Biology of Disease

INVESTIGATING NUTRITIONAL DISORDERS

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY '+.

Figure 10.38 The catabolism of xanthurenic acid,

which is the basis of the tryptophan load test for

vitamin B 6 status. See text for details.

H 2 O

H 2 O

COOH

OH

OH

N

OH

COOH

NH 2

H

CH 2 CH COO-

N

NH 3

H 3 NCH

CH 3

+ COO-

Tryptophan

dioxygenase and

formylkynurenine

formamidase

activities

Tryptophan

Kynurenine

aminotransferase

Kynurenine

Kynurenine

hydroxylase

3-Hydroxykynurenine

Kynureninase

3-Hydroxyanthranilic acid

COOH

OH

N

Kynurenic acid

Xanthurenic acid

Vitamin B 6

deficiency

Alanine

NADPH + H+

NADP+

Kynurenine

aminotransferase

Inhibition

is not a reliable indicator of status. Changes in urinary excretion of biotin or
of its metabolites are better indicators of biotin status.

Folic acid status may be investigated by directly measuring its concentration
in serum or erythrocytes although these are associated with a number of
problems. Serum folic acid tends to reflect dietary intake over the previous
few weeks. Patients with both acquired and inherited folic acid deficiency may
remain moderately deficient for months or years, taking in just enough folic
acid to prevent low erythrocyte folic acid concentrations and frank anemia.
Erythrocyte values are not sensitive to short-term variations; depletion
occurs only in the later stages of deficiency and is usually accompanied by
megaloblastic anemia. Both erythrocyte and serum folic acid studies must
be performed. Severe folic acid deficiency is accompanied by a macrocytic
anemia (Chapter 13) although the size of erythrocytes may be entirely normal
in lesser degrees of depletion. Serum vitamin B 12 concentrations should also
be measured when evaluating folic acid deficiency since if either vitamin
is deficient it can lead to a failure in absorption by megaloblastic intestinal
cells resulting in a secondary deficiency of the other. Formiminoglutamic
acid (FIGLU) is a substrate for the folic acid dependent enzyme, formimino-