The unsolved mystery of human ADP-dependent glucokinase : a thesis presented in partial fulfilment of the requirement for the degree of Master of Science in Biochemistry at Massey University, Palmerston North, New Zealand
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Date
2010
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Massey University
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Abstract
Human ADP-dependent glucokinase (hADP-GK) is the most recently discovered glycolytic enzyme that has been shown experimentally to phosphorylate glucose to glucose-6-phosphate. This reaction is catalysed using ADP as the phosphoryl donor, which is uniquely different from the traditional ATP-dependent hexokinase type I-IV enzymes that were initially shown to carry out the first step of glycolysis.
The functional role of hADP-GK within the cell and the significance of utilizing an ADP-dependent glucokinase have yet to be elucidated experimentally. It has been hypothesised that the unique characteristic of ADP utilisation may provide cellular advantages during times of limited energy and oxygen (hypoxia), as ATP is able to be conserved during anaerobic glycolysis. Cellular survival and sustainability may be increased during disease states as ADP is invested into the first step of glycolysis instead of ATP. AMP is also produced during this reaction, and may activate AMP-activated protein kinase (AMPK), an energy sensor within the cell, which may regulate energy metabolism during times of low energy and/or hypoxia.
Prior to this research no experimental work had been carried out on the regulation of hADP-GK at the transcriptional level. The main objectives of this project were to investigate the effect of glucose concentration on the expression of hADP-GK at the transcriptional level, and to investigate the promoter and potential transcription factors responsible for promoter activity. The cellular localisation of hADP-GK was also briefly investigated through microscopy. This experimental work has opened up a new path for future research, and therefore the continuation of this project would be important in understanding the role of hADP-GK.
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Human ADP-dependent glucokinase, Enzymes, Biochemistry