chapter 38

Vitamin Metabolism

903

TA B LE 38-1 (

c o n tin u e d )

Therapeutic Vitamin

Daily Dose

Disorder^

Biochemical/Biological Defect

Thiamine

2 0

mg

Megaloblastic anemia

Unknown

(vitamin B f;

5-20 mg

Branched-chain

Branched chain a-ketoacid

adult RDA -

1

mg

/ 2 0 0 0

kcal/d)

5-20 mg

>

1 0

mg

ketoaciduria (maple syrup

urine disease)

Pyruvic acidemia

Lactic and pyruvic

acidemia; Leigh’s

encephalomy elopathy

11

decarboxylase

Pyruvate decarboxylase

Pyruvate decarboxylase (low Km

form)

*These disorders can be thought of as relative vitamin deficiency states. Not all patients will respond to vitamins owing to the existence of pheno-

copies. Data from L. E. Rosenberg: Vitamin-responsive inherited metabolic disorders. In

A d v a n c e s in H u m a n G e n e tic s ,

Vol.

6

, H. Harris and

K. Hirschhom, Eds. (Plenum Press, 1976); and S. H. Mudd: Vitamin-responsive genetic abnormalities, In

A d v a n c e s in N u tr itio n a l R e se a rc h ,

Vol. 4

(Plenum Press, 1982).

+A11 disorders have an autosomal recessive pattern of inheritance except as follows:

*X-linked dominant inheritance;

§ Pattern of inheritance unknown;

^Autosomal, probably recessive, inheritance;

‘HX-linked recessive inheritance.

4. The biochemical function of the vitamin should be

related directly to the observed deficiency symptoms,

although this is not always possible to demonstrate.

The classic example is

scurvy

(scorbutus), which used

to be common among sailors who ate no fresh fruit or

vegetables during long sea voyages. Scurvy could be

prevented by consumption of fresh citrus fruits, now

known to be high in vitamin C (ascorbic acid). The

deficiency arose because vitamin C was destroyed by

the methods used to preserve food while at sea. Other

examples of a single vitamin deficiency in human

populations are rare, however, except where the

dietary supply is adequate but utilization of the

vitamin is impaired. Frequently, if one vitamin is

lacking, others are as well, and the intake of protein,

trace elements, and other nutrients is probably

insufficient. This is particularly true of B vitamins.

In addition to nutritional inadequacy, vitamin deficiency

may result from malabsorption, effects of pharmacolo-

gical agents, and abnormalities of vitamin metabolism or

utilization. Thus, in biliary obstruction or pancreatic dis-

ease, the fat-soluble vitamins are poorly absorbed despite

adequate dietary intake because of steatorrhea. Absorp-

tion, transport, activation, and utilization of vitamins re-

quire the participation of enzymes or other proteins whose

synthesis is under genetic control. Dysfunction or absence

of one of these proteins can produce a disease that is

clinically indistinguishable from one caused by dietary

deficiency. In vitamin-dependent or vitamin-responsive

disorders, use of pharmacological doses of the vitamin can

sufficiently overcome the blockage for normal function to

occur (Table 38-1; discussed at the end of the chapter).

Vitamin deficiency can result from treatment with cer-

tain drugs. Thus, destruction of intestinal microorgan-

isms by antibiotic therapy can produce symptoms of

vitamin K deficiency. Isoniazid, used to treat tuberculo-

sis, is a competitive inhibitor of pyridoxal kinase, which

is needed to produce pyridoxal phosphate. Isoniazid can

produce symptoms of pyridoxine deficiency. To prevent

this, pyridoxine is often incorporated into isoniazid tablets.

Methotrexate and related folate antagonists act by compet-

itively inhibiting dihydrofolate reductase (Chapter 27).

Two standards have been established to plan diets that

contain adequate supplies of the vitamins and to aid in

diagnosing vitamin deficiency diseases.

1. The

minimum daily requirement

(MDR) is the

smallest amount of a substance needed by a person to

prevent a deficiency syndrome. It is considered to

represent the body’s basic physiological requirement

of the material. MDR values, which are established

by the U.S. Food and Drug Administration (FDA), are

not available for all vitamins.

2. The

recommended daily allowance

(RDA) is the

amount of a compound needed daily to maintain good

nutrition in most healthy people. RDA values are

intended to serve as nutritional goals, not as dietary

requirements. They are defined by the Food and

Nutrition Board of the National Academy of Sciences