Insulin promotes the uptake of glucose, while most enzymes regulated by covalent modification are in the phosphorylated state. Acetyl coenzyme A oxidation is increased, but the synthesis of glucokinase is repressed. The absorptive state, characterized by increased insulin and decreased glucagon levels, stimulates the synthesis of fructose 2,6-bisphosphate, which activates phosphofructokinase-1 of glycolysis. Covalently modified enzymes are typically dephosphorylated and active. In the well-fed state, acetyl coenzyme A is not oxidized as it is used in fatty acid synthesis. Glucose uptake into the liver is independent of insulin, and insulin induces the synthesis of glucokinase. 

In an individual fasting for 12 hours, hormone-sensitive lipase of adipocytes is phosphorylated and activated by protein kinase A in response to epinephrine. Arginase, carnitine palmitoyltransferase-I, fatty acid synthase, phosphofructokinase-1, glycogen synthase, and pyruvate dehydrogenase are either not regulated covalently or inactive when phosphorylated. 

During a four-week fast, ketone bodies, derived from the acetyl coenzyme A produced during fatty acid oxidation, become the major source of caloric needs for the brain. This typically occurs in the second to third week of fasting, as ketone bodies must reach a critical level to cross the blood-brain barrier. However, the fat stores in a 70-kg man would not be sufficient to meet his energy needs for five months. 

In the diagram representing inputs and outputs from pyruvate, the reaction requiring biotin and activated by acetyl coenzyme A is represented by the letter C. This reaction is performed by pyruvate carboxylase, an enzyme involved in gluconeogenesis. Pyruvate carboxylase, found in the mitochondria, requires biotin and ATP and is allosterically activated by acetyl coenzyme A from fatty acid oxidation. The other choices (A, B, D, E, and F) do not meet these criteria. 

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B. Insulin stimulates the uptake of glucose.
C. Most enzymes that are regulated by covalent modification are in the phosphorylated state.
D. The oxidation of acetyl coenzyme A is increased.
E. The synthesis of glucokinase is repressed.
Correct answer = A. The increased insulin and decreased glucagon levels characteristic of the absorptive state promote the synthesis of fructose 2,6bisphosphate, which allosterically activates phosphofructokinase-1 of glycolysis. Most covalently modified enzymes are in the dephosphorylated state and are active. Acetyl coenzyme A is not oxidized in the well-fed state because it is being used in fatty acid synthesis. Uptake of glucose (by glucose transporter-2) into the liver is insulin independent. Synthesis of glucokinase is induced by insulin in the well-fed state.
4.3. Which one of the following enzymes is phosphorylated and active in an individual who has been fasting for 12 hours?
A. Arginase
B. Carnitine palmitoyltransferase-I
C. Fatty acid synthase
D. Glycogen synthase
E. Hormone-sensitive lipase F. Phosphofructokinase-1
G. Pyruvate dehydrogenase
Correct answer = E. Hormone-sensitive lipase of adipocytes is phosphorylated and activated by protein kinase A in response to epinephrine. Choices A, B, C, and F are not regulated covalently. Choices D and G are regulated covalently but are inactive if phosphorylated.
4.4. For a 70-kg man, in which one of the periods listed below do ketone bodies supply the major portion of the caloric needs of brain?
A. Absorptive period
B. Overnight fast
C. Three-day fast
D. Four-week fast
E. Five-month fast
Correct answer = D. Ketone bodies, made from the acetyl coenzyme A product of fatty acid oxidation, increase in the blood in fasting but must reach a critical level to cross the blood–brain barrier. Typically, this occurs in the second to third week of a fast. Fat stores in a 70-kg (~154-lb) man would not be able to supply his energy needs for 5 months.
24.5. The diagram below shows inputs to and outputs from pyruvate, a central molecule in energy metabolism.
Which letter on the diagram represents a reaction that requires biotin and is activated by acetyl coenzyme A?
Correct answer = C. Pyruvate carboxylase, a mitochondrial enzyme of gluconeogenesis, requires biotin (and ATP) and is allosterically activated by acetyl coenzyme A from fatty acid oxidation. None of the other choices meets these criteria. A = pyruvate kinase; B = pyruvate dehydrogenase complex; D = aspartate aminotransferase; E = alanine aminotransferase; F = lactate dehydrogenase.
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I. OVERVIEW