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

II. Lysosomal Storage Diseases (LSDs)
733
O
COOH
O
H 2 COH
O
O
COOH
O
O
H 2 CO
S
O
O
COOH
O
O
etc
-L-iduronidase
2
N
S
NAc
H 2 COH
O
O
COOH
O
O
H 2 CO
S
O
O
COOH
O
O
etc
N
S
3
NAc
Heparan N-sulfatase
H 2 COH
O
O
COOH
O
O
H 2 CO
S
O
O
COOH
O
O
etc
Acetyl
CoA
NH 2
4
NAc
acetyl transferase
H 2 COH
O
O
COOH
O
O
H 2 CO
S
O
O
COOH
O
O
etc
NAc
NAc
-N-acetyl
glucosaminidase
5
COOH
O
O
H 2 CO
S
O
O
COOH
O
O
etc
-glucuronidase
6
NAc
N-acetyl
glucosamine
6-sulfatase
H 2 CO
S
O
NAc
O
COOH
O
FIGURE 24-2 The stepwise degradation of the glycosaminoglycan dermatan sulfate by a series of lysosomal
enzymes, all of which have been determined to be deficient in activity in domestic animals. From Neufeld and
Muenzer (1995) , with permission.
O
etc
genetic abnormalities result in the reduction or elimination
of the catalytic activity of the particular enzyme. This, in
turn, results in the accumulation within the lysosome of the
substrate of that enzyme ( Fig. 24-3 ), hence the name LSD.
In many LSDs, the reduction in the amount of product
of the metabolic pathway does not appear to produce disease.
However, the storage of cholesterol in Niemann-Pick
type C disease may result in a downstream deficiency
SUBSTRATE
LYSOSOMAL
ENZYME
PRODUCT
L M N O
METABOLIC
BLOCK
FIGURE 24-3 The reduction in catalytic activity of the enzyme, which
converts M to N, results in the accumulation of M within the lysosome.