Question 1

Acetyl-CoA enhances the rate of gluconeogenesis by acting as an obligate activator of which of the following enzymes?&#10;A) phosphoenolpyruvate carboxykinase&#10;B) phosphoglycerate kinase&#10;C) phosphoglycerate mutase&#10;D) pyruvate carboxylase&#10;E) pyruvate kinase

Accepted Answer

Acetyl-CoA is an allosteric activator of pyruvate carboxylase, which is a key enzyme in gluconeogenesis, converting pyruvate to oxaloacetate.  Unlike allosteric enzymes that function at some level in the absence on an allosteric effector, pyruvate carboxylase (PC) has no activity in the absence of acetyl-CoA. This property defines acetyl-CoA as an obligate activator of PC.

Question 2

The purpose of the Cori cycle is to shift the metabolic burden in which of the following directions?&#10;A) brain to liver&#10;B) cardiac to skeletal muscle&#10;C) liver to brain&#10;D) liver to muscle&#10;E) muscle to liver

Accepted Answer

The Cori cycle shifts the metabolic burden from muscle to liver by converting lactate produced in muscles during anaerobic glycolysis into glucose in the liver.  The Cori cycle represents a link between metabolic processes that occur in skeletal muscle and erythrocytes with those occurring in the liver. During anaerobic glycolysis in muscle the pyruvate is reduced to lactate. This pathway functions exclusively within erythrocytes because they lack mitochondria necessary for oxidation of NADH to NAD+. The lactate leaves these tissues, enters the blood, and is transported to the liver. Within the liver the lactate is oxidized to pyruvate and the pyruvate then serves as a substrate for glucose synthesis. The glucose leaves the liver and can be used by muscle and erythrocytes again.

Question 3

The maximum capacity of the liver to carry out gluconeogenesis during starvation depends upon which of the following?&#10;A) activation of glucose 6-phosphatase by insulin&#10;B) activation of pyruvate kinase by insulin&#10;C) induction of PEP carboxykinase synthesis by glucagon&#10;D) inhibition of fructose 1,6-bisphosphatase by F1,6BP&#10;E) inhibition of glucokinase by AMP

Accepted Answer

During starvation, glucagon induces the synthesis of PEP carboxykinase, a key enzyme in gluconeogenesis, enhancing the liver's capacity to produce glucose.  When blood glucose levels fall, the pancreas releases glucagon to stimulate the liver to carry out gluconeogenesis. The effects of glucagon exerted on hepatic metabolism are both short term and long term. Prolonged fasting and starvation lead to long-term glucagon effects which are exerted at the level of gene expression. A major hepatic target of these long-term effects is the transcription of the PEPCK gene which is induced by glucagon.

Question 4

A defect in lactate dehydrogenase would require the coupling of which enzyme reaction to that of glyceraldehyde-3-phosphate dehydrogenase in order for effective gluconeogenesis to proceed?&#10;A) glucose-6-phosphate dehydrogenase&#10;B) malate dehydrogenase&#10;C) PEP carboxykinase&#10;D) pyruvate carboxylase&#10;E) pyruvate dehydrogenase

Accepted Answer

Malate dehydrogenase is involved in the conversion of oxaloacetate to malate in the mitochondria and back to oxaloacetate in the cytosol, which is necessary for gluconeogenesis when lactate dehydrogenase is defective.  In order for gluconeogenesis to occur, the NADH needed by the reversal of the glycolytic glyceraldehyde-3-phosphate dehydrogenase reaction must be supplied by either lactate dehydrogenase or the action of cytosolic malate dehydrogenase. In the latter reaction, the enzyme participates in the malate-aspartate shuttle.

Question 5

You are studying a cell line in which gluconeogenesis is unaffected by changes in the level of acetylCoA. These cells most likely harbor an enzyme that has lost its allosteric binding site for acetyl-CoA. Which of the following enzymes is the candidate mutated-enzyme?

