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Studies of the enzymatic oxidation of proline and pyrroline-5-carboxylate in mammalian mitochondria

Thesis/Dissertation ·
OSTI ID:6968977
The two-step oxidation of proline to glutamate in vivo is catalyzed unidirectionally by the enzymes proline oxidase (E.C. 1.5.99.8) and pyrroline-5-carboxylate (P5C) dehydrogenase (E.C. 1.5.1.12). Attempts were made to purify both proteins from rat liver. In the case of proline oxidase, an integral protein of the inner mitochondrial membrane, a number of detergents were used in efforts to solubilize active free enzyme. Detergent-treated fractions were subjected to gel permeation and other chromatographic procedures, and proline oxidase was found as part of a large particle which could not be purified. Accurate kinetic analysis of the enzyme using spectrophotometric techniques was difficult due to interference from assay components. A radiochemical assay was developed which directly measured the production of radiolabeled glutamate from P5C. The compounds were separated by cation-exchange chromatography. This assay was used to screen rat tissues for activity. Western blot analysis utilizing a polyclonal rabbit anti-rat antiserum suggests the two proteins may immunocrossreact. Kinetic analysis of these enzymes using semialdehydes and other aldehydes as substrates show a similar general pattern of substrate specificity, but the rate enzyme appears to be more specific for P5C. Aliphatic semialdehydes, closely analogous in structure to P5C, are commercially unavailable. A colorimetric assay was developed to accurately quantitate semialdehydes after synthesis. This assay is dependent upon oxidation of a covalent adduct of semialdehyde with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole.
Research Organization:
North Carolina Univ., Chapel Hill, NC (USA). Inst. of Statistics
OSTI ID:
6968977
Country of Publication:
United States
Language:
English