Vitamin C Is the Coenzyme for Two Groups of Hydroxylases

Ascorbic acid has specific roles in the copper-containing hydroxylases and the a-ketoglutarate-linked iron-containing hydroxylases. It also increases the activity of a number of other enzymes in vitro, though this is a nonspecific reducing action. In addition, it has a number of nonenzymic effects due to its action as a reducing agent and oxygen radical quencher.

Dopamine P-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu2+; reduction back

CO I

CHOH

CH2OH

Pantothenic acid

Figure 45-18. Pantothenic acid and coenzyme A. * Shows the site of acylation by fatty acids.

CH2 ch2

CO I

CHOH

H3C C CH3 O"

Coenzyme A (CoASH)

ch2oh

ch2oh

ch2oh

ch2oh

CH2OH

OH OH O OH

Ascorbate Monodehydroascorbate

(semidehydroascorbate)

O O Dehydroascorbate

OH OH O OH

Ascorbate Monodehydroascorbate

(semidehydroascorbate)

CH2OH

O O Dehydroascorbate

Figure 45-19. Vitamin C.

to Cu+ specifically requires ascorbate, which is oxidized to monodehydroascorbate. Similar actions of ascorbate occur in tyrosine degradation at the ^-hydroxy-phenylpyruvate hydroxylase step and at the homogenti-sate dioxygenase step, which needs Fe2+ (Figure 30-12).

A number of peptide hormones have a carboxyl terminal amide which is derived from a glycine terminal residue. This glycine is hydroxylated on the a-carbon by a copper-containing enzyme, peptidylglycine hy-droxylase, which, again, requires ascorbate for reduction of Cu2+.

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and proline hydroxylase is also required in formation of osteocalcin and the C1q component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. Trimethyllysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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