The Citric Acid Cycle

Regulation of Glycolysis

Enzymes in glycolysis and gluconeogenesis are allosterically regulated (Feedback regulation)

• For glycolysis, we will mostly regulate at ____, ___, and ___

Gly-1, Gly-3, and Gly-10

Cellular Respiration

The flow of electrons, through or within a membrane, from reduced coenzymes to an external electron acceptor (Generates ATP)

Common electron acceptor

O2 (Aerobic Respiration)

Aerobic Respiration Part 1

Completely oxidizes pyruvate and Yields more energy than glycolysis alone

Aerobic Respiration (Part 2)

Involves the transfer of electrons from NADH/FADH2 to oxygen and Takes place in the mitochondria

Stages of Aerobic Respiration
• Stage 1:

Glycolysis

Stages of aerobic respiration: Stage 2

Oxidation of Pyruvate to Acetyl CoA

Stages of aerobic respiration: Stage 3

Citric Acid Cycle (Krebs Cycle)

Stages of aerobic respiration: Stage 4

Electron Transport

Stages of aerobic respiration: Stage 5

Oxidative Phosphorylation

Anaerobic fermentation uses an internal electron acceptor rather than an external one like oxygen.
• Which one can yield more energy?
• Why?

Anaerobic fermentation uses an internal electron acceptor rather than an external one like oxygen

Mitochondria

Found in virtually all aerobic cells of eukaryotes

Mitochondria (part 2)

More are present where there is greater energy needed (muscle cells)

True or False:

Mitochondria are present in both chemotrophic and phototrophic cells

True

Outer Membrane and Intermembrane Space

Not a significant permeability barrier for ions

Therefore intermembrane space is

continuous with cytosol

Inner membrane folds into

cristae

Ions accumulate in

intracristal spaces

Inside portion:

matrix

Matrix

Contains many enzymes, ribosomes, and DNA

Membrane contains

electron transport chain

What Happens in the Mitochondria? (part 1)

Conversion of pyruvate to acetyl CoA (Matrix)

What Happens in the Mitochondria? (part 2)

Electron Transport Chain and Oxidative Phosphorylation (Inner Membrane (Cristae))

The Fate of Pyruvate

Fermentation. Converted to Acetyl CoA → to Aerobic Respiration

Pyruvate is Converted to ____ ____

Acetyl CoA

Pyruvate is Converted to Acetyl CoA using ?

Oxidative decarboxylation

What is Coenzyme A?

Contains B vitamin pantothenic acid. Thiol can form thioester bonds

The Citric Acid Cycle overview (part 1)

Takes in 2 carbons from pyruvate and Releases 2 carbons as CO2

The Citric Acid cycle overview (part 2)

Reduces coenzymes NAD+ and FAD and Makes 2 ATP per glucose (1 per pyruvate)

The Citric Acid Cycle

Step 1

Begins with oxidative decarboxylation of pyruvate to acetyl CoA. Releases 1 CO2 and Reduces 1 NADH

The Citric Acid Cycle

Step 2

2 carbons from acetyl CoA added to 4-carbon oxaloacetate. Forms citrate and CoA-SH released (water required)

The Citric Acid Cycle 

step 3

Citrate converted to isocitrate

The Citric Acid Cycle 

step 4 (part 1)

First: isocitrate converted to alpha-ketoglutarate. Then Oxidation of isocitrate

The Citric Acid Cycle 

step 4 (part 2)

Decarboxylation, CO2 released, and NAD+ reduced to NADH

The Citric Acid Cycle 

step 5 (part 1)

alpha-ketoglutarate is oxidized to succinyl CoA, and Another decarboxylation

The Citric Acid Cycle 

step 5 (part 2)

CoA replaces carboxyl, CO2 released, and NAD+ oxidized to NADH

The Citric Acid Cycle 

step 6 (part 1)

Succinyl CoA converted to succinate and Energy in thioester bond used to generate ATP

The Citric Acid Cycle 

step 6 (part 2)

GTP produced, energy transferred to ATP

The Citric Acid Cycle 

step 7

Succinate oxidized to fumarate, FAD reduced to FADH2 and C=C double bond formed

The Citric Acid Cycle 

step 8

Fumarate hydrolyzed to malate, C=C double bond replaced with C-C, and 1 H and 1 OH added

The Citric Acid Cycle 

final step 

Malate is oxidized to oxaloacetate, NAD+ reduced to NADH, and Oxaloacetate reformed (can do cycle again)

The Citric Acid Cycle: Summary
• Input:

1 Acetyl CoA

The Citric Acid Cycle: Summary

output

2 CO2 (plus 1 from pyruvate decarboxylation), 1 GTP → 1 ATP, 1 FADH2 and 3 NADH (plus 1 from pyruvate decarboxylation)

Summary So Far: Glycolysis to Citric Acid Cycle

Per glucose:
 Glycolysis:

2 ATP and 2 NADH

Summary So Far: Glycolysis to Citric Acid Cycle

Per glucose:

Citric Acid Cycle

6 CO2, 2 ATP, 2 FADH2, and 8 NADH

The Citric Acid Cycle: Regulation (Part 1)

Citric acid cycle enzymes are subject to allosteric regulation

The Citric Acid Cycle: Regulation (Part 2)

Acetyl CoA and NADH inhibit pyruvate dehydrogenase / NADH inhibits malate dehydrogenase

The Citric Acid Cycle: Regulation (Part 3)

NADH inhibits isocitrate dehydrogenase / NADH and succinyl CoA inhibit alpha-ketoglutarate dehydrogenase

Fat as a Source of Energy (part 1)

The cell stores energy long-term as fat (triacylglycerols) / Glycerol and 3 fatty acid chains

Fat as a Source of Energy (part 2)

First: fatty acid chains separated from glycerol / Fatty acids attached to CoA to make fatty acyl CoA

Fat as a Source of Energy (part 3)

β-Oxidation degrades fatty acid / Releases FADH2, NADH, and Acetyl CoA