Organic Chemistry

PROBLEM 20

What is the source of the methyl group in thymidine?

25.9 Vitamin Vitamin K

Vitamin K is required for proper clotting of blood. The letter K comes from koagulation,

which is German for “clotting.”A series of reactions utilizing six proteins is involved in

blood clotting. In order for blood to clot, the blood-clotting proteins must bind Vi-

tamin K is required for proper binding. Vitamin K deficiencies are rare because the

vitamin is synthesized by intestinal bacteria. Vitamin K is also found in the leaves of

green plants. Vitamin (the hydroquinone of vitamin K) is the coenzyme form of

the vitamin (Section 20.12).

Vitamin is the coenzyme for the enzyme that catalyzes the carboxylation of

the of glutamate side chains in proteins, forming

g-Carboxyglutamatescomplex Ca^2 +much more effectively than glutamates do. The

g-carbon g-carboxyglutamates.

KH 2

O

O

vitamin K

a quinone

OH

OH

vitamin KH 2

a hydroquinone

KH 2

Ca^2 +

Ca^2 +.

KH 2 :

1068 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

Donald D. Woods (1912–1964)was
born in Ipswich, England, and
received a B.A. and a Ph.D. from
Cambridge University. He worked in
Paul Flores’s laboratory at the
London Hospital Medical College.

for the synthesis of DNA—because their synthesis also requires a THF-coenzyme.

One clinical technique used in chemotherapy to fight cancer calls for the patient to be

given a lethal dose of methotrexate and then to “save”him or her by administering

Trimethoprim is used as an antibiotic because it binds to bacterial dihydrofolate

reductase much more tightly than to mammalian dihydrofolate reductase.

N^5 -formyl-THF.

Paul B. Flores (1882–1971)was
born in London. He moved his
laboratory to Middlesex Hospital
Medical School when a bacterial
chemistry unit was established there.
He was knighted in 1946.

THE FIRST

ANTIBACTERIAL DRUGS

Sulfonamides—commonly known as sulfa drugs—

were introduced clinically in 1934 as the first effective antibacte-

rial drugs (Section 30.4). Donald Woods, a British bacteriologist,

noticed that sulfanilamide, initially the most widely used sul-

fonamide, was structurally similar to p-aminobenzoic acid, a

compound necessary for bacterial growth. He proposed that

sulfanilamide’s antibacterial properties were due to its being

able to block the normal utilization of p-aminobenzoic acid.

3-D Molecule:

Vitamin K

a sulfonamide sulfanilamide

H 2 N SNHR

O

O

H 2 NSNH 2

O

O

p-aminobenzoic acid

H 2 N COH

O

Woods and Paul Flores suggested that sulfanilamide acts by

inhibiting the enzyme that incorporates p-aminobenzoic acid

into folic acid. Because the enzyme cannot tell the difference

between sulfanilamide and p-aminobenzoic acid, both com-

pounds compete for the active site of the enzyme. Humans are

not adversely affected by the drug because they do not synthe-

size folate—they get all their folate from their diets.

AU: OK as changed?

As set, it sounds like the drug has no effects on humans.