A) phosphoenolpyruvate carboxykinase
B) phosphoglycerate kinase
C) phosphoglycerate mutase
D) pyruvate carboxylase
E) pyruvate kinase

Accepted Answer

Pyruvate carboxylase is an enzyme in gluconeogenesis that is allosterically activated by acetyl-CoA. If gluconeogenesis is unaffected by acetyl-CoA levels, it suggests a mutation in pyruvate carboxylase affecting its allosteric site.  Pyruvate carboxylase activity is absolutely dependent on allosteric activation by acetyl-CoA. Therefore, this must be the affected enzyme in these cells

Question 6

You are analyzing the activity of cells in culture following the introduction of a mutant form of lactate dehydrogenase exhibiting only 20% of normal activity. These cells continue to exhibit a deficit in gluconeogenesis when pyruvate instead of lactate is added as a substrate. Analysis of the NAD+:NADH ratio indicates that it is elevated compared to normal cells. A defect in which of the following enzymes likely explains the observed results in these test cells?

A) glucose-6-phosphate dehydrogenase
B) malate dehydrogenase
C) PEP carboxykinase
D) pyruvate carboxylase
E) pyruvate dehydrogenase

Accepted Answer

In order for gluconeogenesis to occur, the NADH needed by the reversal of the glycolytic glyceraldehyde-3-phosphate dehydrogenase reaction must be supplied by either lactate dehydrogenase or the action of cytosolic malate dehydrogenase. Since there is a deficit in the reduction of NAD₊ to NADH, the additional defective enzyme must be cytosolic malate dehydrogenase.

Question 7

The ability of the liver to regulate the level of blood glucose is critical for survival. A number of sources of carbon atoms of nonhepatic origin are used by the liver for gluconeogenesis. However, the net conversion of carbons from fat into carbons of glucose cannot occur in humans because of which of the following?

A) oxidation occurs in the mitochondria and gluconeogenesis occurs in the cytosol
B) states of catabolism and anabolism are never concurrently active
C) storage of fats occurs in adipose tissue and gluconeogenesis occurs in liver and kidney
D) the carbons of acetyl-CoA from fat oxidation are lost as CO₂ in the TCA cycle
E) the carbons of acetyl-CoA from fat oxidation inhibit conversion of pyruvate to oxaloacetate

Accepted Answer

The carbons from acetyl-CoA, derived from fat oxidation, are released as CO2 in the TCA cycle, preventing their conversion into glucose.

Question 8

Shortly after birth, an infant presents with severe lactic acidemia, hyperammonemia, citrullinemia, and hyperlysinemia with the presence of α-ketoglurate in the urine. Definitive diagnoses of the causes of severe lactic acidemia are difficult and although these symptoms overlap with those seen with some of the urea cycle defect diseases, this is not the case with this neonate. A defect in which of the following enzymes would be expected to present with these findings?

A) acetyl-CoA carboxylase
B) electron transfer flavoproteinubiquinone oxidoreductase (EFT-QO)
C) glutamic acid decarboxylase (GAD)
D) phosphorylase
E) pyruvate carboxylase

Accepted Answer

Pyruvate carboxylase is the first enzyme in the gluconeogenic conversion of pyruvate carbons into glucose. A defect in pyruvate carboxylase would restrict the conversion of lactate into pyruvate and then subsequently to glucose. This would lead to severe lactic academia. The other symptoms are primarily the result of liver damage due to impaired gluconeogenesis.

Question 9

During early fasting, glycogen is used as a source of glucose for the blood. After liver glycogen is depleted which of the following occurs?&#10;A) amino acids of muscle proteins are used to synthesize glucose in the liver&#10;B) blood glucose falls below 5mM until carbohydrate is eaten&#10;C) fatty acids of adipose tissue are converted into glucose in the liver&#10;D) liver fatty acids are degraded as precursors for blood glucose&#10;E) muscle glycogen is used as a source of glucose for the blood

Accepted Answer

After liver glycogen is depleted, the body begins gluconeogenesis, where amino acids from muscle proteins are used to synthesize glucose in the liver to maintain blood glucose levels.  During periods of fasting and starvation, when liver glycogen levels are depleted, the major source of carbon atom for hepatic gluconeogenesis is from the amino acids released due to protein degradation within skeletal muscle.

