29 • Additional Problems
29 • Additional Problems
Visualizing Chemistry
Identify the following intermediate in the citric acid cycle, and tell whether it has R or S stereochemistry:
The following compound is an intermediate in the biosynthesis of one of the 20 common α-amino acids. Which one is it likely to be, and what kind of chemical change must take place to complete the biosynthesis?
The following compound is an intermediate in the pentose phosphate pathway, an alternative route for glucose metabolism. Identify the sugar it is derived from.
Mechanism Problems
In the pentose phosphate pathway for degrading sugars, ribulose 5-phosphate is converted to ribose 5-phosphate. Propose a mechanism for the isomerization.
Another step in the pentose phosphate pathway for degrading sugars (see Problem 29-21) is the conversion of ribose 5-phosphate to glyceraldehyde 3-phosphate. What kind of organic process is occurring? Propose a mechanism for the conversion.
One of the steps in the pentose phosphate pathway for glucose catabolism is the reaction of sedoheptulose 7-phosphate with glyceraldehyde 3-phosphate in the presence of a transaldolase to yield erythrose 4-phosphate and fructose 6-phosphate.
One of the steps in the pentose phosphate pathway for glucose catabolism is the reaction of xylulose 5-phosphate with ribose 5-phosphate in the presence of a transketolase to give glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate.
The amino acid tyrosine is biologically degraded by a series of steps that include the following transformations:
The double-bond isomerization of maleoylacetoacetate to fumaroylacetoacetate is catalyzed by practically any nucleophile, :Nu–. Propose a mechanism.
Design your own degradative pathway. You know the rules (organic mechanisms), and you’ve seen the kinds of reactions that occur in the biological degradation of fats and carbohydrates into acetyl CoA. If you were Mother Nature, what series of steps would you use to degrade the amino acid serine into acetyl CoA?
The amino acid serine is biosynthesized by a route that involves reaction of 3-phosphohydroxypyruvate with glutamate to give 3-phosphoserine. Propose a mechanism.
The amino acid leucine is biosynthesized from α-ketoisocaproate, which is itself prepared from α-ketoisovalerate by a multistep route that involves (1) reaction with acetyl CoA, (2) hydrolysis, (3) dehydration, (4) hydration, (5) oxidation, and (6) decarboxylation. Show the steps in the transformation, and propose a mechanism for each.
The amino acid cysteine, C3H7NO2S, is biosynthesized from a substance called cystathionine by a multistep pathway.
Enzymes and Coenzymes
Lactate, a product of glucose catabolism in oxygen-starved muscles, can be converted into pyruvate by oxidation. What coenzyme do you think is needed? Write the equation in the normal biochemical format using a curved arrow.
Metabolism
In step 2 of the citric acid cycle (Figure 29.14), cis-aconitate reacts with water to give (2R,3S)-isocitrate. Does –OH add from the Re face of the double bond or from the Si face? What about –H? Does the addition of water occur with syn or anti geometry?
General Problems
In glycerol metabolism, the oxidation of sn-glycerol 3-phosphate to give dihydroxyacetone phosphate is catalyzed by sn-glycerol-3-phosphate dehydrogenase, with NAD+ as cofactor. The reaction is stereospecific, occurring exclusively on the Re face of the nicotinamide ring.
Which hydrogen in the NADH product comes from sn-glycerol 3-phosphate? Does it have pro-R or pro-S stereochemistry?
The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield CO2. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA:
In step 6 of fatty-acid biosynthesis (Figure 29.6), acetoacetyl ACP is reduced stereospecifically by NADPH to yield an alcohol. Does hydride ion add to the Si face or the Re face of acetoacetyl ACP?
In step 7 of fatty-acid biosynthesis (Figure 29.6), dehydration of a β-hydroxy thioester occurs to give trans-crotonyl ACP. Is the dehydration a syn elimination or an anti elimination?
In step 8 of fatty-acid biosynthesis (Figure 29.6), reduction of trans-crotonyl ACP gives butyryl ACP. A hydride from NADPH adds to C3 of the crotonyl group from the Re face, and protonation on C2 occurs on the Si face. Is the reduction a syn addition or an anti addition?