Organic Chemistry

PROBLEM 21

Thiols such as ethanethiol and propanethiol can be used to reduce vitamin K epoxide back

to vitamin KH 2 ,but they react much more slowly than dihydrolipoate. Explain.

1070 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

Vitamin K epoxide is reduced back to vitamin by an enzyme that uses the

coenzyme dihydrolipoate as the reducing agent. The epoxide is first reduced to vita-

min K, which is then further reduced to vitamin

Warfarin and dicoumarol are used clinically as anticoagulants. Warfarin is also a

common rat poison, causing death by internal bleeding. These compounds prevent

clotting by inhibiting the enzyme that reduces vitamin K epoxide to vitamin

thereby preventing the carboxylation of glutamate. The enzyme cannot tell the differ-

ence between these two compounds and vitamin K epoxide, so the compounds act as

competitive inhibitors.

Vitamin E has recently been found to be an anticoagulant. It directly inhibits the

enzyme that carboxylates glutamate residues.

CH 2 CCH 3

O O O

OH

OOOO

OH OH

warfarin dicoumarol

KH 2 ,

KH 2.

KH 2

TOO MUCH BROCCOLI

An article describing two women with diseases

characterized by abnormal blood clotting reported

that they did not improve when they were given warfarin. When

questioned about their diets, one woman said that she ate at

least a pound (0.45 kg) of broccoli every day, and the other ate

broccoli soup and a broccoli salad every day. When broccoli

was removed from their diets, warfarin became effective in pre-

venting the abnormal clotting of their blood. Because broccoli

is high in vitamin K, these patients had been getting enough di-

etary vitamin K to compete with the drug, thereby making the

drug ineffective.

O

O

SH

O

O

R

OH

OH

R

SS

R′ R′

SH SH SS

R′ R′

SH

+ H 2 O

O

R

vitamin K epoxide vitamin K vitamin KH 2