Correct targeting of newly synthesized hydrolytic enzymes to the lysosomes requires which of the following modifications?

Correct targeting of newly synthesized hydrolytic enzymes to the lysosomes requires which of the following modifications?

(A) attachment of mannose-6-phosphate to the enzymes
(B) gamma-carboxylation of glutamate residues in the enzymes
© O-linkage of carbohydrate to the enzymes
(D) prenylation of the enzymes
(E) proteolytic activation following transport to the lysosome

Explanation:

Enzymes that are targeted to the lysosomes undergo a specific two-step modification in the Golgi complex. The first step in the modification involves the attachment of an alpha-Nacetylglucosamine 1-phosphate residue to the six position of a mannose residue on the high man-nose carbohydrate portion of lysosomal enzymes. The second step involves removal of theN-acetylglucosamine residue exposing the mannose-6-phosphate marker. The presence of mannose-6-phosphate is necessary for targeting lysosomal enzyme to the lysosomes and deficiencies in the enzyme responsible for the first reaction in the modification lead to severe developmental abnormalities. Carboxylation of glutamate residues (choice B) is necessary to the function of several enzymes of the coagulation cascades. Lysosomal enzymes are not modified by attachment of carbohydrate through O-linkage (choice C). Many membraneanchored proteins undergo lipid modification by prenylation (choice D) such as the protein product of the protooncogene RAS. Although many enzymes are activated by proteolytic processing (choice E), this is not required for targeting lysosomal enzymes to the lysosome.