A series of four experiments was undertaken to determine both the quantitative and qualitative effects of magnesium deprivation on the urinary glycoproteins of adult and grow.ing rats. The glycoproteins were to be isolated in 0.58 M Na.Cl, the isolation technique for Tamm-Horsfall glycoprotein. Quantitative excretion was measured as ɣ hexose/rat/day. Qualitative analyses were reported as percent of dry weight of material isolated. A glycoprotein-containing material precipitated spontaneously from the urine before addition of NaCl. The dry weight ratio of spontaneously precipitating material (Fraction I) to salt-precipitable material (Fraction II) was 16 to one in normal animals, 3.4 to one in depleted animals. The hexose to amino acid to uronic acids ratio was the same for both fractions in both groups. No hexosamines were found in either fraction. The ash content was lower in Fraction I for deficient animals, but higher in Fraction II for deficient animals, when compared to control animals. Increased phosphate binding by Fraction II from deficient animals was indicated. A slight rise in total glycoprotein excreted daily was shown in animals fed a magnesium deficient diet, but not until after the first week, when irreversible kidney damage is initiated. Control animals whose weight ga:m was restricted to 32% 0£ normal excreted less of Fraction I per day. Amino acid patterns of both fractions from all groups were similar, but differed from those reported for human and sheep Tamm-Horsfall glycoprotein. All depleted animals showed a significant (p> 0.01} increase in kidney calcium content, and one group showed a significant (p> 0.01) decrease in kidney magnesium content at five weeks. / M.S.

This thesis concentrates on understanding how individual nonspecific DNA–protein contacts are used in the excision mechanism of the human DNA repair enzyme, alkyladenine DNA glycosylase (AAG). Initially, studies focus on understanding the structure and magnitude of these fundamentally different DNA–protein stacking and T-shaped interactions to be applied to the active site of AAG. High-level ab initio techniques revealed fundamental knowledge about the structure and magnitude of these distinctly different – and +– contacts between (one or two) conjugated amino acid(s) and one nucleobase. Additionally, the mechanism used by AAG to excise (neutral and cationic) damaged nucleotides was investigated using a hybrid ONIOM approach. Reaction potential energy surfaces reveal that AAG prefers to excise both neutral and cationic substrates through a concerted mechanism, yet the nonspecific contacts present in the active site are only catalytic for the cleavage of the neutral substrates. / xvi, 195 leaves : ill. (some col.) ; 29 cm + 1 CD-ROM