Five coenzymes are required by a -ketoglutarate

Answer the following: a. What coenzyme transfers an acyl group from one substrate to another? b. What is the function of FAD in the pyruvate dehydrogenase complex? c. What is the function of NAD + in the pyruvate dehydrogenase complex? d. What reaction necessary for proper blood clotting is catalyzed by vitamin KH 2 ? e. What coenzymes are used for decarboxylation reactions? f. What kinds of substrates do the decarboxylating coenzymes work on? g. What coenzymes are used for carboxylation reactions? h. What kinds of substrates do the carboxylating coenzymes work on?

Name the coenzymes that a. allow electrons to be delocalized. c. provide a strong base. b. are oxidizing agents. d. donate one-carbon groups.

For each of the following reactions, name both the enzyme that catalyzes the reaction and the required coenzyme:

S -Adenosylmethionine (SAM) is formed from the reaction of methionine with ATP ( Section 9.9 ) . The other product of the reaction is triphosphate. Propose a mechanism for this reaction.

Five coenzymes are required by a -ketoglutarate dehydrogenase, the enzyme in the citric acid cycle that converts a -ketoglutarate to succinyl-CoA. a. Identify the coenzymes. b. Propose a mechanism for the reaction.

Five coenzymes are required by a -ketoglutarate dehydrogenase, the enzyme in the citric acid cycle that converts a -ketoglutarate to succinyl-CoA. a. Identify the coenzymes. b. Propose a mechanism for the reaction.

Propose a mechanism for the following reaction:

When transaminated, the three branched-chain amino acids (valine, leucine, and isoleucine) form compounds that have the characteristic odor of maple syrup. An enzyme known as branched-chain a -keto acid dehydrogenase converts these compounds into CoA esters. People who do not have this enzyme have the genetic disease known as maple syrup urine disease, so called because their urine smells like maple syrup. a. Draw the compounds that smell like maple syrup. b. Draw the CoA esters. c. Branched-chain a -keto acid dehydrogenase has i ve coenzymes. Identify them. d. Suggest a way to treat maple syrup urine disease.

Draw the products of the following reaction, where T is tritium:

When UMP is dissolved in T 2 O, exchange of T for H occurs at the 5-position. Propose a mechanism for this exchange. (T = 3 H; see Problem 31 ).

Dehydratase is a PLP-requiring enzyme that catalyzes an a , b -elimination reaction. Propose a mechanism for this reaction.

In addition to the reactions mentioned in Section 24.5 , PLP can catalyze b -substitution reactions. Propose a mechanism for the following PLP-catalyzed b -substitution reaction:

PLP can catalyze both a , b -elimination reactions ( Problem 33 ) and b , g -elimination reactions. Propose a mechanism for the following PLP-catalyzed b , g -elimination:

The glycine cleavage system is a group of four enzymes that together catalyze the following reaction: glycine cleavage system glycine + THF N CO2 5 ,N 10-methylene-THF + Use the following information to determine the sequence of reactions carried out by the glycine cleavage system: a. The i rst enzyme is a PLP-requiring decarboxylase. b. The second enzyme is aminomethyltransferase. This enzyme has a lipoate coenzyme. c. The third enzyme synthesizes N 5 , N 10 -methylene-THF and also forms +NH4 . d. The fourth enzyme is an FAD-requiring enzyme. e. The cleavage system also requires NAD+

Nonenzyme-bound FAD is a stronger oxidizing agent than NAD+ . How, then, can NAD+ oxidize the reduced flavoenzyme in the pyruvate dehydrogenase complex?

FADH 2 reduces a , b -unsaturated thioesters to saturated thioesters. The reaction is thought to take place by a mechanism that involves radicals. Propose a mechanism for this reaction.

Problem 1P How does the metal ion in carboxypeptidase A increase the enzyme’s catalytic activity?

What is the product of the following reaction?

What is the product of the following reaction?

Problem 4P How many conjugated double bonds are there in a. FAD? ________________ b. FADH2?

Problem 5P Instead of adding to the 4a position and protonating N-5, the thiolate ion could have added to the 10a position and protonated N-1. Why is addition to the 4a position favored? (Hint: Which nitrogen is a stronger base?)

