Biology of Disease

Vitamin B 12 or cobalamin is an unusual molecule in that it contains an

organometallic bond between cobalt and carbon (Figure 13.18 (A)). A close

relationship exists between the functions of vitamin B 12 and folic acid and,

to some extent at least, they depend on each other for activation. Organic

one carbon groups, for example methyl (CH 3 –), methylene (–CH 2 -), methenyl

(–CH=), formyl (–CHO), formate (–COO–) and formino (–CHNH), are generally

toxic. In metabolism, they are bound to carriers derived from vitamin B 12 and

folic acid, which allows them to be converted to different oxidation states and

used in a variety of different reactions in a nontoxic manner. These reactions

are necessary for the catabolism of some amino acids, for the formation of

a number of proteins and the synthesis of purine and pyrimidine bases and

therefore nucleotides and nucleic acids. Unlike vitamin B 12 and folic acid that

carry organic one carbon compounds, vitamin H or biotin (Figure 10.15) is

required to form the prosthetic group that carries CO 2 in a number of enzymes.

These include acetyl CoA carboxylase and pyruvate decarboxylase which are

key enzymes of fatty acid synthesis and gluconeogenesis, the production of

glucose from noncarbohydrate precursors.

Vitamin C or ascorbic acid (Figure 10.16) is required to reduce metal ions in a

number of enzymes following catalysis. Prolyl and lysyl hydroxylases contain

Fe2+(II) which is oxidized to Fe3+(III) during hydroxylation reactions involved

in cross-linking collagen molecules, which adds strength to connective

tissues. Ascorbate reduces their iron back to the ferrous state, regenerating

an active enzyme. Similarly, the Cu2+(II) in enzymes involved in synthesis of

catecholamine hormones (Chapter 7) is returned to the Cu+(I) state following

the oxidation of the copper during catalysis. The antioxidant properties of

ascorbic acid, in association with vitamin E, help protect lipids in the cell

membranes and blood lipoproteins from oxidative damage. It also enhances

the absorption of iron and regulates the absorption of copper from the GIT.

Several vitamers, retinol, retinaldehyde or retinal and retinoic acid, show

vitamin A activities. Retinol (Figure 10.17 (A)) can be metabolically converted

to retinaldehyde, which, in turn can be oxidized to retinoic acid. In addition,

the provitamin A carotenoids, for example A carotene (Figure 10.17 (B)),

can be converted to active forms in the liver. Retinoic acid helps regulate

the proliferation and development of cells in a tissue specific manner that

resembles the actions of steroid hormones (Chapter 7). It binds to nuclear

receptors, which then interact with DNA and activate specific genes. Vitamin

A is associated with the development of epithelial cells, such as the skin and

the mucosal membranes that cover internal and external surfaces of the

body and have numerous functions, for example, as structural barriers that

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H

H

H

H

N

N

H

H

H

S O

CH 2

CH 2

CH 2

CH 2

O

C

O-

Figure 10.15 The structure of vitamin H (biotin).

O

H

H

C

OH

HO

O

OH

HOH 2 C

Figure 10.16 The structure of vitamin C (ascorbic

acid).

Figure 10.17 The structures of (A) vitamin A (retinol) and (B) A carotene.

B) CH 3

CH 3 CH (^3) CH
3
H 3 C CH (^3) CH 3 CH 3
H 3 C
H 3 C
CH 3
H 3 C CH 3 CH 3 CH 3
CH 2 OH
A)