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

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Chapter | 23 Vitamins
NH 2
NH 2
N
N
N
N
O
O
O
H 2 C
OH
P
O
O
OH
P
O
H 2 C
O
N
O
R
N
OH OH
OH OH
HO
P OH
HO O
H
X
H
X
R
H R C R’ R N
R C R’
H
H S
H 2 N O
H 2 N
O
H
Tryptophan
quinolinic acid
α-amino-β-carboxymuconic -ε-semialdehyde
nicotinic acid mononucleotide
nicotinic acid dinucleotide
NAD
NADP
Synthetic processes
Poly and mono ribosylation reactions;
cyclic ADP-ribose
Catabolic processes
Nicotinamide
N-methylnicotinamide
Excretory products
FIGURE 23-15 Niacin and NAD(P). Niacin can be derived from tryptophan degradation or the diet. In cells, niacin is eventually converted to
NAD(P). Most enzymes requiring NAD are oxidoreductases (dehydrogenases). The most common mechanisms involve the stereospecific abstraction
of a hydride ion (H:) from the substrate with subsequent transfer. NAD is usually associated with catabolic pathways, whereas NADP is utilized in
synthetic pathways. An additional and equally important function of NAD is its role as a substrate in poly- and monoribosylation reactions. Mono- and
polyribosylations are important to many cellular regulatory functions (e.g., DNA repair); cyclic-ADP ribose is important in calcium-related cell signaling
pathways.
that accounts for the rapid turnover of NAD in cells. Some
estimates suggest that as much as 40% to 60% of the NAD
in cells is involved in mono- or polyribosylation reactions.
NAD is also the substrate for cyclic ADP-ribose
(cADPR), which is a Ca2 mobilizing second messenger
found in various cell types, tissues, and organisms.
Receptor-mediated formation of cADPR involves ADPribosyl
cyclases located within the cytosol or in internal
membranes of cells. cADPR activates intracellular Ca2
release ( Jacobson et al., 1995 ).
c . Requirements and Pharmacology
Niacin is needed in amounts corresponding to 10 to 25 mg/kg
of diet. Depending on species, the conversion of tryptophan
to niacin produces about 1 mg of niacin for every 60 mg of
tryptophan degraded. Niacin (nicotinamide) is relatively
nontoxic, although nicotinic acid can cause vasodilatation
when consumed in excess of 100 mg per kilogram of diet.
Consequently, there are a number of therapeutic uses for
pharmacological doses of niacin-derived compounds, when
increased blood flow is desirable.