a deficiency of pancreatic lactase
Correct answer is B. Feedback: Galactose can be isomerized to glucose at the UDP-galactose stage of its metabolism, without the need to be incorporated into a glycogen polymer. Galactose 1-phosphate is the product of galactokinase activity. Classical galactosemia is the deficiency for the galactose 1-phosphate uridyltransferase.
Which ONE of the following statements about the digestion and absorption of dietary carbohydrates is CORRECT?
A. Digestion of some di- and tri-saccharides begins with enzymes present in the saliva.
B. In contrast to other digestive enzymes, salivary alpha-amylase remains active in the acidic environment of the stomach.
C. The pancreas secretes a number of di- and tri-saccharide hydrolases.
D. Lactose intolerance results from a deficiency of the enzyme beta- galactosidase.
E. Amylase is able to hydrolyze both the alpha 1-4 and alpha 1-6 bonds of glycogen and starch.
The correct answer is D. Feedback: Digestion of glycogen and starch begins in the mouth, with salivary alpha-amylase, but this enzyme is not active on di- and tri-saccharides. This enzyme is denatured in the low pH of the stomach. The pancreas secretes its own amylase, but the small intestine synthesizes the di- and tri-saccharide hydrolases. Amylase is only able to hydrolyze glycogen and starch at the alpha 1- 4 linkages.
Which ONE of the following statements about human disaccharidases is CORRECT?
A. The disaccharidases are produced and secreted by cells of the pancreas.
B. A specific intestinal disaccharidase cleaves alpha 1-4 glycosidic bonds in the human gut.
C. The monosaccharides produced by the disaccharidases are absorbed in the large intestine and pass into the portal circulation.
D. Due to redundancy of substrate specificity, a deficiency of any one specific disaccharidase has little effect on an individual’s ability to digest dietary carbohydrates.
correct choice is B. Feedback: The disaccharidases are synthesized in the brush border of the intestine. Humans do not have an enzyme that can hydrolize the beta 1,4 glycosidic bond. The monosaccharides that result from digestion of simple and complex sugars in the diet are normally absorbed in the small intestine. Each disaccharidease has well defined substrate specificity and these specificities are non-overlapping, such that deficiency for any one of them can lead to significant loss of ability to digest dietary carbohydrate
explain why glucose-6-phosphate dehydrogenase deficiency presents with increased accumulation of lipid oxidation products
glucose-6-phosphate dehydrogenase is committed step of HMP (aka PPP) pathway, which produces NADPH for biosynthesis of fatty acids, etc
if NADPH can’t be produced, then it makes sense that products of beta oxidation (breakdown) will accumulate
Glucose 6-phosphate dehydrogenase deficiency is associated with ALL of the following EXCEPT which ONE?
A. Crosslinking of hemoglobin tetramers in red blood cells
B. Shutdown of the non-oxidative phase of the hexose monophosphate pathway
C. Hemolytic anemia
D. Elevated sensitivity to certain drugs and dietary components
E. Depletion of reduced glutathione
Correct answer is B. Feedback: The non-oxidative phase of the pathway can proceed in the absence of glucose 6-phosphate dehydrogenase
Epinephrine-induced changes in glycolysis rates differ significantly when comparing liver and cardiac muscle. This can be explained, in part, by the observation that….
A. cardiac muscle does not express the glucagon receptor.
B. liver is unable to metabolize ketone bodies while cardiac muscle can use this energy source.
C. these two tissues have different isoenzymes of PFK-2/FKB-2
D. cardiac muscle has more mitochondria per cell than does liver.
E. cardiac muscle lacks glucose 6-phosphatase while liver does express this enzyme
Answer = C: Cardiac muscle is not a gluconeogenic organ. Epinephrine’s signal to cardiac muscle is to accelerate glycolysis, in the context of a flight or fright circumstance, while its signal to liver is to release glucose.
The bifunctional enzyme, PPFK-2/FBP-2 in each tissue responds differently to phosphorylation (the result of epinephrine signaling). Liver enzyme activates the FBP-2 enzyme while cardiac muscle further activates the PFK-2 activity
Fructose 2,6-bispohosphate is an important player in establishing the rate of glycolysis. In that regard, which ONE of the following statements is CORRECT?
A. In the brain, fructose 2,6-bisphosphate levels will increase as blood insulin levels increase.
B. Fructose 2,6-bisphosphate is an allosteric activator of two glycolytic enzymes in the liver: phosphofructokinase-1 and pyruvate kinase.
C. Fructose 2,6-bisphosphate is created by PFK-2 upon insulin signaling.
D. Fructose 2,6-bisphosphate is created by the isomerization of fructose 1,6- bisphosphate.
E. Phosphorylation of the bi-functional enzyme (PFK-2/FBP-2) leads to inhibition of the phosphatase and activation of the kinase.
