The Organic Chemistry of Metabolic Pathways

PROBLEM 29-1One of the steps in fat metabolism is the reaction of glycerol (1,2,3-propane-triol) with ATP to yield glycerol 1-phosphate. Write the reaction, and draw thestructure of glycerol 1-phosphate.

PROBLEM 29-2Write the equations for the remaining passages of the  oxidation pathway following those shown in Figure 29-4.

PROBLEM 29-3 How many molecules of acetyl $\mathbf{CoA}$ are produced by catabolism of the following fatty acids, and how many passages of the $\mathbf{\beta }\mathbf{-}$oxidation pathway are needed?

(a) Palmitic acid, ${\mathbf{CH}}_{\mathbf{3}}{\mathbf{\left(}{\mathbf{CH}}_{\mathbf{2}}\mathbf{\right)}}_{\mathbf{14}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$.

(b) Arachidic acid, ${\mathbf{CH}}_{\mathbf{3}}{\mathbf{\left(}{\mathbf{CH}}_{\mathbf{2}}\mathbf{\right)}}_{\mathbf{18}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$.

PROBLEM 29-4 Write a mechanism for the dehydration reaction of $\mathbf{\beta }\mathbf{-}$hydroxybutyryl ACP to yield crotonyl ACP in step 7 of fatty-acid synthesis.

PROBLEM 29-5 Evidence for the role of acetate in fatty-acid biosynthesis comes from isotope labelling experiments. If acetate labelled within the methyl group (${}^{\mathbf{3}}\mathbf{CH}_{\mathbf{3}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}$) were incorporated into fatty acids, at what positions in the fatty-acid chain would you expect the ${}^{\mathbf{13}}\mathbf{C}$ label to appear?

PROBLEM 29-6 Does the reduction of acetoacetyl ACP in step 6 occur on the Re face or the Siface of the molecule?

PROBLEM 29-7 Identify the two steps of glycolysis in which ATP is produced.

PROBLEM 29-8 Look at the entire glycolysis pathway, and make a list of the kinds of organic reactions that take place-nucleophilic acyl substitutions, aldol reactions, E1cB reactions, and so forth.

PROBLEM 29-9 Which carbon atoms in glucose end up as $\mathbf{-}{\mathbf{CH}}_{\mathbf{3}}$ carbons in acetyl CoA? Whichcarbons end up as ${\mathbf{CO}}_{\mathbf{2}}$ ?

Which of the substances in the citric acid cycle are tricarboxylic acids, thus giving the cycle its alternative name?

Is the pro-R or pro-S hydrogen removed from citrate during the dehydration in step 2 of the citric acid cycle? Does the elimination reaction occur with syn or anti geometry?

Write a mechanism for step 6 of gluconeogenesis, the reduction of 3-phoshoglyceryl phosphate with NADH/H⁺ to yield glyceraldehyde 3-phosphate.

Write a mechanism for step 6 of gluconeogenesis, the reduction of 3-phoshoglyceryl phosphate with NADH/H⁺ to yield glyceraldehyde 3-phosphate.

What α-keto acid is formed on transamination of leucine?

Question: Which of the following base sequences would most likely be recognized by a restriction endonuclease? Explain.

(a) GAATTC 

(b) GATTACA 

(c) CTCGAG

For what amino acids do the following ribonucleotide triplets code?

(a) AAU 

(b) GAG 

(c) UCC 

(d) CAU

Question: From what DNA sequences were each of the mRNA codons in Problem 28-26 transcribed?

Question: What anticodon sequences of tRNAs are coded for by the codons in Problem 28-26?

Question: Draw the complete structure of the deoxyribonucleotide sequence from which the mRNA codon in Problem 28-29 was transcribed

Give an mRNA sequence that will code for the synthesis of metenkephalin.

Tyr-Gly-Gly-Phe-Met

Give an mRNA sequence that will code for the synthesis of angiotensin II.

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

What amino acid sequence is coded for by the following DNA coding strand (sense strand)?

$\left(5^{\text{'}}\right)\mathbf{\text{CTT-CGA}}\mathbf{-}\mathbf{\text{CCA-GAC-AGC}}\mathbf{-}\mathbf{\text{TTT}}\left(3^{\text{'}}\right)$

Draw the structure of adenosine 5’-monophosphate (AMP), an intermediate in some biochemical pathways.

Cyclic adenosine monophosphate (cyclic AMP), a modulator of hormone action, is related to AMP (Problem 29-35) but has its phosphate group linked to two hydroxyl groups at C3’ and C5’ of the sugar. Draw the structure of cyclic AMP.

What general kind of reaction does ATP carry out?

What general kind of reaction does NAD⁺ carry out?

What general kind of reaction does FAD carry out?

What enzyme cofactor is associated with each of the following kinds of reactions?

(a) Transamination

(b) Carboxylation of a ketone

(c) Decarboxylation of an  $\mathit{\alpha }\mathbf{-}\mathbf{\text{keto acid }}$

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.

Why aren’t the glycolysis and gluconeogenesis pathways the exact reverse of each other?

In glycerol metabolism, the oxidation of sn-glycerol 3-phosphate to give dihydroxyacetone phosphate is catalyzed by sn-glycerol-3-phosphate dehydrogenase, with NAD1 as a 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:

The initial reaction in Problem 29-52, conversion of two molecules of acetyl CoA to one molecule of acetoacetyl CoA, is a Claisen reaction. Assuming that there is a base present, show the mechanism of the reaction.

In step 6 of fatty-acid biosynthesis (Figure 29-5), 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?

Human brain natriuretic peptide (BNP) is a small peptide of  $\mathbf{32}$ amino acids used in the treatment of congestive heart failure. How many nitrogen bases are present in the DNA that codes for BNP?

Human and horse insulin both have two polypeptide chains, with one chain containing $\mathbf{21}$ amino acids and the other containing   $\mathbf{30}$ amino acids. They differ in primary structure at two places. At the position data-custom-editor="chemistry" $\mathbf{9}$ in one chain, human insulin has Ser and horse insulin has Gly; at the position data-custom-editor="chemistry" $\mathbf{30}$ in the other chain, human insulin has Thr and horse insulin has Ala. How must the DNA for the two insulins differ?

The DNA of sea urchins contains about $\mathbf{32}\mathbf{\%}$A. What percentages of the other three bases would you expect in sea urchin DNA? Explain.

The codon UAA stops protein synthesis. Why does the sequence UAAin the following stretch of mRNA not cause any problems?

-GCA-UUC-GAG-GUA-ACG-CCC-

In step 7 of fatty-acid biosynthesis (Figure 29-5), dehydration of a b-hydroxy thioester occurs to give trans-crotonyl ACP. Is the dehydrationa syn elimination or an anti elimination?

In step 8 of fatty-acid biosynthesis (Figure 29-5), reduction of transcrotonyl ACP gives butyryl ACP. A hydride from NADPH adds to C3 ofthe crotonyl group from the Re face, and protonation on C2 occurs onthe Si face. Is the reduction a syn addition or an anti addition?