Glycolysis This stage of respiration is the “setting up” stage Glucose is prepared for further breakdown to produce more ATP Reduced NAD created here has the potential to make ATP in later stages

Link reaction Pyruvate produced in glycolysis contains lots of potential energy that can be channelled into ATP synthesis. This will not happen without the presence of oxygen. Only when oxygen is present is pyruvate actively transported to the mitochondria. Here pyruvate undergoes a link reaction to become acetyl coenzyme A

Link reaction Pyruvate loses a hydrogen (becomes dehydrogenated) Pyruvate also loses carbon as carbon dioxide (becomes decarboxylated) This results in the formation of a substance called acetyl coenzyme A Acetyl co-A is fixed in the matrix of the mitochondria. From here it can enter the next stage of aerobic respiration, the Kreb’s cycle. The hydrogen acceptor molecule is NAD.

The Link Reaction 3C Pyruvate 2C Acetate 2C Acetyl CoA NAD Reduced NAD coenzyme A (CoA)

Summary of Link Reaction The link reaction occurs twice for every glucose molecule! Two pyruvate molecules are made for every glucose that enters glycolysis. This means the link reaction and the next stage (Krebs cycle) also happen twice. 2 acetyl CoA molecules go into the Krebs cycle 2 CO2 molecules are released as a waste product of respiration 2 molecules of reduced NAD are formed and go to the last stage (oxidative phosphorylation)

The Krebs Cycle

Learning Outcomes (g) outline the Krebs cycle, with reference to the formation of citrate from acetate and oxaloacetate and the reconversion of citrate to oxaloacetate (names of intermediate compounds are not required); (h) explain that during the Krebs cycle, decarboxylation and dehydrogenation occur, NAD and FAD are reduced and substrate level phosphorylation occurs.

The Krebs Cycle A series of chemical reactions that occur in the matrix of the mitochondrion Pyruvate has a carboxyl group removed(pyruvate decarboxylase), which eventually becomes carbon dioxide. Coenzyme A accepts an acetyl group to become acetyl coenzyme A Acetyl is completely broken down into carbon dioxide Hydrogen is removed to form reduced coenzymes (pyruvate dehydrogenase) More ATP is synthesised directly - substrate level phosphorylation

The Krebs Cycle 2C acetyl combines with a 4C compound called oxcaloacetate. (coenzyme A offloads the acetyl so is free to collect more This forms a 6C compound called citrate

The Krebs Cycle 6-carbon citrate is an intermediate compound that is rapidly decarboxylated in a series of enzyme-linked reactions This compound is also dehydrogenated The carrier molecules NAD and FAD combine with the liberated hydrogen Carbon is released as carbon dioxide It is eventually broken down to 4C oxaloacetate again.

Dehydrogenation Decarboxylation

Importance of Krebs Cycle The Krebs cycle breaks down acetyl to CO2 Decarboxylase and dehydrogenase enzymes also release hydrogen atoms. Coenzyme hydrogen carriers become reduced (NADH/FADH). This is really important for later stages of ATP synthesis. Acetyl can be produced from fatty acids and amino acids. The body will metabolise any substrate available to produce ATP.

The Outcome of the Krebs Cycle Three molecules of reduced NAD One molecule of reduced FAD One molecule of ATP produced by substrate-level phosphorylation Two molecules of CO2 One molecule of regenerated oxaloacetate PER ONE PYRUVATE MOLECULE

The outcome of the Krebs cycle for 2 molecules of pyruvate Product per molecule of glucose Link reaction Krebs cycle Reduced NAD 2 6 Reduced FAD Carbon dioxide 4 ATP

Control of the Krebs cycle Allosteric feedback mechanisms: High levels of ATP inhibit first three stages of Krebs cycle Following enzymes then become inhibited by high levels of reduced coenzyme (NADH/FADH) to stop the cycle from continuing This means substrates are only broken down as and when needed High concentration of citrate inhibits continual glycolysis of glucose, therefore regulating the amount of substrate going through the pathways

What is allosteric inhibition? Enzymes involved in respiration pathways can be inhibited by an inhibitor binding temporarily to somewhere other than the active site, changing the active site.