Introduction to Human Nutrition

170 Introduction to Human Nutrition

Assessment of vitamin B 12 status

Measurement of plasma concentrations of vitamin
B 12 is the method of choice, and several simple and
reliable radioligand binding assays have been devel-
oped. A serum concentration of vitamin B 12 below
110 pmol/l is associated with megaloblastic bone
marrow, incipient anemia, and myelin damage. Below
150 pmol/l there are early bone marrow changes,
abnormalities of the deoxyuridine monophosphate
(dUMP) suppression test (see Section 8.11) and
methylmalonic aciduria after a valine load.

The Schilling test for vitamin B 12 absorption
The absorption of vitamin B 12 can be determined by
the Schilling test. An oral dose of [^57 Co] or [^58 Co]-
vitamin B 12 is given with a parenteral fl ushing dose of
1 mg of non-radioactive vitamin to saturate body
reserves, and the urinary excretion of radioactivity is
followed as an index of absorption of the oral mate-
rial. Normal subjects excrete 16–45% of the radioac-
tivity over 24 h, whereas patients lacking the intrinsic
factor excrete less than 5%.
The test can be repeated, giving the intrinsic factor
orally together with the radioactive vitamin B 12 ; if the
impaired absorption was due to a simple lack of
intrinsic factor, and not to anti-intrinsic factor anti-
bodies in the saliva or gastric juice, then a normal
amount of the radioactive material should be absorbed
and excreted.

Methylmalonic aciduria
Methylmalonyl-CoA is formed as an intermediate in
the catabolism of valine and by the carboxylation of
propionyl-CoA arising in the catabolism of isoleu-
cine, cholesterol, and (rare) fatty acids with an odd
number of carbon atoms. Normally, it undergoes
vitamin B 12 -dependent rearrangement to succinyl-
CoA, catalyzed by methylmalonyl-CoA mutase.
Vitamin B 12 defi ciency leads to an accumulation of
methylmalonyl-CoA, which is hydrolyzed to methyl-
malonic acid, which is excreted in the urine. Urinary
excretion of methylmalonic acid, especially after a
loading dose of valine, provides a means of assessing
vitamin B 12 nutritional status.

8.11 Folic acid

Folic acid functions in the transfer of one-carbon
fragments in a wide variety of biosynthetic and cata-

bolic reactions; it is therefore metabolically closely

related to vitamin B 12. Defi ciency of either causes

megaloblastic anemia, and the hematological effects

of vitamin B 12 defi ciency are due to disturbance of

folate metabolism.

Apart from liver, the main dietary sources of folate

are fruits and vegetables. Although folate is widely

distributed in foods, dietary defi ciency is not uncom-

mon, and a number of commonly used drugs can

cause folate depletion. More importantly, there is

good evidence that intakes of folate considerably

higher than normal dietary levels reduce the risk of

neural tube defects, and, where cereal products are

not fortifi ed with folate by law, pregnant women are

recommended to take supplements. There is also evi-

dence that high intakes of folate may be effective in

reducing plasma homocysteine in subjects genetically

at risk of hyperhomocystinemia (some 10–20% of the

population), which may reduce the risk of ischemic

heart disease and stroke.

Vitamers and dietary equivalence

As shown in Figure 8.14, folic acid consists of a

reduced pterin linked to p-aminobenzoic acid,

forming pteroic acid. The carboxyl group of the p-

aminobenzoic acid moiety is linked by a peptide bond

to the α-amino group of glutamate, forming pteroyl-

glutamate (PteGlu). The coenzymes may have up to

seven additional glutamate residues linked by γ-

peptide bonds, forming pteroyldiglutamate (PteGlu 2 ),

pteroyltriglutamate (PteGlu 3 ), etc., collectively

known as folate or pteroyl polyglutamate conjugates

(PteGlun).

“Folate” is the preferred trivial name for pteroyl-

glutamate, although both “folate” and “folic acid” may

be used as a generic descriptor to include various

polyglutamates. PteGlu 2 is sometimes referred to as

folic acid diglutamate, PteGlu 3 as folic acid trigluta-

mate, and so on.

HN

N N

H

H

N

O

H 2 N

H 2

C

H

N

H 2

C

H

N CH

COO–

CH 2

CH 2

C O

(Glu)n

Tetrahydrofolate

Figure 8.14 Tetrahydrofolate (folic acid).