Bioenergetics and Oxidative Metabolism I

Overview

Oxidation and reduction always occur together.

All reactions in nature are spontaneous reactions.

ATP Cycle

Catabolic reactions generate ATP, anabolic reactions use ATP.

ATP contains two phosphoanhydride bonds that can be broken to
generate energy.

Gibbs Free Energy

A negative delta G indicates that the reaction is spontaneous.

All reactions in nature are driven toward a lower enthalpy, a
higher entropy or a lower Gibbs free energy.

Three Intermediates for Oxidative Metabolism

Proteins can all be broken down to make pyruvate or Acetyl-CoA.

Glucose can be used to make pyruvate.
Fatty acids can be used to make Acetyl-CoA.
RBC do not have mitochondria and uses anaerobic metabolism of
glucose.

Pyruvate

Pyruvate is an alpha keto carboxylic acid as is all naturally

occurring AA.
Pyruvate is glucogenic and Acetyl-CoA is ketogenic.
Pyruvate is oxidative decarboxylated to form acetyl-CoA and
CO2, this reaction has large negative delta G and is irreversible.
CoA contains a sulfhydryl group that is used to bind Acetyl group
or fatty acids.
CoA functions as a carrier in many different pathways.
PDH is found in the mitochondrial matrix that converts pyruvate
to Acetyl-CoA and CO2 while producing NADH in the process.

Pyruvate Dehydrogenase

PDH consists for 3 catalytic subunits, two regulatory subunits,

one binding protein and five cofactors.
Thiamine pyrophosphate (TPP) bound to E1 non-covalently,
thiamine deficiency causes beriberi.

Lipoic acid bound to E2 covalently, exist in oxidized form and

reduced form, passes electrons to FAD in E3. Inhibited by arsenic
trioxide.
Pyruvate dehydrogenase kinase (PDK 3)regulates PDH by
phosphorylating the E1 and inhibits it.
When there is no substrate, lipoic acid is in oxidized form it
stimulates PDK3 PDK3 phosphorylates E1 of PDH and inhibits
it.
NAD and and NADP are electron carriers that carry 2 electrons
and one H in the nicotinamide ring.
Nicotinamide ring is made from niacin (Vit B3)
FAD and FMN are electron carriers and carry 2 electrons and 2 H
on the flavin ring.
FAD and FMN are made from riboflavin (vit B2).
All flavoenzymes are yellow.

Regulation of Pyruvate Dehydrogenase

PD products NADH and Acetyl-CoA inhibit E1 activity directly or

stimulate PD kinase.
PD kinase phosphorylate E1 to inactivate it.
PD substrates pyruvate, CoA, NAD inhibit PD kinase.
PD phosphatase activates PD by removing phosphorylation.

The Krebs Cycle

Major function is to produce electron carriers to power electron

transport chain.
Each Acetyl-CoA generates 3 NADH, 1 FADH2 and 1 GTP.
The 2 Carbons in Acetyl-CoA is oxidized to CO2.
Approx 9 ATP are generated.

Energy Produced By Krebs Cycle

2.5 ATP per NADH

1.5 ATP per FADH2
1 ATP per GTP

Regulation of Krebs Cycle

Substrates
Oxygen
Need for energy
Allosteric regulation of enzymes

Anaplerotic reaction increase amounts of Kreb cycle intermediates.

Pyruvate Carboxylase: Pyruvate +CO2+ATP Oxaloacetate

+ADP+Pi
Glutamate dehydrogenase: Glutamate+NAD alpha KG
+NADH+H+NH4