Metabolism of Glucose

The reaction can run in both directions depending on conditions

At equilibrium, there is no net reaction. i.e. forward and reverse reaction are at the same speed.

Laws of thermodynamics state the energy cannot be created nor destroyed and can only be converted into other forms.

This helps to predict if a reaction is possible and how much energy will required or released

ENERGY AVAILABLE TO DO WORK

DeltaG - Change in free energy as the reaction occurs. Not constant. Dependant on standard free energy change, concentration of reactants and temperature.

DeltaG°' - Standard free energy change when the reaction is conducted in a standard state at pH 7.0 at 25 degrees and 1 atm, when the concentration of reactants is 1.0M. 

Has a characteristic constant value for a given reaction.

If DeltaG is negative - a reaction proceeds spontaneously and with a loss of free energy. The reaction is EXERGONIC

If DeltaG is positive - the reaction is unfavourable or un-spontaneous. The reaction is ENDERGONIC. (The reverse reaction is spontaneous)

If DeltaG = 0 - no free energy change takes place, the system is at equilibrium.

EXERGONIC REACTIONS

• Release energy
• Catabolism of food

ENDERGONIC REACTIONS

• Require energy
• Synthesis of biomolecule
• Muscle contraction
• Nervous excitation
• Active transport

Principal high energy phosphate intermediate in living cells and plays a key role in energy transfer and captureb.

ATP is a nucleoside - same structure in all organisms

1 adenine (nucleotide base) linked to 1 ribose (5-C sugar) linked to chain of 3 phosphate groups

ADP: Adenosine Diphosphate (2 phosphate groups)

AMP: Adenosine Monophosphate (1 phosphate group)

ATP + H2O       ADP + Pi + H+                                          DGo’ = -31 kJ/mol

ADP + Pi + H+          ATP + H2O                                        DGo’ = +31 kJ/mol

• In cells ATP and ADP concentrations vary and are hard to measure hence free energy can only be estimated
• Reactions releasing energy are indirectly coupled to synthesis of ATP from ADP + Pi
• Reactions requiring energy are made favourable my coupling to the breakdown of ATP to ADP + Pi
• Energy released allows reaction to proceed

ATP acts as a donor of high energy phosphate to compounds below it in free energy levels.

CONVERSELY:

ATP formed from ADP by accepting a phosphate group (PO4) from compounds above it in free energy levels

Mechanisms exist for organisms to transfer energy from reactions to form ATP via:

• Substrate Level Phosphorylation
• Oxidative Phosphorylation
• Photophosphorylation (photosynthesis)

Substrate "X" (high energy compound) + ADP ====> Compound "Y" + ATP

Example: 

PEP (phosphoenolpyruvate) + ADP ===> ATP + Pyruvate

The production of ATP from ADP by a direct transfer of a high-energy phosphate group from a phosphorylated intermediate metabolic compound in an exergonic catabolic pathway

Oxidation = loss of electrons

Example: Electron Transport Chain

REDUCED COENZYMES

• Reduced coenzymes are H+ and electron carriers that feet into the Electron Transport System (ETS).
• Transfer of protons and electrons allow for the formation of ATP via oxidative phosphorylation
• Examples include: NAD+/NADH and FAD/FADH2

Total of all the chemical reactions taking place in a cel

Reactions are organised into pathways

Metabolites are formed in pathways are are small molecules that are produced in the degradation or biosynthesis of biopolymers.

CATABOLISM

Process devoted to the degradation of complex substance into smaller simpler molecules.

ANABOLISM

Process concerned with the synthesis of complex organic substance from smaller simpler ones.

Pathways occur as multiple reaction steps

These result in intermediates that cross into other pathways

Specific enzymes will break down an overall reaction into different steps to maximise the production of energy.

Energy is conserved by the production of ATP and reduced co-enzymes.

Common steps can be found in anabolic and catabolic pathways.

Difference lie in key reactions where different enzymes are used to reverse the direction of the pathway.

