13 Glycolysis Regulation

13 Glycolysis Regulation - Biochemistry Education BIOC 423:...

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B iochemis±ry ²E duca±ion Department±of±²iochemistry±&±Molecular±²iology University±of±New±Mexico BIOC 423± Int²oducto²y Biochemist²y Regulation of glycolysis, fates of pyruvate OBJECTIVES Know which reactions in the glycolytic pathway are not readily reversible and why. Know which reactions in the glycolytic pathway are regulated, which molecules regulate these reactions, and understand how these regulators integrate the upstream reactions of glycolysis with the downstream demands for the products of glycolysis Understand the role of fructose 2,6 biphosphate in the regulation of liver phosphfructokinase. Understand what is meant by the term "first committed step in a pathway". Know the physiological significance of the alternate fates of pyruvate (acetyl CoA, ethanol, lactate). OUTLINE ATP Regulation of glycolysis in muscle Hexokinase PFK-1 Pyruvate kinase A problem unique to the liver: processing glucose in the presence of elevated ATP Glucokinase vs. hexokinase Insulin and PFK II Glucagon and PFK II Activation of pyruvate kinase Solutions to the NAD + Problem Lactate dehydrogenase Pyruvate decarboxylase General Strategies of Regulation End product inhibition of committed steps Regulation at branch points
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LECTURE As a central pathway for both energy production and biosynthesis, glycolysis must receive feedback from both pathways. Moreover, control of the enzymes in glycolysis must take into consideration the alternate routes that glucose 6- phosphate can take in the cell. As indicated in the figure below, glucose 6- phosphate is a major connection between several different pathways. If we were to focus our regulatory strategies on the first reaction of glycolysis that we studied, hexokinase, we would inhibit all of the processes shown in blue because the important metabolite, glucose 6-phosphate would not be produced. Consequently, the regulation that produces glucose 6-phosphate must be independent of the other regulatory points of the pathway. Glucose 6-phosphate Py±uvate Pentose Phosphate Pathway Glycogen Glucose Complex Ca±bohyd±ates In general, enzymes that catalyze irreversible reactions are major regulatory points. There are three such enzymes in glycolysis: hexokinase, phosphofructokinase I, and pyruvate kinase. All three enzymes are important regulatory points of glycolysis Regulation of Glycolysis in Muscle Hexokinase regulation As stated above, we do not want to focus the total control of glycolysis on the enzyme hexokinase. However, we still need to control the enzyme.
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Hexokinase has a very low Km (high affinity) for glucose which is lower than normal blood glucose concentrations. This means that unless the enzyme is inhibited, any glucose entering the cell will be trapped as glucose 6- phosphate. If the product, glucose 6-phosphate is not being consumed then we will trap large amounts of glucose 6-phosphate in the cell, which will subsequently bring water into the cell because of the osmotic activity of small molecules. In other words we do not want to make more glucose 6-phosphate
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13 Glycolysis Regulation - Biochemistry Education BIOC 423:...

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