1991 Fiscal Year Final Research Report Summary
Biochemical and molecular genetical studies on a new glycoprotein storage disorder
| Project/Area Number |
02671007
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | University of Shizuoka |
|---|
Principal Investigator |
HIRABAYASHI Yoshio University Shizuoka, Department of Biochemistry, Assistant Professor, 薬学部, 講師 (90106435)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANZAKI Tamotsu Nagoya City University School of Medicine, Department of Dermatology, Associate, 医学部, 助教授 (80118801)
|
|---|
| Project Period (FY) |
1990 – 1991
|
| Keywords | Kanzaki disease / glycoprotein / Schindler disease / O-linked type oligosaccharide / alpha-N-acetylgalactosaminidase |
|---|
| Research Abstract |
We found a new case with abnormality in the catabolism of 0-linked oligo saccharides of glycoprotein. The patient has a typical syndrome accompanied by Fabry's disease. On direct analysis of the patient urine, there were found four major spots but not in normal urine samples. Structural analysis by NMR and FAB-MS revealed that the accumulated compounds to be O-linked oligosaccharides bound to either peptides or single amino acids. Based on assessment of exo- and endo-glycosidase activities, the patient was shown to be caused by a deficiency of alpha-N-acetylgalactosaminidase. In collaboration with Dr. Desnick, the disease was caused by C - T transition of the enzyme gene.
Two members of a consanguineous Japanese family with angiokeratoma were found. Biochemical studies showed elevated excretion of urinary sialooligosaccharides and decreased activity of aspartylglycosylamine amidohydrolase. Ours are the first Japanese patients diagnosed as aspartylglycosaminuria.
To analyze the accumulated compound in the patient urine from the new type of the diseases -, highly sensitive method using HPLC with PAD detector has been developed. Using the analytical system, for example, O-linked type oligosaccharides can be detected and determined with few ul of urine sample from Kanzaki disease patient.
|
