Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Dyggve-Melchior-Clausen (DMC) syndrome includes short stature, dwarfism, mental retardation, and skeletal abnormalities especially in the spine and the extremities resembling the findings in the mucopolysaccharidoses. A particular abnormality is the "lace border" found on radiological examination of the iliac crest. The three original cases have been followed for 15--20 years and the course is characterized by increasing mental retardation and motor disability whereas the "lace border" is less pronounced than before. A survey of 17 other cases is given and similarities and differencies to the mucopolysaccharidoses are pointed out. Patients with the DMC syndrome have been suggested to be deficient in an enzyme cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients, an abnormal excretion of urinary AMP's of which some were undersulfated and some were oversulfated. Lysosomal acid proteinase, i.e., cathepsin D and neutral proteinases: elastase and cathepsin G were found to be normal in DMC patients. However, alfa2-macroglobulin in serum was raised. This increase may cause an inhibition of the neutral proteinases. An increased level of chondroitin sulfate N-acetylgalactosamine-6-sulfate-sulfatase and decreased enzymic levels of aryl sulphatase A and B (assayed with p-nitrocatecholsulfate as a substrate) were found in leucocytes of DMC patients. Metabolic studies have revealed an unbalanced incorporation of glycoprotein AMP-precursors in DMC lymphocytes. All in all the data suggests the DMC syndrome to be an inborn error of glycoprotein-AMP-metabolism.
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PMID:The Dyggve-Melchior-Clausen (DMC) syndrome. A 15 year follow-up and a survey of the present clinical and chemical findings. 57 40

Glycosylation plays an important role in glycoprotein traffic. Our previous work has shown that long term treatment of mucus-secreting HT-29 cells with GalNAc-alpha-O-benzyl reversibly inhibits sialylation and causes the accumulation of apical glycoproteins in cytoplasmic vesicles. We have analyzed at the biochemical level the effects of GalNAc-alpha-O-benzyl on glycoprotein processing. Both apical and basolateral membrane glycoproteins were sialylated, but GalNAc-alpha-O-benzyl selectively inhibited the sialylation of apical glycoproteins. In addition, lysosomal alpha-glucosidase, which is partially targeted to the apical membrane, was abnormally processed leading to the accumulation of an immature molecular species. Several findings support the conclusion that accumulation of this protein occurs in a post-trans-Golgi network (TGN) compartment: 1) it is partially sialylated; 2) it does not occur when glycoprotein exit from the TGN is blocked at 20 degrees C; 3) upon Triton X-114 partition, it distributes to the aqueous phase, a characteristic that is acquired in a post-TGN compartment; and 4) its appearance is inhibited when cells are cultured in the presence of NH(4)Cl. The processing of cathepsin D was also found to be affected by GalNAc-alpha-O-benzyl treatment. In conclusion, GalNAc-alpha-O-benzyl selectively inhibits sialylation of apical glycoproteins and perturbs lysosomal enzyme processing; these effects occur in a post-TGN acidic compartment and are reminiscent of the alterations found in sialic acid storage diseases.
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PMID:GalNAc-alpha -O-benzyl inhibits sialylation of de Novo synthesized apical but not basolateral sialoglycoproteins and blocks lysosomal enzyme processing in a post-trans-Golgi network compartment. 1075 88