Problem 7P Explain why the hydrogens of the C-8 methyl group are more acidic than those of the C-7 methyl group.

Draw structures that show the similarity between the decarboxylation of the pyruvate–TPP intermediate and the decarboxylation of a -keto acid. Equation Transcription: Text Transcription: beta

Acetolactate synthase is another TPP-requiring enzyme. It, too, catalyzes the decarboxylation of pyruvate, but it transfers the resulting acyl group to another molecule of pyruvate, forming acetolactate. This is the first step in the biosynthesis of the amino acids valine and leucine. Propose a mechanism for this reaction.

Acetolactate synthase can also transfer the acyl group from pyruvate to \(\alpha\) -ketobutyrate. This is the first step in the formation of the amino acid isoleucine. Propose a mechanism for this reaction. Equation Transcription: Text Transcription: alpha

\(\alpha\)-Keto acids other than -ketoglutarate can accept the amino group from pyridoxamine in enzyme-catalyzed transamination reactions. What amino acids are formed when the following \(\alpha\)-keto acids accept the amino group? Equation Transcription: Text Transcription: alpha

The PLP-requiring enzyme that catalyzes the Ca — Cb bond cleavage reaction that converts serine to glycine removes the substituent bonded to the a -carbon in the first step of the reaction. Starting with PLP bound to serine in an imine linkage, propose a mechanism for this reaction. ( Hint: The first step involves general-base catalyzed removal of the proton from serine’s OH group.)

Propose a mechanism for the PLP-catalyzed \(\alpha, \beta\)-elimination reaction shown on page \(1152\). Equation Transcription: Text Transcription: Alpha, beta 1152

Which compound is more easily decarboxylated?

Problem 16P Explain why the ability of PLP to catalyze an amino acid transformation is greatly reduced if a PLP-requiring enzymatic reaction is carried out at a pH at which the pyridine nitrogen is not protonated.

Problem 17P Explain why the ability of PLP to catalyze an amino acid transformation is greatly reduced if the OH substituent of pyridoxal phosphate is replaced by OCH3 .

Ethanolamine ammonia lyase, a coenzyme B \(12\) –requiring enzyme, catalyzes the following reaction. Propose a mechanism for this reaction. Equation Transcription: Text Transcription: 12

A fatty acid with an even number of carbons is metabolized to acetyl-CoA, which can then enter the citric acid cycle to be further metabolized ( Section \(25.10\) ) . A fatty acid with an odd number of carbons is metabolized to acetyl-CoA and one equivalent of propionyl-CoA. Propionyl-CoA cannot enter the citric acid cycle. Two coenzyme-requiring enzymes are needed to convert it into succinyl-CoA, a compound that can enter the citric acid cycle. Write the two enzyme-catalyzed reactions and include the names of the required coenzymes. Equation Transcription: Text Transcription: 25.10

Problem 20P How do the structures of folic acid and aminopterin differ?

Problem 21P What is the source of the methyl group in thymidine?

Problem 22P Thiols such as ethanethiol and propanethiol can be used to reduce vitamin K epoxide to vitamin KH2 , but they react much more slowly than dihydrolipoate. Explain why this is so.

Problem 23P Answer the following: a. What coenzyme transfers an acyl group from one substrate to another? b. What is the function of FAD in the pyruvate dehydrogenase complex? c. What is the function of NAD+ in the pyruvate dehydrogenase complex? d. What reaction necessary for proper blood clotting is catalyzed by vitamin KH2 ? e. What coenzymes are used for decarboxylation reactions? f. What kinds of substrates do the decarboxylating coenzymes work on? g. What coenzymes are used for carboxylation reactions? h. What kinds of substrates do the carboxylating coenzymes work on?

Problem 24P Name the coenzymes that a. allow electrons to be delocalized. c. provide a strong base. b. are oxidizing agents. d. donate one-carbon groups.

