Page 135 - Small Animal Clinical Nutrition 5th Edition

136 Small Animal Clinical Nutrition

Folic Acid SOURCES
VetBooks.ir Folic acid was first discovered in 1943 and was classified as vita- conditions. Liver, egg yolks and green vegetables are good
Folate is found in several foods, but is unstable in a variety of
mins B
and B .The structure of folic acid may be subdivid-
11
10
ed into three functional components: the middle group is para-
sources of folate. The vitamin is destroyed by heating, pro-
aminobenzoic acid (PABA), flanked on one side by a pteridine longed freezing and during storage in water. Commercial pet
ring, and on the other side by a polyglutamic acid chain. Folate foods are supplemented with folate to overcome the effects of
is the name commonly used to designate a family of com- processing and storage.
pounds with the biologic activity of folic acid (Brody, 1994a;
Selhub and Rosenberg, 1996). Biotin
Biotin consists of an imidazole ring fused to a tetrahydrothio-
FUNCTION phene ring with a valeric acid side chain. It has eight possible
Folic acid functions as a one-carbon (methylene, methenyl, stereoisomers in nature but only d-(+)-biotin is physiologically
methyl) donor and acceptor molecule in intermediary metabo- active (NRC, 2006). Biotin is unstable to oxidation and heat.
lism. Specific pathways include nucleotide biosynthesis, phos-
pholipid synthesis, amino acid metabolism, neurotransmitter FUNCTION
production and creatinine formation. In addition, vitamin B 12 Biotin is an essential cofactor for four different carboxylase
is closely paired with folate in the production of methionine reactions in mammals. These carboxylases have important
from homocysteine, which will be discussed later in this section. functions in the metabolism of lipids, glucose, some amino
acids and energy.
METABOLISM
Natural sources of folic acid undergo hydrolysis by the intes- METABOLISM
tinal enzyme γ-glutamyl hydrolase to form folylmonoglutamate, The majority of biotin in food sources is thought to be cova-
which is subsequently absorbed by enterocytes. Thus, the major lently bound to proteins. After ingestion, biotin must be
form of folic acid in blood is the monoglutamate form. After hydrolyzed from protein by the enzyme biotinidase in pancre-
target cells absorb folylmonoglutamate, additional glutamates atic juice before absorption in the intestine (Brody, 1994a;
are added to the tail, which trap the molecule within cells. Mock, 1996). After hydrolysis, free biotin is actively absorbed
Folic acid must be in the reduced form (i.e., dihydro or through a biotin transporter that requires both an intact ureide
tetrahydro) to participate in one-carbon metabolic reactions. group and a free carboxyl group on valeric acid (NRC, 2006).
The enzyme dihydrofolate reductase (DHFR) interconverts Avidin in raw egg white can tightly bind biotin and is resistant
dihydrofolates to tetrahydrofolates. Inhibition of this enzyme to intestinal proteolysis and heat treatment, making biotin
interferes with intermediary pathways that require reduced unavailable for absorption. After absorption from the intestine,
folates for coenzymes. C677T mutation in the methylenete- biotin is transported in the free form in the plasma to the
trahydrofolate reductase (MTHFR) gene also affects folate required tissues where it is linked to its target apoenzyme by the
metabolism and requirement (Golbahar et al, 2005). enzyme holocarboxylase synthetase. The kidneys eliminate
excess biotin. Increasing urinary excretion of 3-hydroxyisova-
REQUIREMENTS leric acid, an indicator of reduced activity of the biotin-depend-
The AAFCO (2007) recommended allowance for folic acid ent enzyme methylcrotonyl-CoA carboxylase, and decreasing
is 0.18 mg/kg DM for dogs and 0.8 mg/kg DM for cats for all biotin in urine are early and sensitive indicators of biotin defi-
lifestages, respectively. The NRC (2006) recommended ciency (Mock et al, 2002).
allowance for folic acid is 270 µg/kg DM for dogs and 750
µg/kg DM for cats regardless of lifestage. Table 6-5 lists REQUIREMENTS
AAFCO and NRC allowances for dogs and cats. Neither AAFCO (2007) nor NRC (2006) has a recommen-
dation for biotin for dogs. However, diets containing raw egg
DEFICIENCY AND TOXICITY white and/or antibiotics may need biotin supplementation.The
Folate deficiency is characterized by poor weight gain, mega- AAFCO (2007) biotin recommendation for cats is 0.07 mg/kg
loblastic anemia, anorexia, leukopenia, glossitis and decreased DM for all lifestages. The NRC (2006) recommended
immune function. In cats, folate deficiency is associated with allowance for biotin for cats is 75 µg/kg DM regardless of
hyperhomocysteinemia and greatly augmented urinary excre- lifestage. Table 6-5 lists AAFCO and NRC allowances for
tion of formiminoglutamic acid (Yu and Morris, 1998). Folate dogs and cats.
deficiency has been linked to the risk of neural tube defects in
people (Mitchell,2005).Folate levels in blood may be measured DEFICIENCY AND TOXICITY
to confirm a deficiency suggested by clinical signs. Table 6-5 Naturally occurring biotin deficiency is very rare in dogs and
lists plasma levels for healthy cats and dogs (Baker et al, 1986). cats (NRC, 2006). Feeding raw egg whites and administering
There have been no reported cases of folate toxicity. Neither oral antimicrobials are probably the two most common causes
NRC nor AAFCO has proposed a dietary maximum concen- of biotin deficiency. Raw egg whites contain the glycoprotein
tration for folic acid. avidin, which binds biotin rendering it unavailable for absorp-