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Gluconeogenesis

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Introduction

  • Reversal of glycolysis

    • recall that glycolysis has 3 "irreversible" steps, meaning the same enzyme does not catalyze both directions of the reaction​

    1. PEP -> pyruvate​

    2. F6P -> F1,6BP

    3. Glucose -> G6P

  • key to gluconeogenesis

    • otherwise the pathway would reverse if pushed from the other end - would be wasteful​

Glycolysis: Step 10

Gluconeogenesis: cannot bypass in just one single step

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Pyruvate Carboxylase Reaction

  • In mitochondria

  • biotin involved in carboxylation

  • this reaction replenishes TCA cycle intermediates 

    • OAA is needed to run acetylCoA via TCA cycle​

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PEP Carboxykinase (PEPCK)Reaction

  • In liver

  • PEPCK is expressed in both mitochondria and cytoplasm

  • when in mitochondria, PEP is transported to cytoplasm and continues with gluconeogensis

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Glycolysis: Step 3

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Glycolysis: Step 1

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Overview

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Gluconeogenesis involves a bog input of ATP

  • going uphill thermodynamically​

    • -3 ATP per cycle​

    • -6 ATP per glucose

  • gluconeogenesis converts 2 pyruvate to 1 glucose​

    • 2 pyruvate + 4 ATP + 2 GTP + 2NADH + 6H2O --> glucose + 4 ADP + 2 GDP + 6Pi + 2NAD + 2H​

  • glycolysis

    • glucose + 2 ADP + 2 NAD+ --> 2 pyruvate + 2 ATP + 2 NADH + 2H​

  • reflects the difference of the energy required to drive an overall energetically unfavorable reaction

Gluconeogenesis - Other Substrates

Lactate as a precursor

  • many cells oxidize glucose anaerobically which produces lactate

    • muscle​

    • GI

    • RBC (no mito)

    • lens of eye (no mito)

  • lactate as a substrate​​

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Glycerol as a precursor

  • released from ​​adipose into blood when TG is broken down

  • goes to liver

  • enters glycolysis or gluconeogenesis as a 3 carbon unit

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Amino Acids as precursors

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©2023 by Syracuse University Dr.Margaret Voss

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