Krebs Cycle (aka, tricarboxylic acid (TCA)cycle, citric acid cycle)The wheel is turnin and the sugars a burnin

Overall goal Makes ATP Makes NADH Makes FADH2 Requires some carbohydrate to run

Geography Glycolysis in the cytosol Krebs in mitochondrial matrix Mitochondrion Outer membrane very permeable Space between membranes called intermembrane space (clever huh!)

Inner membrane (cristae) Permeable to pyruvate, Impermeable to fatty acids, NAD, etc

Matrix is inside inner membrane

Conversion of pyruvate to Acetyl CoAO H3C O pyruvate Opyruvate dehydrogenase complex

NAD+

NADH

HSCoA

CO2 H3C

O SCoA

acetyl CoA

2 per glucose (all of Krebs) Oxidative decarboxylation Makes NADH -33.4kJ

Fates of Acetyl CoAO TAG's H3C SCoA Kreb's CO2, ATP, NADH...energy acetyl CoA

no CHO present

ketone bodies

In the presence of CHO an using energy Metabolized to CO2, NADH, FADH2,GTP and, ultimately, ATP

If energy not being used (Lots of ATP present) Made into fat

If energy being used, but no CHO present Starvation Forms ketone bodies (see fat metabolism slides) Danger!

Krebs Cycleacetyl CoA SCoA H3C C OO ONADH C NAD HC OH CH2 malatefumarase

O H2O

O

CoASHHO

H2O

O

O

CO

dehydrogenase

C CH O

O

O

O C C O CH2 C O

+

citrate synthase

O

C CH2 O C C O CH2 citrate CO

O

H

malate

oxaloacetate

aconitase

C C

fumarateO

Kreb's CycleHO

O

succinate

FADH2 FAD O C CH2 CH2 GTPSCoA ONADH

dehydrogenase

O

CoASH GDP

C O O succinate

succinyl CoA synthetase

O

C CH2 CH2 CoASH C CO2Odehydrogenase

NAD

alpha ketoglutarate O O

C NADH C O CO2 CH2 CH2 CO

C CH O HC C O CH2 isocitrate CO O

O

NAD

isocitrate dehydrogenase

alpha ketoglutarate

succinyl CoA

O

Net From Krebs Oxidative process 3 NADH FADH2 GTP

X 2 per glucose 6 NADH 2 FADH2 2 GTP

All ultimately turned into ATP (oxidative phosphorylationlater)

Citrate Synthase Reaction (First)OH3C C O SCoA

+

O

O C C O CH2 C O

O

H2O

CoASHHO

citrate synthaseO

C CH2 O C C O CH2 CO

O

acetyl CoA

oxaloacetate

citrate

Claisen condensation -32.2kJ

Aconitase ReactionO HO

O

C CH2 O C C O CH2 CO

O

O HO

aconitase

C CH HC C CH2 CO O

O

O O

citrate

isocitrate

Forms isocitrate Goes through alkene intermediate (cis-aconitate) elimination then addition

13.3kJ

Isocitrate DehydrogenaseO HO

C CH HC C CH2 CO O

O

OO O

NAD

NADH

CO2

C C O CH2 CH2 CO

O

isocitrate dehydrogenase

O

isocitrate

alpha ketoglutarate

All dehydrogenase reactions make NADH or FADH2 Oxidative decarboxylation -20.9kJ Energy from increased entropy in gas formation

-ketoglutarate dehydrogenaseO

C C O CH2 CH2 CO

O

SCoA

O

CoASH

CO2

NAD

NADH

O

alpha ketoglutaratedehydrogenase

O

C CH2 CH2 CO

alpha ketoglutarate

succinyl CoA

Same as pyruvate dehydrogenase reaction Formation of thioester endergonic driven by loss of CO2 increases entropy exergonic

-33.5kJ

Succinyl CoA synthetaseSCoA O

O GDP GTP CoASH

O

C CH2 CH2 CO

O C CH2

succinyl CoA

succinyl CoA synthetase

CH2 C O O succinate

Hydrolysis of thioester Releases CoASH Exergonic

Coupled to synthesis of GTP Endergonic GTP very similar to ATP and interconverted later

-2.9kJ

Succinate dehydrogenaseO C CH2 C O FAD FADH2Hsuccinyl CoAdehydrogenase

O

O

C C C C

H

CH2 O O

O

O

succinate

fumarate

Dehydrogenation Uses FAD NAD used to oxidize oxygen-containing groups Aldehydes alcohols

FAD used to oxidize C-C bonds 0kJ

FumaraseO O O

O C HC OH CH2 CO O

C CH O

H2OHfumarase

C C

O

fumarate

malate

Addition of water to a double bond -3.8kJ

Malate DehydrogenaseO

O C HC OH CH2 CO ONADNADH

O

dehydrogenase

malate

O

O C C O CH2 C O

malate

oxaloacetate

Oxidation of secondary alcohol to ketone Makes NADH Regenerates oxaloacetate for another round 29.7 kJ

Net From Krebs Oxidative process 3 NADH FADH2 GTP

X 2 per glucose 6 NADH 2 FADH2 2 GTP

All ultimately turned into ATP (oxidative phosphorylationlater)

Total Energy per glucose Cytosol Glycolysis 2 NADH 2 ATP

Mitochondrion Pyruvate dehydrogenase 2 NADH

Krebs 6 NADH 2 FADH2 2 GTP

Total Energy/glucose In mitochondrion: Each NADH makes 2.5 ATP Each FADH2 makes 1.5 ATP GTP makes ATP

So From in mitochondrion 8 NADH X 2.5 ATP/NADH = 20 ATP 2 FADH2 X 1.5 ATP/FADH2= 3 ATP 2 GTP X 1 ATP / GTP = 2 ATP TOTAL in mitochondrion 25 ATP

Total Energy/ glucose Cytosol 2 ATP 2 NADH NADH cant get into mitochondrion In eukaryotes two pathways, transferred to FADH2 get 1.5 ATP/ FADH2 Or transferred to NADH Get 2.5 ATP/ NADH (Not a problem in prokaryotes (why?))

2 NADH X 1.5 ATP Or 2 NADH X 2.5 ATP + Total

= 3 ATP = 5 ATP

=2 ATP 3+ 2 or 5 + 2 so either 5 or 7

ATP/glucose Eukaryotes Mitochondrial: 25 ATP Cytosolic: 5 or 7 ATP Total 30 or 32 ATP/glucose 30 ATP X 7.3kcal X 4.18 kJ = 915 kJATP If 32 ATP kcal = 976 kJ

Prokaryotes 32 ATP X 7.3kcal X 4.18 kJ = 976 kJATP kcal