Organic Chemistry

1034 CHAPTER 25 The Organic Mechanisms of the Coenzymes • Metabolism

coenzymes play a variety of chemical roles that the amino acid side chains of enzymes

cannot play. Some coenzymes function as oxidizing and reducing agents, some allow

electrons to be delocalized, some activate groups for further reaction, and some pro-

vide good nucleophiles or strong bases needed for a reaction. Because it would be

highly inefficient for the body to use a compound only once and then discard it, coen-

zymes are recycled. Therefore, we will see that any coenzyme that is changed during

the course of a reaction is subsequently converted back to its original form.

An enzyme plus the cofactor it requires to catalyze a reaction is called a

holoenzyme. An enzyme that has had its cofactor removed is called an apoenzyme.

Holoenzymes are catalytically active, whereas apoenzymes are catalytically inactive

because they have lost their cofactors.

Early nutritional studies divided vitamins into two classes: water-soluble vita-

mins and water-insoluble vitamins (Table 25.1). Vitamins A, D, E, and K are water

insoluble. Vitamin K is the only water-insoluble vitamin currently known to func-

tion as a coenzyme. Vitamin A is required for proper vision, vitamin D regulates cal-

cium and phosphate metabolism, and vitamin E is an antioxidant. Because they do

not function as coenzymes, vitamins A, D, and E are not discussed in this chapter.

Vitamins A and E are discussed in Sections 9.8 and 26.7, and vitamin D is discussed

in Section 29.6.

Table 25.1 The Vitamins, Their Coenzymes, and Their Chemical Functions

Reaction Human

Vitamin Coenzyme catalyzed deficiency disease

Water-Soluble Vitamins

Niacin (niacinate) Oxidation Pellagra

NADH, NADPH Reduction

Riboflavin (vitamin ) FAD, FMN Oxidation Skin inflammation

Reduction

Thiamine (vitamin ) Thiamine pyrophosphate (TPP) Two-carbon transfer Beriberi

Lipoic acid (lipoate) Lipoate Oxidation —

Dihydrolipoate Reduction

Pantothenic acid (pantothenate) Coenzyme A (CoASH) Acyl transfer —

Biotin (vitamin H) Biotin Carboxylation —

Pyridoxine (vitamin ) Pyridoxal phosphate (PLP) Decarboxylation Anemia

Transamination

Racemization

bond cleavage

Vitamin Coenzyme Isomerization Pernicious anemia

Folic acid (folate) Tetrahydrofolate (THF) One-carbon transfer Megaloblastic anemia

Ascorbic acid (vitamin C) ——Scurvy

Water-Insoluble (lipid-soluble) Vitamins

Vitamin A ———

Vitamin D ——Rickets

Vitamin E ———

Vitamin K Vitamin KH 2 Carboxylation —

B 12 B 12

b-Substitution

a,b-Elimination

Ca¬Cb

B 6

B 1

FADH 2 , FMNH 2

B 2

NAD+, NADP+