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iii CHAPTER 1: GENERAL INTRODUCTION 1 Hexokinase and its isozymes 1 Structure of Hexokinase and G6P inhibition 4 Mitochondrial Binding of hexokinase 8 Hypotheis 10 Thesis Organization 11 References 11 CHAPTER 2: SINGLE-RESIDUE DETERMINANTS IN THE BINDING OF RECOMBINANT HUMAN BRAIN HEXOKINASE TO THE MITOCHONDRION 18 Abstract 18 Introduction 19 Experimental Procedures 22 Results 25 Discussion 37 References 41 CHAPTER 3: GENERAL CONCLUSIONS 46 ACKNOWLEDGMENT 47

Single Residue Determinants in the Binding of Recombinant Human Brain Hexokinase to the Mitochondrion