0.1. Which one of the following statements concerning gluconeogenesis is correct?
A. It is an energy-producing (exergonic) process.
B. It is important in maintaining blood glucose during a 2-day fast.
C. It is inhibited by a fall in the insulin/glucagon ratio.
D. It occurs in the cytosol of muscle cells.
E. It uses carbon skeletons provided by fatty acid degradation.
Correct answer = B. During a 2-day fast, glycogen stores are depleted, and gluconeogenesis maintains blood glucose. This is an energy-requiring (endergonic) pathway (both ATP and GTP get hydrolyzed) that occurs primarily in the liver, with the kidneys becoming major glucose producers in prolonged fasting. Gluconeogenesis uses both mitochondrial and cytosolic enzymes and is stimulated by a fall in the insulin/glucagon ratio. Fatty acid degradation yields acetyl coenzyme A (CoA), which cannot be converted to glucose. This is because there is no net gain of carbons from acetyl CoA in the tricarboxylic acid cycle, and the pyruvate dehydrogenase complex is physiologically irreversible. It is the carbon skeletons of most amino acids that are glucogenic.
0.2. Which reaction in the diagram below would be inhibited in the presence of large amounts of avidin, an egg white protein that binds and sequesters biotin?
Correct answer = C. Pyruvate is carboxylated to oxaloacetate by pyruvate carboxylase, a biotin-requiring enzyme. B (pyruvate dehydrogenase complex) requires thiamine pyrophosphate, lipoic acid, flavin and nicotinamide adenine dinucleotides (FAD and NAD+), and coenzyme A; D (transaminase) requires pyridoxal phosphate; E (lactate dehydrogenase) requires NADH.
0.3. Which one of the following reactions is unique to gluconeogenesis? A. 1,3-Bisphosphoglycerate → 3-phosphoglycerate
B. Lactate → pyruvate
C. Oxaloacetate → phosphoenolpyruvate
D. Phosphoenolpyruvate → pyruvate
Correct answer = C. The other reactions are common to both gluconeogenesis and glycolysis.
0.4. Use the chart below to show the effect of adenosine monophosphate (AMP) and fructose 2,6-bisphosphate on the listed enzymes of gluconeogenesis and glycolysis.
Both fructose 2,6-bisphosphate and adenosine monophosphate inhibit fructose 1,6-bisphosphatase of gluconeogenesis and activate phosphofructokinase-1 of glycolysis. This results in reciprocal regulation of the two pathways.
0.5. The metabolism of ethanol by alcohol dehydrogenase produces reduced nicotinamide adenine dinucleotide (NADH) from the oxidized (NAD+) form. What effect is the fall in the NAD+/NADH ratio expected to have on gluconeogenesis? Explain.
The increase in NADH as ethanol is oxidized decreases the availability of oxaloacetate (OAA) because the reversible oxidation of malate to OAA by malate dehydrogenase of the tricarboxylic acid cycle is driven in the reverse direction by NADH. Additionally, the reversible reduction of pyruvate to lactate by lactate dehydrogenase is driven to lactate by NADH. Thus, two important gluconeogenic substrates, OAA and pyruvate, decrease as a result of the increase in NADH during ethanol metabolism. Consequently, gluconeogenesis decreases.