Control points are often at the beginning of a pathway or at crossover points. Often function via a feeback mechanism.

Three phases of cellular respiration:

• Glycolysis (anaerobic)
• Citric acid (Krebs) cycle (aerobic)
• Electron Transport & Oxidative Phosphorylation (aerobic)

Glycolysis - sequence of reactions converting glycose into pyruvate.

Site of Glycolysis - the Cytosol

Glycolysis in 2 stages:

• Conversion of glucose to fructose 1,6-bisphosphate (followed by cleavage to form glyceraldehyde-3-P) An energy 'investment stage' - ATP utilised.
• Conversion of glyceraldehyde-3-P to pyruvate. An energy 'pay out stage' - ATP produced

Energy requiring reaction - provided by ATP

Glucose becomes phosphorylated

Cannot diffuse out of the cell - 'fixed'

First committed step of pathway

Physiologically irreversible

Reactin catalysed by two different enzymes

Found in all cells

Functions to ensure supply of glucose to tissues even in low glucose concentrations

Ensures large glucose gradient maintained between blood and intracellular environment

Has high affinity (low Km) for glucose

Allosteric enzyme inhibited by G-6-P

Only found in liver and pancrease

Removes glucose from blood following a meal

Has low affinity for glucose (high Km)

GLUCOSE-6-PHOSPHATE (HEXOALDOSE) <==> FRUCTOSE-6-PHOSPHATE (HEXOKETOSE)

Purpose of glycolysis - split glucose into two 3C compounds

Requires aldol split to form an aldehyde and a ketone

Glucose does not have the correct structure for the split but fructose does and therefore G-6-P is converted to Fructose-6-P

FRUCTOSE-6-PHOSPHATE ==(ATP==>ADP)==> FRUCTOSE-1,6-BISPHOSPHATE

Reaction is catalysed by enzyme phosphofructokinase (PFK)

PFK is an allosteric enzyme regulated by ATP levels

High ATP levels - PFK inhibited

Levels of G-6-P increase, hexokinase also becomes inhibited

Mechanism prevents all glucose being used in repsiration

Allows diversion into other pathways

Low ATP levels (high AMP levels) - PFK reactivated

Hexokinase also reactivated - glycolysis restarts

PFK also inhibited by phosphoenolpyruvate and citrate

GLYCERALDEYHYDE-3-P ==(NAD++Pi=>NADH)==> 1,3-BISPHOSPHOGLYCERATE

The reaction is catalysed by glyceraldehyse-3-P dehydrogenase

The reaction generates NADH that will feel into electron transport.

1,3,-BISPHOSPHOGLYCERATE ==(ADP==>ATP)==> 3-PHOSPHOGLYCERATE

The reaction is catalysed by phosphoglycerate kinase

Removal of the phosphate groups results in a release of energy, captured by formation of ATP - an example of substrate level phosphorylation

3-PHOSPHOGLYCERATE <====> 2-PHOSPHOGLYCERATE

Reaction is catalysed by phosphoglycerate mutase

Intramolecular transfer of the phosphoryl group prepares the moelcule for the final stages of glycolysis.

2-PHOSPHOGLYCERATE <=====> PHOSPHOENOLPYRUVATE (PEP) + H2O

Reaction catalysed by enolase

The penultimate step redistributes energy to produce a high energy phosphate, phosphoenolpyruvate (PEP)

PEP ====(ADP==>ATP)===> PYRUVATE

Reaction catalysed by pyruvate kinase

Transfer of the phosphate group from PEP to generate pyruvate releases energy as ATP (substrate level phosphorylation)

STAGE ONE

• 2 molecules ATP are used to form F-1,6-bisP

STAGE TWO

• 4 moleules ATP generated (2 for each G-3-P)

NET GAIN OF ATP = 2 MOLECULES

2 NADH GENERATED

If oxygen is absent: anaerobic conditions, fermentation or lactate formation

If oxygen is present - aerobic conditions, further oxidation and more energy captured in the citric acid cycle and electron transport chain.