Krebs cycle

phosphofructokinase *

hexose kinase

aldolase

triose phosphate isomerase

phosphogyceraldehyde dehydrogenase

phosphoglycerate kinase

pyruvate kinase *

Lactate (or ethanol + CO2)

NAD+ NADPH

To TCA cycle

The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other pathways, e.g., fatty acid oxidation & amino acid metabolism.

The outer membrane contains large VDAC channels, similar to bacterial porin channels, making the outer membrane leaky to ions & small molecules.

matrix

inner membrane

outer membrane

inter- membrane

space

mitochondrion

cristae

Glycolysis occurs in the cytosol of cells.

Pyruvate enters the mitochondrion to be metabolized further.

Mitochondrial Compartments:

It contains various transport catalysts, including a carrier protein that allows pyruvate to enter the matrix.

It is highly convoluted, with infoldings called cristae.

Embedded in the inner membrane are constituents of the respiratory chain and ATP Synthase.

matrix

inner membrane

outer membrane

inter- membrane

space

mitochondrion

cristae The inner membrane is the major permeability barrier of the mitochondrion.

Pyruvate (3 C)

Acetyl Co A (2C)NAD+ NADH +CO2

Oxaloacetate (4C) Citrate (6C)

Ketoglutarate (5C)

NAD+ NADH +CO2

Succinyl CoA (4C)

CoA + NAD+ NADH +CO2

GDP GTP +CoA

Succinate

Fumarate

Malate

FADH2FAD

HOH

NAD+ NADH

Pyruvate Dehydrogenase, catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA.

H3C C C O−

O O

C S

O

H3C CoA

HSCoA

NAD+NADH

+CO2

P yruv ateD ehydrogenase

pyruvateacetyl-CoA

Acetyl CoA functions as: input to Krebs Cycle, where the acetate moiety is

further degraded to CO2. donor of acetate for synthesis of fatty acids, ketone

bodies, & cholesterol.

glucose-6-P

Glycolysis

pyruvate fatty acids

acetyl CoA ketone bodies cholesterol

oxaloacetate citrate

Krebs Cycle

3 ATP

3 ATP

3 ATP

2 ATP

3 ATP1 ATP

Pyruvate (3 C)

Acetyl Co A (2C)NAD+ NADH +CO2

Oxaloacetate (4C) Citrate (6C)

Ketoglutarate (5C)

NAD+ NADH +CO2

Succinyl CoA (4C)

CoA + NAD+ NADH +CO2

GDP GTP +CoA

Succinate

Fumarate

Malate

FADH2FAD

HOH

NAD+ NADH

Scorecard:

2 ATP/glucose anaeobic gycolysis

In addition, aerobically we get

~6 ATP from glycolysis NADH

~6 ATP from pyruvate dehydrogenase NADH

~18 ATP from TCA cycle NADH

~4 ATP from TCA cycle FADH

2 ATP from TCA cycle GTP

So: aerobic metabolism ‘classically’ adds ~36 ATP, giving 38 altogether. As I’ll make clear, a bit less than this is made in reality.

Respiration

• Glycolysis and the TCA cycle produce NADH, FADH2 and ATP (via GTP) as primary products, CO2 as a byproduct

• Most of the ATP is made by transfering electrons from NADH and FADH2 to oxygen, forming water

• This is done in the inner membranes of mitochondia and is called respiration

Succinate UQ reductase

2H+

B

AH2

A

C2e-

2e-

2e-

2H+-

Inside (N Side)

Outside (P Side)

Mitchell’s Chemiosmotic Loop