Overview of Fuel Oxidation IIOverview of Fuel Oxidation II

A/Prof Gareth Denyer

gareth@usyd.edu.au

Beta-oxidation

Fatty acids

blood

cytoplasm

Fatty acyl-CoA

Trapping involves attaching the FA to CoA

Fatty acyl-CoA

CoA

matrix

Swapping the CoA for carnitine allows the FA to get into the mitochondrial matrix

Carnitine often sold as a ‘fat metaboliser’. Claim is that carnitine will help the transport of FA into matrix…. And that this will help burn fat. Sorry, unless you’re specifically deficient in carnitine, it doesn’t actually work..

Hydrogens removed by NAD

NAD

NADH

Fatty acyl-CoA (2 less carbons in FA)

Acetyl-CoA

NAD• Nicotinamide adenine dinucleotide

– Adenine nucleotide attached back-to-back with a nucleotide that has nicotinamide as the “base”

• Nicotinamide is made from nicotinic acid– More commonly called NIACIN or

Vitamin B3

– A supplement in our cereals!– Vital for fuel oxidation

• NAD not only rips hydrogens out of the fuels, it carries them around afterwards.– Actually rips out hydride ions – proton

plus two electrons

PP

Adenine base

ribose

Nicotinamide

ribose

Beta-Oxidation

• As the fatty acids lose hydrogens, they start to break up..

– They do so in a very regular way – by the loss of acetate groups

– These acetate groups are also carried around on CoA – so the acetate does not exist ‘by itself’ but rather as acetyl-CoA

• As a result, the FA becomes shorter by two carbons

• The process of H stripping and FA getting shorter happens sequentially

– Until all the FA is converted into Acetyl CoA

• The scheme is often shown as a ‘sprial’ of degradation.

– With AcCoA and NADH coming off and NAD and CoA coming in.

Fatty acyl-CoA

CoAAcetyl-CoA

Acetyl-CoA

Acetyl-CoA

Acetyl-CoA

Acetyl-CoA

NADH

NADH

NADH

NADH

CoA

CoA

CoA

NAD

NAD

NAD

NAD

FA(n-2)-CoA

FA(n-4)-CoA

FA(n-6)-CoA

FA(n-8)-CoA

Beta-Oxidation• Sequential cutting up of fatty acids

– Into Acetyl CoA– With the release of NADH

• And consumption of CoA and NAD, of course!

• Occurs in the mitochondria

• But what happens to the Acetyl CoA?

Glucose Oxidation

Glucose

blood

cytoplasm

Glucose

Trapping involves phosphorylationWhich uses a little ATP

CO2

Transport into the cells requires GLUTsThere are several forms of GLUT

Hydrogens removed by NAD again… pyruvate breaks up

NAD

NADH

pyruvate

Acetyl-CoA

Glucose 6-phosphate

More investment of ATP… and a bit of rearrangement

Fructose 1,6-bisphosphate

NAD rips out Hs, 6 carbon sugar breaks up into the 3-carbon pyruvate, and ATP is produced

pyruvate

ADP

ATP

matrix

Glucose Oxidation• First part happens in the cytoplasm

– This section returns a very small amount of ATP

– 2 ATPs per glucose

• More energy will be extracted from pyruvate– Pyruvate transported into the mitochondria

and further oxidised

The Krebs CycleFuels

Acetyl-CoA

NADH

NAD

CO2 CO2

• Also called the Tricarboxylic acid (TCA) cycle or the Citric Acid cycle– DON’T PANIC… all you need to

know is the POINT of the cycle• It’s function is to rip out every

last hydrogen and fully oxidise the carbons in acetyl CoA– So heaps of NADH is generated– And the carbon atoms in the

fuels are made into carbon dioxide

• So after all this, the fuels have been converted into carbon dioxide and Hs (which are carried around on NAD)

• BUT WHAT’S THE POINT

Pyruvate and FA-CoA

Energy in Hydrogen!• Hydrogen + Oxygen Water

– Liberates a LOT of energy!– That’s how the Space Shuttle works!

• We’re going to react the hydrogen in NADH with oxygen– But we’re going to do it in a controlled,

stepwise manner in which the energy is harnessed as ATP

e- Transport and H+ pumping

• NADH passes H to a chain of electron transporting complexes in the inner mitochondrial membrane

– The Hs are passed down the chain to oxygen

• As the Hs move down the chain, protons are pumped from the matrix into the cytoplasm

– This creates a PROTON GRADIENT

– Also called a pressure of protons

• The inner mitochondrial membrane is impermeable to protons

– This helps maintain the pressure!

• Note that NAD is regenerated by this

NADH NAD

O2

H2O

H+H+

H+ H+

Making ATP with H+ gradient

• The protons flow (under pressure!) through the F0 channel in the inner mito membrane

– As they come in, they cause another protein (the banana shaped gamma-subunit!) to rotate

– The gamma subunit interacts with the subunits of the F1-ATPase to generate ATP from ADP and phosphate

• The ATP leaves the mitochondria – it does most of its work in the cytoplasm

– When ATP is used to do work, it turns back into ADP and phosphate

– The ADP and phosphate come back into the mitocondria to complete the cycle

H+

ATP ADP

H+

ATP ADP

NADH

NAD

O2

H2O

H+H+

H+ H+

Fuels

Acetyl-CoA

CO2 CO2

ATP ADP

H+