Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

IV. Water-Soluble Vitamins
723
FIGURE 23-21 Folic acid. Structures of oxidized and reduced tetrahydrofolic acid (THFA) are shown. The 5 and 10 positions of the molecule are
highlighted because these sites are important to single-carbon transfer. Folic acid is found in foods as γ-linked polyglutamyl folic acid (n ranges from
3 to 5 units). In the intestine, γ-peptidases (also referred to as conjugases) cleave the polyglutamyl residues to the single glutamate (as shown for the
oxidized structure of folic acid). Single carbon units can enter into THFA by a number of routes. Formimino groups can arise from glycine and histidine
degradation. Cylization results in N 5 , N 10 -methenyl THFA. Reduction of this product results in N 5 , N 10 -methylene THFA. This product can also be
derived directly from an aldol-type condensation reaction arising from the conversion of serine to glycine (see Fig. 24-17). This step represents a major
source of single carbon units. Subsequently, all of the forms of methylated THFA may be ultimately reduced to N 3 -methyl THFA.
division and proliferation. As a final step, when 5-methyl
THFA transfers its methyl moiety to vitamin B 12 , one of
the resulting products is the oxidized form of folic acid,
which must be reduced to THFA to reinitiate the cycle.
With regard to vitamin B 12 , the methylated form is also
shown in Figure 23-22 and is the B 12 cofactor utilized in the
THFA-homocysteine transmethylase system. The other reactions
involving vitamin B 12 utilize B 12 as deoxyadenosylcobalamin
( Fig. 23-22 ). An example is methylmalonyl-CoA
mutase. Without B 12 , methylmalonic acid accumulates.
Otherwise, methylmalonic acid is converted to succinyl-CoA
for ultimate use as a metabolic fuel, a reaction that is essential
for the eventual delivery of carbon from odd-chained
fatty acids into the TCA cycle. This is an important process
for animals, such as some herbivores and ruminants, which
depend in part on odd-chain fatty acids as a source of gluconeogenic
precursors.
c . Metabolism
The steps in absorption, transport, and the utilization of
folic acid and vitamin B 12 are more complex than for other
water-soluble vitamins ( Said, 2004 ). In the case of the folic
acid, the conjugated glutamyl residues must be removed
for effective absorption (e.g., to monoglutamyl tetrahydrofolate)
in the jejunum where it is absorbed. Next, folates
enter plasma and are rapidly cleared by the liver and other
organs. Biliary drainage results in a large enterohepatic circulation
of folate ( Scott, 1994 ).
Folic acid is found in circulation primarily as methyltetrahydrofolate.
Thus, it may be assumed that reduction
and methylation are essential steps in the eventual transfer
of folic acid across cellular barriers and membranes.
The enzymes found in the intestinal cells that carry out the
hydrolysis of conjugated glutamyl residues are commonly
referred to as conjugases. Specific serum transport proteins
exist for folic acid and cellular uptake is by active processes
( Said, 2004 ).
For B 12 , the steps important to processing ( Fig. 23-22 )
involve first the release of B 12 from foods under acidic
conditions; vitamin B 12 then binds to proteins produced
by cells of the gastric fundus (and also the pancreas and
salivary gland in some species). Two proteins have been
identified, which have been designated as R protein