Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

• Published in: Biochemistry (Easton) Vol. 28; no. 5; pp. 2027 - 2034
• Main Authors: Tropea, Joseph E, Molyneux, Russell J, Kaushal, G. P, Pan, Y. T, Mitchell, Michael, Elbein, Alan D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.03.1989
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; 550602 - Medicine- External Radiation in Diagnostics- (1980-); ALKALOIDS; Animals; BARYONS; CARBOHYDRATES; Carbohydrates - biosynthesis; Cells, Cultured; COHERENT SCATTERING; DIFFRACTION; ELEMENTARY PARTICLES; ENZYME ACTIVITY; ENZYMES; FERMIONS; Glucan 1,4-alpha-Glucosidase - antagonists & inhibitors; GLUCOPROTEINS; Glucose - metabolism; GLUCOSIDASE; Glucosidases - antagonists & inhibitors; GLYCOPROTEINS; Glycoproteins - metabolism; Glycoside Hydrolases - antagonists & inhibitors; GLYCOSYL HYDROLASES; HADRONS; HYDROLASES; In Vitro Techniques; Indolizines; INHIBITION; MAGNETIC RESONANCE; MOLECULAR STRUCTURE; NUCLEAR MAGNETIC RESONANCE; NUCLEONS; O-GLYCOSYL HYDROLASES; ORGANIC COMPOUNDS; PLANTS; Plants - analysis; Protein Biosynthesis; PROTEINS; PROTONS; Pyrrolizidine Alkaloids - pharmacology; RADIOLOGY AND NUCLEAR MEDICINE; RESONANCE; SACCHARIDES; SCATTERING; SEEDS; TREES; X-RAY DIFFRACTION
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00431a010

Australine [(1R,2R,3R,7S,7aR)-3-(hydroxymethyl)-1,2,7-trihydroxypyrrolizid ine] is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis [Molyneux et al. (1988) J. Nat. Prod. (in press)]. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, we tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the alpha-glucosidase amyloglucosidase (50% inhibition at 5.8 microM), but it did not inhibit beta-glucosidase, alpha- or beta-mannosidase, or alpha- or beta-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc3Man7-9(GlcNAc)2-oligosaccharides.