1. Why is it so complicated?

2. Keeping track of Carbons

3. How is it regulated?

From Lehninger
Principles of Biochemistry
1. Why is it so
complicated?
 Citric acid cycle components are important biosynthetic intermediates

Amphibolic pathway,
i.e., serves in both catabolic & From Lehninger

anabolic processes Principles of Biochemistry

Anaplerotic reactions replenish citric acid cycle intermediates

Anaplerotic (meaning "filling up" in Greek)

pathways replace lost carbon compounds that
TCA Cycle are drawn out of central metabolism to produce
other cell constituents.

From Lehninger
Principles of Biochemistry
2. Keeping track of Carbons
 Each turn of the citric acid cycle produces
3 NADH, 1 FADH2, 1 GTP (or ATP), and 2 CO2

TCA Cycle

From Lehninger
Principles of Biochemistry
 Keeping track of
the carbon atoms

From oxaloacetate,
From Lehninger
not acetyl-CoA
Principles of Biochemistry
 From Lehninger
Principles of Biochemistry
 Under physiological conditions
Standard free energy G' = -32.2 kJ/mol except for 1,3 & 4 all reaction have
G values closer to zero
changes for TCA cycle

G' = 29.7 kJ/mol

G' = 13.3 kJ/mol

G' = -3.8 kJ/mol

G' = -20.9 kJ/mol

G' = 0 kJ/mol

G' = -2.9 kJ/mol G' = -33.5 kJ/mol

From Lehninger
Principles of Biochemistry
How is it regulated?
Under physiological
conditions except for 1,3 & 4
G' = -32.2 kJ/mol all reaction have G values
closer to zero

Standard free energy

changes for TCA cycle G' = -20.9 kJ/mol

G' = -33.5 kJ/mol

From Lehninger
Principles of Biochemistry
Regulation of
Citric Acid
Cycle

The citric acid

cycle is regulated
at its three
exergonic steps From Lehninger
Principles of Biochemistry
 The Glyoxylate Cycle
Electron micrograph of germinating cucumber seed

In germinating seeds triacylglycerol is converted to acetyl-CoA

& then to glucose using glyoxylate pathway
The Glyoxylate Cycle
A variant of TCA for plants and bacteria
• Acetate-based growth
• Net synthesis of carbohydrates and other
intermediates from acetate is not possible with
TCA
• Glyoxylate cycle offers a solution for plants and
some bacteria and algae
• The CO2-evolving steps are bypassed and an
extra acetate is utilized
• Isocitrate lyase and malate synthase are the
short-circuiting enzymes
 Glyoxalate Cycle

(in plants,
some invertebrates, and
in some microoranisms,
e.g., E. coli)

From Lehninger
Principles of Biochemistry
From Lehninger
Principles of Biochemistry
 From Lehninger
Principles of Biochemistry
Chapter 19
Electron Transport & Oxidative Phosphorylation
From Lehninger
Principles of Biochemistry
Ubiquinone (coenzyme Q) (from lipids lecture)
6 carbon

C6H12O6 + 6 O2  6 CO2 + 6 H2O

2 x 3 carbon

2 CO2

2 x 2 carbon

The carbon is
already converted to
2 x 2 CO2
CO2.
What is left is
electrons in the form
of NADH and
FADH2.
From Garrett & Grisham
 {80% proteins}

{30-40% lipids & 60-70% proteins}

Provide inner
membrane Intermembrane
space
with large
surface area

Porins are transmembrane
channels for small molecules
Outer Membrane
• Contains porin
• Allows free diffusion of molecules
with molecular weight less than
10,000
Inner Membrane
• Impermeable to molecules & ions
 Matrix
• contains all of TCA cycle
enzymes {except, succinate
dehydrogenase which is located in
the inner membrane}
• contains circular DNA,
ribosomes and enzymes
required to synthesize proteins
encoded within the
mitochondrial genome

From Lehninger
Principles of Biochemistry
Separation of functional complexes
of the respiratory chain

Components of the electron

transport chain can be purified
from the mitochondrial inner
membrane

From Lehninger
Principles of Biochemistry