Modulation of Acetyl-CoA Carboxylase Acetyl-CoA carboxylase is the principal regulation point in the biosynthesis of fatty acids. Some of the properties of the enzyme are described below.
(a) Addition of citrate or isocitrate raises the $V_{\max }$ of the enzyme as much as 10 -fold. (b) The enzyme exists in two interconvertible forms that differ markedly in their activities:

$$\text { Protomer (Inactive) } \rightleftharpoons \text { filamentouspolymer (active) }$$

Citrate and isocitrate bind preferentially to the filamentous form, and palmitoyl-CoA binds preferentially to the protomer.
Explain how these properties are consistent with the regulatory role of acetyl-CoA carboxylase in the biosynthesis of fatty acids.

Net Equation of Fatty Acid Synthesis Write the net equation for the biosynthesis of palmitate in rat liver, starting from mitochondrial acetyl-CoA and cytosolic NADPH, ATP, and $\mathrm{CO}_2$.

Synthesis of Fatty Acids from Glucose After a person has ingested large amounts of sucrose, the glucose, and fructose that exceed caloric requirements are transformed into fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How are these substances produced from glucose?

Potential Side Effects of Treatment with Statins Although clinical trials have not yet been carried out to document benefits or side effects, some physicians have suggested that patients being treated with statins also take a supplement of coenzyme $Q$. Suggest a rationale for this recommendation.

Roles of Thiol Esters in Cholesterol Biosynthesis Draw a mechanism for each of the three reactions, detailing the pathway for the synthesis of mevalonate from acetyl-CoA.

Lowering Serum Cholesterol Levels with Statins Patients treated with a statin drug generally exhibit a dramatic lowering of serum cholesterol. However, the amount of the enzyme HMG-CoA reductase present in cells can increase substantially. Suggest an explanation for this effect.

Net Synthesis of $\alpha$-Ketoglutarate

$\alpha$-Ketoglutarate plays a central role in the biosynthesis of several amino acids. Write a sequence of enzymatic reactions that could result in the net synthesis of $\alpha$-ketoglutarate from pyruvate. Your proposed sequence must not involve the net consumption of other citric acid cycle intermediates. Write an equation for the overall reaction and identify the source of each reactant.

Net Synthesis of $\alpha$-Ketoglutarate $\alpha$-Ketoglutarate plays a central role in the biosynthesis of several amino acids. Write a sequence of enzymatic reactions that could result in the net synthesis of $\alpha$-ketoglutarate from pyruvate. Your proposed sequence must not involve the net consumption of other citric acid cycle intermediates. Write an equation for the overall reaction and identify the source of each reactant.

Classify each of the following reactions as (1) a redox reaction (2) a nonredox reaction or (3) “can’t classify” because of insuffi cient information.

a. A combination reaction in which one reactant is an element

b. A decomposition reaction in which the products are all elements

c. A decomposition reaction in which one of the products is an element

d. A displacement reaction in which both of the reactants are compounds

Regulation of Cholesterol Biosynthesis Cholesterol in humans can be obtained from the diet or synthesized de novo. An adult human on a low-cholesterol diet typically synthesizes $600 \mathrm{mg}$ of cholesterol per day in the liver. If the amount of cholesterol in the diet is large, de novo synthesis of cholesterol is drastically reduced. How is this regulation brought about?

Energy Cost of a Cycle of Glycolysis and Gluconeogenesis

What is the cost (in ATP equivalents) of transforming glucose to pyruvate via glycolysis and back again to glucose via gluconeogenesis?

Pathway of Atoms in Gluconeogenesis A liver extract capable of carrying out all the normal metabolic reactions of the liver is briefly incubated in separate experiments with the following ${ }^{14} \mathrm{C}$-labeled precursors.
Trace the pathway of each precursor through gluconeogenesis. Indicate the location of ${ }^{14} \mathrm{C}$ in all intermediates and in the product, glucose.

Regulation of the Calvin Cycle Iodoacetate reacts irreversibly with the free - $\mathrm{SH}$ groups of Cys residues in proteins. Predict which Calvin cycle enzyme(s) would be inhibited by iodoacetate, and explain why.

In the chemical reaction for photosynthesis, what are the reactants and what are the products?