Gluconeogenesis vs. Glycolysis

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  • Created by: Tooba
  • Created on: 19-04-13 21:48

Introduction

Gluconeogenesis = process which synthesises glycose from pyruvate (comes from noncarbs like lactate, amino acids and glycerol)

Glycolysis = breakdown of glucose to pyruvate to generate ATP anaerobically

Both pathways have some common reactions, but aren't exact opposites (due to irreversible steps of glycolysis-bypassed in gluconeogenesis)

WHY DO WE USE THEM???

2 x molecule

Irreverible reaction

Step joining/cleaving 2 molecules

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Overview of gluconeogenesis

Pyruvate --> Oxaloacetate (converted via ATP in mitochondria)

Oxaloacetate --> Phosphoenolpyruvate (decarboxylated/phosphorylated-GTP in cytosol)

PEP --> 2-phosphoglycerate (hydrated)

2-PG --> 3-phosphoglycerate (isomerised)

3-PG --> 1, 3-bisphosphoglycerate (phosphorylated)

1, 3-BPG --> Glyceraldehyde-3-phosphate + orthophosphate (cleaved)

GA-3-P --> Dihydroxyacetone phosphate (readily interconverts)

GA-3-P + DHAP --> Fructose-1, 6-bisphosphate (joined)

F-1, 6-BP --> Fructose-6-phosphate (dephosphorylated)

F-6-P --> Glucose-6-phosphate (easily converted) * Free glucose easily diffuses in/out

G-6-P --> Glucose (dephosphorylated in liver and kidney ER)

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Overview of glycolysis

Glucose --> Glucose-6-phosphate (phosphorylated)

G-6-P --> Fructose-6-phosphate (isomerised)

F-6-P --> Fructose 1, 6-bisphosphate (phosphorylated)

F-1, 6-BP --> Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate (cleaved)

DHAP --> GA-3-P (isomerises)

GA-3-P + Orthophosphate --> 1, 3-bisphosphoglycerate (joined)

1, 3-BPG --> 3-phosphoglycerate (dephosphorylated)

3-PG --> 2-phosphoglycerate (isomerised)

2-PG --> Phosphoenolpyruvate (dehydrated)

PEP --> Pyruvate (converted)

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Enzymes involved

Pyruvate decarboxylase ||| Pyruvate kinase

PEP carboxykinase ||| ---

Enolase ||| Enolase

PG mutase ||| PG mutase

PG kinase ||| PG kinase

GA-3-P dehydrogenase ||| GA-3-P dehydrogenase

Triose phosphate isomerase ||| Triose phosphate isomerase

Aldose ||| Aldose 

F-1, 6-BPase ||| Phosphofructokinase

Phosphoglucose isomerase ||| Phosphoglucose isomerase

Glucose-6-phosphatase ||| Hexokinase

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Energy considerations

Glucose --> G-6-P; Hexokinase

F-6-P --> F-1, 6-BP; Phosphofructokinase

PEP --> Pyruvate; Pyruvate kinase

Have large, -ve delta G, so eqm lies to pyruvate formation side, so enzymes differ:

G-6-P --> Glucose; Glucose-6-phosphatase

F-1, 6-BP --> F-6-P; Fructose-1, 6-bisphosphatase

Pyruvate --> Oxaloacetate; Pyurvate carboxylase

Oxaloacetate --> Malate --> Oxaloacetate (moves from mitochondria to cytoplasm)

Oxaloacetate --> PEP; PEP carboxykinase

*Reversal of glycolysis = +84kJ/mol, but gluconeogenesis = -48kJ/mol:

*Hydrolysis of 4NTPs (2ATP + 2GTP) coupled to make unfavourable process, favourable.

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Reciprocal regulation

Glycolysis dependent on [glucose], gluconeogenesis depends on [glucose precursors]

Cell requires energy --> glycolysis predominates, surplus of energy --> gluconeogenesis

Reciprocal regulation = pathways controlled so one inactive while other is highly active

Rate and direction of both processes controlled at the points where they differ, because backwards and forwards reactions can be independently regulated

Biosynthetic and degradative pathways differ in 1 reaction min. so both thermodynamically favourable under similar physiological conditions (same steps in both processes near eqm under cellular conditions, so when 1 process is favoured, reactions take place in its direction)

Avoids futile cycle where 2ATP and 2GTP wastefully hydrolysed

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Mechanisms of regulation

1. F-6-P <--> F-1, 6-BP

High AMP (energy needed): PFK stimulated and F-1, 6-BPase inhibited

High ATP + citrate (high energy charge): inhibit PFK and citrate activates F-1, 6-BPase

2. PEP <--> Pyruvate

High ADP (low energy status): Pyruvate carboxylase + PEP carboxykinase inhibited

High acetyl CoA (biosynthetic precursors from citric cycle): activates pyruvate carboxylase

ATP + alanine (allosteric effectors-high energy charge): inhibit pyruvate kinase

3. LIVER: both respond to level of blood glucose via F-2, 6-BP

F-2, 6-BP --> F-6-P --> F-2, 6-BP; FBPase2/PFK2

Low glucose = glucagon --> cAMP cascade --> ProteinKinaseA phosphorylates enzyme's Ser --> PFK2 activity inhibited/FBPase2 activity promoted --> less F-2, 6-BP = gluconeogenesis

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Cori cycle

In limited Oxygen, more NADH formed than can be oxidised to NAD+ by respiratory chain

NAD+ formed from pyruvate --> lactate by lactate dehydrogenase

Lactate: muscle --> blood --> liver --> Pyruvate (by LDH) --> Glucose (by gluconeogenesis)

Glucose: liver --> blood --> muscle --> Broken down (by glycolysis)

Opposite pathways occur in different locations, where conditions favour each = cooperative

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Relationship between pathways

Glycolysis = direct energy, substrate for citric acid cycle + oxidative phosphorylation and intermediates for biosynthetic pathways

Gluconeogenesis = maintain blood glucose levels during starvation + vigorous exercise and energy for brain + erythrocytes

Very similar = early organisms produce and break down glucose w/o lots of extra energy

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