Answer: C. Feedback: Fructose 2,6-bisphosphatase is created by PFK-2, and is an inhibitor of gluconeogenesis (promotes glycolysis)
F-2,6-BP is broken down by FBPase2
Brain is not responsive to insulin stimulation.
Activity of which ONE of the enzymes associated with glycogen metabolism is modulated by the degree of phosphorylation of the enzyme protein?
A. Phosphodiesterase
B. Glycogen synthase
C. Branching enzyme
D. Debranching enzyme, alpha-glucosyltransferase activity
E. Adenylate cyclase
B. Glycogen synthase - inactivated by phosphorylation
glycogen phosphorylase is also modulated by phosphorylation (activated)
Complete the following sentence so that it is CORRECT: Injection of glucagon into an individual in a well-fed state (3-5 hours after a meal)…..
A. will lead to a decreased level of fructose 2,6-bisphospahte in the muscle.
B. will lead to an increased level of fructose 2,6-bisphophate in the liver.
C. will result in stimulation of glycogen synthesis in all tissues.
D. will induce glycogenolysis in liver, but not in muscle
Answer: D. Feedback: Glucagon does not affect muscle. It will cause an elevation in glycemia
(glycogenolysis and gluconeogenesis) and consequently increased insulin secretion. Fructose 2,6-bisphosphate (pro-glycolysis) levels in the liver would decrease
as fatty acids are elongated, they are always attached to…
…fatty acid synthase enzyme
Laboratory results for a patient with uncontrolled Type I diabetes mellitus reveal hyperglycemia (634 mg/dL) and hypertriglyceridemia (498 mg/dL). The most likely cause of the hypertriglyceridemia in this patient is which of the following?
A. Deficiency in apoprotein C-II
B. Increased hepatic triglyceride synthesis
C. Decreased lipoprotein lipase activity
D. Deficiency in LDL receptors
E. Absence of hormone-sensitive lipase
Correct answer is C. Feedback: Decreased lipoprotein lipase activity is the result of the failure of the pancreatic β-cells to produce and secrete insulin. Insulin stimulates the synthesis of lipoprotein lipase; in the absence of insulin, lipoprotein lipase activity in the capillary beds is low.
Which ONE of the following is the MOST serious short-term clinical manifestation that
might occur in an untreated diabetic?
A. Vascular disease
B. Severe ketoacidosis
C. Hyperglycemia
D. Brain damage
Correct answer is B. Feedback: Diabetic ketoacidosis can be life threatening and must be treated immediately. Vascular disease is a long-term complication of diabetes. Hyperglycemia is undesirable because it promotes long–term complications. Brain damage is unlikely and in any event is not as immediate a concern as is ketoacidosis.
diagnosis is type II diabetes mellitus. A mutation, leading to decreased activity, in the gene encoding for which of these proteins is most consistent with this clinical presentation?
A. Glucagon
B. Glucose transporter isoform 1
C. Glycogen phosphorylase
D. Pyruvate carboxylase
E. Protein phosphatase 1
Correct answer is E. Feedback: The underlying cause of type II diabetes mellitus is insulin resistance (an inability to respond normally to physiological concentrations of insulin). Protein phosphatase 1 is an integral mediator of the metabolic effects of
insulin.
Which of the following complications is less likely to be associated with type II diabetes, as opposed to type I diabetes?
A. Retinopathy
B. Weight gain
C. Cardiovascular disease
D. Hypoglycemic coma
E. Neuropathy
Correct answer is D. Feedback: Hypoglycemia is a common complication associated with over supplementation of type I diabetics with insulin. This is less common in type II diabetics, because insulin therapy generally occurs only in the later stages of the pathogenesis of this disease.
Which ONE of the following is the most abundant precursor of blood glucose after one week of starvation?
A. Glycerol
B. Liver glycogen
C. Fructose
D. Acetyl CoA
Correct answer is A. Feedback: There is increased free fatty acids and glycerol concentrations during starvation due to accelerated breakdown of TAGs to provide energy to tissues and provide energy for the liver to do gluconeogenesis
Signaling pathways in the metabolism of glycogen and triacylglycerols have a number of similarities, and a few differences. In this regard, which ONE of the following statements is CORRECT?
A. Glycogen breakdown is controlled, in part, by intracellular cAMP levels, but cAMP plays no role in the mobilization of triacylglycerols.
B. Both glycogen breakdown and fatty acid oxidation occur in the cytoplasm.
C. In liver, the products of both glycogen breakdown and fatty acid oxidation are used as precursors for glucose synthesis.
D. In contrast to the case of glycogen stores in liver and muscle, there is no specific mechanism to limit triacylglycerol synthesis in liver or adipose while substrates are abundant
Correct answer is D. Feedback: While the size of glycogen stores in liver and muscle are regulated, dietary carbohydrate and fat in excess of immediate need is converted to triacylglycerol and stored in adipose depending only upon the dietary supply