Question 10

When pyruvate is the substrate for gluconeogenesis, which of the following is the fate of oxaloacetate prior to traversing the mitochondrial membrane?&#10;A) conversion to phosphoenolpyruvate&#10;B) oxidation to malate&#10;C) reduction to malate&#10;D) transamination to aspartate&#10;E) transamination to glutamate

Accepted Answer

Oxaloacetate is reduced to malate in the mitochondria to be transported across the mitochondrial membrane, as there is no direct transporter for oxaloacetate. Once in the cytosol, malate is oxidized back to oxaloacetate for gluconeogenesis. The inner mitochondrial membrane is impermeable to oxaloacetate (OAA). In order for the carbon atoms of OAA to be transported out into the cytosol, where they can serve as precursors for glucose synthesis, OAA is reduced to malate. The malate is transported across the inner mitochondrial membrane where in the cytosol is oxidized to OAA.

Question 11

Which of the following compounds would be utilized by a person on a carbohydrate-free diet as a source of carbon atoms for de novo glucose synthesis?&#10;A) palmitate&#10;B) b-hydroxybutyrate&#10;C) glycerol&#10;D) cholesterol&#10;E) acetoacetate

Accepted Answer

The answer of Which of the following compounds would be...

Question 12

Deficiencies in the enzyme glucose 6-phosphatase are likely to lead to which of the following?&#10;A) decreased glucagon production&#10;B) decreased skeletal muscle glycogen accumulation&#10;C) hyperglycemia&#10;D) increased hepatic glycogen accumulation&#10;E) increased accumulation of unbranched glycogen

Accepted Answer

The answer of Deficiencies in the enzyme glucose 6-phosphatase are...

Question 13

A 44-year-old man is brought to the emergency room after he was rescued from being trapped under rubble in a building collapse for 4 days. Blood work shows that his serum glucose concentration is within the reference range. Which of the following processes is the most likely explanation for the maintenance of a normal serum glucose concentration in this patient?

A) decreased ketone body formation
B) gluconeogenesis
C) hepatic glycogen breakdown
D) increased hepatic glycogen storage
E) protein synthesis

Accepted Answer

The answer of A 44-year-old man is brought to the...

Question 14

Plasma urea concentration is frequently up to 5-fold greater after a 5-day fast than after following a normal diet. This increase in urea concentration most likely reflects an increase in which of the following?

A) activity of carbamoyl phosphate synthetase I(CPS I)
B) rates of synthesis of ketone bodies
C) rates of transport of amino acids into skeletal muscle
D) rates of transport of fatty acids into skeletal muscle
E) use of amino acids for hepatic gluconeogenesis

Accepted Answer

The answer of Plasma urea concentration is frequently up to...

Question 15

A normal subject fasts overnight. In the morning serum glucose concentrations are within the reference range. Which of the following is the best explanation for this result?&#10;A) hepatic gluconeogenesis in response to insulin&#10;B) hepatic gluconeogenesis in response to glucagon&#10;C) hepatic ketogenesis in response to glucagon&#10;D) muscle glycogenolysis in response to glucagon&#10;E) muscle ketogenesis in response to insulin

Accepted Answer

The answer of A normal subject fasts overnight. In the...

Question 16

A 2-year-old boy with weakness on exertion is found to have a pyruvate carboxylase deficiency. Which of the following compounds could this child use as a substrate for gluconeogenesis?&#10;A) alanine&#10;B) glycerol&#10;C) lactate&#10;D) proline&#10;E) pyruvate

Accepted Answer

The answer of A 2-year-old boy with weakness on exertion...

Question 17

An obese 25-year-old woman starts following an extreme low-carbohydrate, high-fat diet. Which of the following components or immediate metabolites of her new diet can be used to help maintain adequate serum glucose concentration?

A) acetoacetate
B) cholesterol
C) glycerol
D) hydroxybutyrate
E) palmitate

Accepted Answer

The answer of An obese 25-year-old woman starts following an...

Question 18

Although fructose-1,6-bisphosphatase (F1,6BPase) deficiency can lead to infant mortality due to severely impaired gluconeogenesis, beyond childhood afflicted individuals develop hypoglycemia usually only associated with fasting or febrile infections. Given the role of F1,6BPase in overall carbohydrate metabolism, which of the following metabolites would be expected to increase in the plasma of these patients following depletion of hepatic glycogen stores?

A) acetyl-CoA
B) cholesterol
C) free fatty acids
D) lactate
E) pyruvate

Accepted Answer

The answer of Although fructose-1,6-bisphosphatase (F1,6BPase) deficiency can lead to...

Deck 13: Carbohydrates: Gluconeogenesis, the Synthesis of New Glucose