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

IV. Water-Soluble Vitamins
717
H 2 N
N
N
OH
N
C
S
CH 3
CO 2
H 3 C
N
S
H
CO
(a)
R'
O O
C
O R
-ketoacid
S
R"
O
HO
R
R'
O
N
C
S
R"
R'
N
HO
C
C
S
R
R"
CoA
N H O
Pyruvate, RCH 3
-ketoglutarate, RCH 2 CH 2 COO
(b)
Resonance
stabilized
CoA
S
O
CH 3 C
Acetyl CoA
from pyruvate
S
O
C
C
O
Succinyl CoA
from -ketoglutarate
Transfer of decarboxylation
product to coenzyme A
(several steps)
R'
N
HO
C
C
S
R
R"
(c)
HO
H
CH O
2 OH
O
O
H O
H H OH
transketolase
OH H OH
H OH
2
2
CH 2 PO 3
CH 2 PO 2
3 CH2 PO 3
Xylulose
5-phosphate
Erythrose
4-phosphate
Glycoraldehyde
3-phosphate
HO
H
H
CH 2 OH
O
H
OH
OH
2
CH 2 PO 3
Fructose
6-phosphate
FIGURE 23-17 Thiamin. The structure of thiamine (a) is shown in its vitamin form. Along with magnesium, thiamin as thiamin pyrophosphate is
designed to interact with C O moieties to initiate active aldehyde transfer reactions. One example is the decarboxylation of α -keto acids or transketolase
reactions (b). Thiamin also facilitates the transformation of “ ketols ” (ketose phosphates) in the pentose phosphate pathway (c).
are two general types of reactions wherein TPP functions.
TPP is a coenzyme for active aldehyde transfer reactions,
most often coordinated with magnesium. One example is
the decarboxylation of α -keto acids. This type of reaction
is called the transketolase reaction. TPP also facilitates the
transformation of “ ketols ” (ketose phosphates) in the pentose
phosphate pathway. The importance of these reactions
cannot be overstated. The first type of reaction, decarboxylation
of “ keto acids, is essential to the flux of substrates
through the TCA cycle (i.e., the conversion of pyruvic acid
to acetyl CoA and the conversion of α-ketoglutarate to
succinyl CoA). In the pentose phosphate pathway, NADP
is also reduced to NADPH, an essential reducing agent for
synthetic reactions (see niacin ) . Consequently, with a deficiency
of thiamin there is impaired metabolism of carbohydrates,
because of defective TCA cycle regulation. Further,
if there are perturbations in the pentose phosphate-related
carbohydrates pathway, there can be decreased production
of NADPH, which may impact other synthetic processes,
such as fatty acid biosynthesis.
Another function that may be ascribed to thiamin
occurs in brain and neural tissue. In the brain, TPPP is
proposed to be involved in sodium-gating processes (i.e.,
the flux of sodium ions, across neuronal cell membranes)
( Bettendorff, 1996 ). This aspect of thiamin metabolism
may be related to the psychosis and impairment of neuromuscular
control that is observed in thiamin deficiency.
c . Requirements
Thiamin status should be routinely considered in disease
assessment, because a number of factors influence thiamin
availability and may induce deficiency. Thiamin is heat
and alkali unstable, so extensive destruction of thiamin can