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

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Chapter | 23 Vitamins
Carnitine
Reverses the
inhibition
by CoA
CoA
Inhibitor
Coenzyme A synthesis
Pantothenate
ATP
Pantothenate Kinase
ADP
4-Phosphopantothenate
ATP
4- Phosphopantothenoylcysteine Synthetase
ADP P i
4-Phosphopantothenoylcysteine
4-Phosphopantothenoylcysteine Decarboxylase
CO 2
PP i
3,5-ADP
4-Phosphopantetheine
ATP
Dephosphocoenzyme A
ATP
ADP
Coenzyme A (CoA or CoASH)
Dephosphocoenzyme A Kinase
FIGURE 23-19 Pantothenic acid and coenzyme A. The most important control step in CoA synthesis is the phosphorylation of pantothenic acid to
4 -phosphopantothenic acid by pantothenic acid kinase. There is feedback regulation from CoA and carnitine reverses that inhibition. Most cells are
able to conserve pantothenic acid by reutilizing 4 -phosphopantothenic acid.
Elvehjem, Jukes, and others demonstrated pantothenic acid
to be essential for animals. Pantothenic acid is a component
of coenzyme A ( Fig. 23-19 ). Pantothenic acid (as a
part of phosphopantetheine) is also present at the active
site of acyl carrier protein (ACP), a component of the fatty
acid synthesis complex. Both forms are present in foods.
Consequently, absorbed pantothenic acid must first be
released from coenzyme A and ACP, steps that involve the
actions of peptidases and nucleosidases.
b . Absorption and Regulation
Intestinal phosphatases and nucleosidases are capable
of very efficient hydrolysis of coenzyme A so that near
quantitative release of pantothenic acid occurs as a normal
part of digestion. In rats, pantothenic acid was initially
found to be absorbed in all sections of the small
intestine by simple diffusion ( Rucker and Bauerly, 2007 ).
However, subsequent work in rats and chicks indicated
that at low concentrations, the vitamin is absorbed by a
saturable, sodium-dependent transport mechanism ( Rucker
and Bauerly, 2007 ; Said, 2004 ). Further, the overall km
for pantothenic acid intestinal uptake is 10 to 20 μ m. At
an intake of 20/30mg/kg diet as coenzyme A or pantetheine
, a concentration typical of many foodstuffs, the
pantothenic acid concentration in luminal fluid would be
1 to 2 μ m. At this concentration, pantothenic acid does
not saturate the transport system, and should be efficiently
and actively absorbed. Pantothenic acid shares a common
membrane transport system in the small intestine with
another vitamin, biotin ( Said, 2004 ). Following uptake,
the maintenance of pantothenic acid cellular concentration
depends on its incorporation into cellular CoASH and pantetheine.
The most important control step in this process
is the phosphorylation of pantothenic acid to 4 -phosphopantothenic
acid by pantothenic acid kinase. At least four
known enzyme isoforms serve as pantothenic acid kinases.
They possess a broad pH optimum (between pH 6 and 9).
The K m for pantothenic acid in the liver enzyme of most
animals is 20 μ m. Mg-ATP is the nucleotide substrate for
the phosphorylation reaction.
c . Metabolism Functions and Requirements
CoA is the principal moiety for the vectorial transport of
acyl and acetyl groups in synthetic and catabolic reactions,
and a deficiency is characterized by impaired acetyl and
acyl metabolism. The ability to utilize fatty acids as fuels
is compromised. There is also an increased production of
short chain fatty acids and ketone bodies, which can lead
to severe metabolic acidosis.
CoA is involved in a broad array of acetyl and acyl
transfer reactions, which also includes carbohydrates and
amino acids as cosubstrates, as well as processes related
primarily to lipid oxidative metabolism and catabolism,
whereas ACP is involved in mostly synthetic reactions
involving primarily lipids and possibly amino acids. Protein
acetylations and acylations are also key functions catalyzed
with CoA as a cosubstrate in reactions. Aminoterminal
acetylations occur cotranslationally and posttranslationally