Qxalic acid, the simplest form of a dicarboxylic acid, is a common constituent of living organIsms, often deposited in tissues in the form of an insoluble calcium salt. in higher animals including humans, this process manifests itself most dramatically as urolithiasis or stone disease. Plants and fungi also accumulate calcium oxalate in distinctive crystalline forms that imply a highly regulated process of deposition. Although numerous attempts have been made to pinpoint the carbon source of the oxalic acid required for crystal formation in animals, little substantive progress has resulted from such efforts. The plant/fungus paradigm, through study of oxalic acid synthesis as it occurs during L- ascorbic acid metabolism (plants) or an analogous process involving D- erythroascorbic acid (fungi), provides an experimental approach to oxalic acid formation not available in the animal model. The objective of this proposal is to establish the process of ascorbate-linked oxalic acid synthesis in well-studied, easily-cultured plant models (Lemna minor L., Lemnaceae and Pistia stratiotes L, Araceae) and a corresponding fungal model (Sclerotinia sclerotiorum (Lib.) de Bary, ATCC 18687). L. minor and P. stratiotes demonstrate internal secretion and sequestration of oxalate while S. sclerotiorum actively secretes oxalic acid.
Specific aims i nclude the preparation of generally- and specifically-radiolabeled ascorbate precursors and ascorbates in order to trace the pathway of oxalic acid synthesis in the models, characterization of intermediates (specifically one unknown D-erythroascorbic acid-like compound that has already been isolated from S. sclerotiorum), isolation and purification of cell-free activities responsible for ascorbate cleavage and oxalate formation, and elucidation of events associated with oxalic acid synthesis and calcium oxalate deposition in the chosen models. information gained in this study can be applied to biomedical concerns involving oxalate production, deposition, and excretion in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045248-03
Application #
2016531
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1994-09-30
Project End
1998-08-31
Budget Start
1996-09-17
Budget End
1998-08-31
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Washington State University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164