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Biochemistry Lecture 11. Gluconeogenesis Metab 1 AB Metab 2 XY -Metabolic Pathways are Irreversible G between the 1st & last metabolite is large &

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Presentation on theme: "Biochemistry Lecture 11. Gluconeogenesis Metab 1 AB Metab 2 XY -Metabolic Pathways are Irreversible G between the 1st & last metabolite is large &"— Presentation transcript:

1 Biochemistry Lecture 11

2 Gluconeogenesis

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4 Metab 1 AB Metab 2 XY -Metabolic Pathways are Irreversible G between the 1st & last metabolite is large & neg. - If 2 metabolites are interconvertible (metab 1 metab 2), the path from Metab 1 Metab 2 must be different from that of Metab 2 Metab 1

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7 1.Carboxylation of pyruvate to oxaloacetate 2.Transport of oxaloacetate out of mitochondria mitocytoOxaloacetate Malate NADH + H + NAD + Malate Oxaloacetate NADH + H + NAD + Inner mito. Memb. A. Circumventing Pyruvate Kinase - Conversion of Pyruvate to Phosphoenolpyruvate 3. PEP Carboxykinase: decarboxylates and adds phosphate

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11 Dephosphorylation is not phosphorylation in reverse! Reverse Phosphorylation of ADP by F1,6 BP to generate F6P (and ATP) would be steeply uphill: F1,6 BP + ADP F6P + ATP G° = +3.4 kcal/mol Instead, dephosphorylation is carried out: F1,6 BP + H 2 O F6P + PO 4 G° = -3.9 kcal/mol Reverse Phosphorylation would be mediated by PFK Dephosphorylation is mediated by F1,6BPase B. Circumventing PFK – dephosphorylation of F1,6BP

12 C. Circumventing Hexokinase – dephosphorylation of G6P Mediated by G6Pase G6Pase is present only in liver and kidney Hence, these are the only tissues that can synthesize and secrete glucose into the blood

13 The Gluconeogenic Response is Activated Largely by the State of Feeding/Fasting Glycogen Glucose Pyruvate Acetyl CoA Blood Glucose Alanine FAs Blood Glucose

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15 The Cory Cycle

16 Gluconeogenesis & Glycolysis can Occur at the Same Time in Different Organs IN LIVER Glucose IN MUSCLE BLOODBLOOD Pyruvate Lactate Alanine GlycolysisGluconeogen. RED BLOOD CELLS Glucose Pyruvate Lactate Alanine *** The main substrate here is LACTATE***

17 Regulation of Metabolism

18 Overview of Energy Metabolism FATS POLYSACCHARIDES PROTEINS Fatty Acids, Glucose and Amino Acids Glycerol other sugars Stage I Digestion Acetyl CoA Stage II Anaerobic TCA cycle CO 2 CoA e- ADP ATP O2O2 Oxidative Phosphorylation Stage III Aerobic

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20 Principles of Regulation The flow of metabolites through the pathways is regulated to maintain homeostasis Sometimes, the levels of required metabolites must be altered very rapidly –Need to increase the capacity of glycolysis during the action –Need to reduce the capacity of glycolysis after the action –Need to increases the capacity of gluconeogenesis after successful action

21 Rates of a Biochemical Reaction Rates of a biochemical reaction depend on many factors Concentration of reactants Activity of the catalyst –Concentration of the enzyme –Intrinsic activity of the enzyme Concentrations of effectors –Allosteric regulators –Competing substrates –pH, ionic environment Temperature

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23 Reactions Far From Equilibrium are Common Points of Regulation

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25 Hexokinase Isozymes are different enzymes that catalyze the same reaction They typically share similar sequences Their regulation is often different

26 P eg. G6P is structurally similar to glucose, and competes with glucose for active site of hexokinase

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29 AMP ATP F6P Active site Allosteric site PFK

30 Fructose-2,6-bisphosphate

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35 Two Alternative Fates for Pyruvate Pyruvate can be a source of new glucose –Store energy as glycogen –Generate NADPH via pentose phosphate pathway Pyruvate can be a source of acetyl-CoA –Store energy as body fat –Make ATP via citric acid cycle Acetyl-CoA stimulates glucose synthesis by activating pyruvate carboxylase

36 Pancreas Glucagon Liver Glycogen Glucose F6P F1,6BP Pyruvate PK F2,6BP PFK Glucose (Blood) Brain Epinephrine Adrenal Medulla Glucose Muscle Glycogen F6PF2,6BP PFK F1,6BP Pyruvate PK


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