For each of the following reactions, name both the enzyme that catalyzes the reaction and the required coenzyme:

S -Adenosylmethionine (SAM) is formed from the reaction of methionine with ATP (Section \(9.9\)). The other product of the reaction is triphosphate. Propose a mechanism for this reaction. Equation Transcription: Text Transcription: 9.9

Problem 28P What acyl groups have we seen transferred by reactions that require thiamine pyrophosphate as a coenzyme? ( Hint: See Problems 9 , 10 , 27, and 30 .)

Five coenzymes are required by \(\alpha\) -ketoglutarate dehydrogenase, the enzyme in the citric acid cycle that converts \(\alpha\) -ketoglutarate to succinyl-CoA. a. Identify the coenzymes. b. Propose a mechanism for the reaction. Equation Transcription: Text Transcription: alpha

Propose a mechanism for the following reaction:

When transaminated, the three branched-chain amino acids (valine, leucine, and isoleucine) form compounds that have the characteristic odor of maple syrup. An enzyme known as branched-chain a -keto acid dehydrogenase converts these compounds into CoA esters. People who do not have this enzyme have the genetic disease known as maple syrup urine disease, so called because their urine smells like maple syrup. a. Draw the compounds that smell like maple syrup. b. Draw the CoA esters. c. Branched-chain a -keto acid dehydrogenase has i ve coenzymes. Identify them. d. Suggest a way to treat maple syrup urine disease.

Draw the products of the following reaction, where T is tritium: (Hint: Tritium is \({ }^{3} \mathrm{H}\), a hydrogen atom with two neutrons. Although a C—T bond breaks more slowly than a C—H bond, it is still the first bond in the substrate that breaks.) Equation Transcription: 3H Text Transcription: ^3 H

When UMP is dissolved in \(\mathrm{T}_{2} \mathrm{O}\), exchange of T for H occurs at the 5-position. Propose a mechanism for this exchange. (\(\mathrm{T}={ }^{3} \mathrm{H}\); see Problem \(31\)). Equation Transcription: T2O T = 3H Text Transcription: T_2O T = ^3H 31

Dehydratase is a PLP-requiring enzyme that catalyzes an \(\alpha, \beta\)-elimination reaction. Propose a mechanism for this reaction. Equation Transcription: Text Transcription: alpha,beta

In addition to the reactions mentioned in Section \(24.5\) , PLP can catalyze \(\beta\)-substitution reactions. Propose a mechanism for the following PLP-catalyzed \(\beta\)-substitution reaction: Equation Transcription: Text Transcription: 24.5 beta

PLP can catalyze both \(\alpha, \beta\)-elimination reactions (Problem \(33\)) and \(\beta, \gamma\)-elimination reactions. Propose a mechanism for the following PLP-catalyzed \(\beta, \gamma\)-elimination: Equation Transcription: Text Transcription: alpha,beta 33 beta,gamma

The glycine cleavage system is a group of four enzymes that together catalyze the following reaction: glycine + THF glycine cleavage system \(N^{5}, N^{10}\) -methylene-THF + \(\mathrm{CO}_{2}\) Use the following information to determine the sequence of reactions carried out by the glycine cleavage system: a. The first enzyme is a PLP-requiring decarboxylase. b. The second enzyme is aminomethyltransferase. This enzyme has a lipoate coenzyme. c. The third enzyme synthesizes \(N^{5}, N^{10}\)-methylene-THF and also forms \({ }^{+} \mathrm{NH}_{4}\). d. The fourth enzyme is an FAD-requiring enzyme. e. The cleavage system also requires \(\mathrm{NAD}^{+}\). Equation Transcription: N5,N10 CO2 +NH4 NAD+ Text Transcription: N_5,N_10 CO_2 ^+NH_4 NAD^+

Problem 37P Nonenzyme-bound FAD is a stronger oxidizing agent than NAD+ . How, then, can NAD+ oxidize the reduced flavoenzyme in the pyruvate dehydrogenase complex?

\(\mathrm{FADH}_{2}\) reduces \(\alpha, \beta\)-unsaturated thioesters to saturated thioesters. The reaction is thought to take place by a mechanism that involves radicals. Propose a mechanism for this reaction. Equation Transcription: FADH2 Text Transcription: FADH_2 alpha,beta