Question

2. (13 points) Fabry disease results from a defect in the a-galactosidase A enzyme which hydrolyzes specific glycolipids (Box 10-1). Answer the questions that follow. A. 17 points) Identify the substrate for a-galactosidase A and draw its full structure. B. (1 point) Indicate the location of enzymatic hydrolysis on your drawing. C. (1 point) Describe the function of the glycolipid identified in part A. D. (1 point) What cellular location would you normally find the molecule in part A? E. (3 points) Briefly describe how Fabry disease arises at the biochemical level.

Answer 1

Answers-

(A) Substrate of alpha-galactosidase are Sphingolipidoses, These are a class of lipid storage disorders relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy.

Sphingosine (C ) 18 'c-OH . Hydrolysis y site y SL Η Ι -N-C 2-0- fatty acid head group

(B) Hydrolysis site has been indicated in the figure.

(C) Function of Sphingolipidoses- Sphingolipidoses are lysosomal storage disorders in which enzymes of sphingolipid catabolism are absent. In these disorders, the sites of sphingolipid catabolism like lysosomes of phagocytes, histiocytes or macrophages in bone marrow, liver and spleen are affected.

(D) The cellular location of Sphingolipidosase are LYSOSOMES.

(E) Fabry Disease- The lack of alpha-galactosidase is what leads to Fabry disease. A deficiency of the enzyme alpha galactosidase A (a-GAL A, encoded by GLA) due to mutation causes a glycolipid known as globotriaosylceramide (abbreviated as Gb3, GL-3, or ceramide trihexoside) to accumulate within the blood vessels, other tissues, and organs. This accumulation leads to an impairment of their proper functions.

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