Organic Chemistry

Section 25.6 Pyridoxal Phosphate: Vitamin B 6 1059

PROBLEM 12

Taking into account the pathway for phenylalanine degradation, answer the following

questions:

a. What coenzyme and what other organic compound are needed by tyrosine amino-

transferase?

b. What bond in homogentisate is oxidized by homogentisate dioxygenase? (Hint:Keto-enol

tautomerism occurs after oxidation.)

c. What compound is used to supply the methyl group needed to convert noradrenaline into

adrenaline? (Hint:See Section 10.11.)

PROBLEM 13

acids other than can be used to accept the amino group from pyri-

doxamine in enzyme-catalyzed transaminations. What amino acids are formed from the

following acids?

Mechanism for Racemization
The first step in the PLP-catalyzed racemization of an L-amino acid is the same as the
first step in the PLP-catalyzed transamination of an amino acid—removal of a proton
from the of the amino acid bound to PLP. In the second step of racemization,
reprotonation occurs on the The proton can be donated to the hybridized
from either side of the plane defined by the double bond. Consequently, both
D- and L-amino acids are formed. In other words, the L-amino acid is racemized.

a-carbon

a-carbon. sp^2

a-carbon

O O

pyruvate

CO−

O O O

oxaloacetate

−OCCH

2 CCO

CH −

3 C

a-keto

a-Keto a-ketoglutarate

formed from dopa, which in turn is formed from the transami-

nation of tyrosine. Half of untreated phenylketonurics are dead

by age 20. When a woman with PKU becomes pregnant, she

must return to the low phenylalanine diet she had as a child, be-

cause a high level of phenylalanine can cause abnormal devel-

opment of the fetus.

Another genetic disease that results from a deficiency of an

enzyme in the pathway for phenylalanine degradation is al-

captonuria, which is caused by lack of homogentisate dioxy-

genase. The only ill effect of this enzyme deficiency is black

urine. The urine of those afflicted with alcaptonuria turns

black because the homogentisate they excrete immediately

oxidizes in the air.

About 3 days after they begin drinking milk, all babies born

in the United States are tested for high serum phenylalanine

levels, which would indicate a buildup of phenylalanine. If a

baby is found to lack phenylalanine hydroxylase, he or she is

immediately put on a diet low in phenylalanine and high in ty-

rosine. As long as the phenylalanine level is kept under careful

control for the first 5 to 10 years of life, the baby will experi-

ence no adverse effects.

If the diet is not controlled, however, the baby will be se-

verely mentally retarded by the time he or she is a few months

old. Untreated children have paler skin and fairer hair than

other members of their family because they don’t synthesize ty-

rosine, so their melanin levels are low. Melanin is the precursor

of the compound responsible for skin pigmentation. Melanin is

transimination

O

O

+N

H

+N

H

+N

H

C

H

RCO−

O

CO−

O

CO−

E

(CH 2 ) 4

+ RCHCO−

+NH 3

B

N

H

RC

H

RCH

B−

mechanism for PLP-catalyzed racemization of an L-amino acid

B−

with E (CH 2 ) 4 NH 2

N

HC H

O

N

HC H

O

N

HC H

O

N
HC H
O
PiO

CH 3

PiO

CH 3

PiO

CH 3

PiO

CH 3

racemized

amino acid