Kinetic Parameters of Thymidine Kinase and DNA Synthesis During Liver Regeneration: Role Ofthyroid Hormones

The role of thyroid hormones in DNA synthesis and in the activity of Thymidille kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a model for controlled cell division in rats having different thyroid status - euthyroid, hypothyroid and 3,3',5'-triiodo-L-thyronine (T))-heated hypothyroid. Partial hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three groups compared to their sham-operated counterparts. Hypothyroid liepatectomised animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid hepatectomised animals. A single subcutaneous close of 1'3 to hypothyroid shamoperated animals resulted in a significant increase (p<0.01) of DNA synthesis in the intact liver. 17tis was comparable to the level of DNA synthesis occurring in regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, "1'3 showed an additive effect on l)NA synthesis and this group exhibited maximum level of DNA synthesis (p<0.0I ). Studies of the kinetic parameters of TK show that the Michelis-Menten constant, (K111) of TK for thymidine was altered by the thyroid status. K11 increased significantly (p<0.01) in untreated hypothyroid animals when compared to the euthyroid rats. '13 treatment of hypothyroid animals reversed this effect and this group showed the lowest value for K111 (p<0.01). Thus our results indicate that thyroid hormones can influence DNA synthesis during liver regeneration and they may regulate the activity of enzymes such as 17rymidine kinase which are important for DNA synthesis and hence cell division.

Kinetic Studies of Purified malate Dehydrogenase in Liver of Streptozotocindiabetic Rats and the Effect of Leaf Extract of Aegle Marmelose (L.) Correa ex Roxb

The functional basis of diabetes-mellitus to a certain extent, can be elucidated by studying diabetes-induced changes in metabolic enzymes. Malate dehydrogenase (MDH), is an enzyme directly involved in glucose metabolism. The kinetic parameters of MDH and its purified cytosolic isozyme, S-MDH, have been studied in the liver of streptozotocin- diabetic rats; also the potential of the leaf extract of A. marmelose as an was investigated. The Km of the liver enzyme increased significantly, in both crude and purified preparations in the diabetic state when compared to Lhe respective controls. Insulin as well as leaf- •extract treatment of the diabetic rats brought about a reversal of K. values to near normal. Vmax of purified S-MDH was significantly higher in the diabetic state when compared to the control. Insulin and leaf extract treatment did not reverse this change. Since MDH is an important enzyme in glucose metabolism, the variation in its quantitative and qualitative nature may contribute to the pathological status of diabetes. The fact that leaf extract of A. marmelose was found to be as effective as insulin in restoration of blood glucose and body weight to normal levels, the use of A. marmelose as potential hypoglycemic agent is suggested.