KREBS CYCLE

The Meat and Potatoes of Cellular Respiration

Last class... GLYCOLYSIS- We have converted glucose into two 3-

carbon molecules, PYRUVATE that will be further converted

GLYCOLYSIS ENERGY TALLYATP USED

ATP produced

NADH produced

FADH2

produced

2 4 2 0

PYRUVATE OXIDATION

Steps: 1. CO2 is removed from PYRUVATE to form an acetyl group 2. NAD+ removes 2 e + 1p from pyruvate to form NADH + H+

3. CoA combines to the remaining molecule to form ACETYL-CoA*Co-enzyme A is used to shuttle the acetyl group across the membrane

Where are we now?ATP USED ATP produced

2 4

NADH produced FADH2

produced

4 0

Today, we explore KREBS CYCLE

Krebs Cycle

• Named after the biochemist, Hans Krebs• Discovered this series of metabolic rxn’s in 1937

• An 8-step process, each catalyzed by a specific enzyme

• CYCLIC PROCESS, as the product in step 8 is actually the reactant in step 1! – OXALOACETATE (4-carbon)

• THE MAIN SOURCE OF NADH and FADH2

Krebs Cycle: Step 1

• The Acetyl-CoA product from Pyruvate Oxidation combines with OXALOACETATE

• Forming CITRATE– 2 carbons + 4 carbons = 6!

• Notice that Coenzyme A is released at this point. – It was only used to transport

the 2-C acetyl molecule across the mitochondrial membrane

Krebs Cycle: Step 2

• CITRATE (6C) isomerizes to form ISOCITRATE (6C)

• Notice that the –OH group moves from the 3rd carbon to the 2nd carbon

Krebs Cycle: Step 3

• ISOCITRATE (6C) loses a carbon as a CO2 group forming ∞-KETOGLUTARATE (5C)

• NAD + takes 2 more electrons and 1 proton– NAD+ NADH + H+

– Oxidative Phosphorylation

Krebs Cycle: Step 4

• ∞-KETOGLUTARATE (5C) loses a carbon as a CO2 group, but attaches to CoA formingSUCCINYL-CoA (4C)

* ALL Carbons have been used up

• NAD + takes 2 more electrons and 1 proton– NAD+ NADH + H+

– Oxidative Phosphorylation

Krebs Cycle: Step 5

SUCCINYL-CoA(4C) loses its CoA group forming SUCCINATE (4C)

ATP is produced here via a coupled reaction with GTP

GTP GDP + Pi + energy

This energy is used to catalyze ADP + Pi ATP

Krebs Cycle: Step 6

SUCCINATE(4C) is reduced to via FAD to FUMARATE (4C) Notice the C=C bond

• FAD takes 2 electrons and 2 protons– FAD FADH2

– Oxidative Phosphorylation

Krebs Cycle: Step 7

• FUMARATE (4C) has its C=C react with an incoming H2O molecule to form MALATE (4C)

• Remember that we lost a water in Glycolysis! – We use one here.

Krebs Cycle: Step 8

• MALATE(4C) is reduced by NAD+ to reformOXALOACETATE (4C)

• NAD + takes 2 more electrons and 1 proton– NAD+ NADH + H+

– Oxidative Phosphorylation

KREBS CYCLE SUMMARY• Through a series of 8 reactions we have

converted the remaining energy of C-C bonds in our original glucose using NAD+ and FAD carrier molecules

• C6H12O6 + 6O2 6CO2 + 6H2O + 36 ATP– We produced the remaining 4 CO2 molecules – 2 ATP

ATP USED ATP produced NADH produced FADH2

produced

2 6 10 2