Download Citric Acid Cycle (CAC) - LSU School of Medicine

Biochemistry is
fun!!!
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Citric Acid Cycle (CAC)
“Kreb Cycle”
Tricarboxylic Acid Cycle
2/3 of O2 consumption needed for
oxidation of Acetyl CoA  CO2
• Occurs exclusively in the
mitochondrion (matrix)
• OAA acts as carrier or acceptor
of acetyl CoA units – is regenerated
• “Burns” acetyl CoA to CO2 – during
this oxidation eˉs from acetyl CoA
are trapped in the form of:
Pyruvate
NADH
Pyruvate Dehydrogenase
Complex “links”
glycolysis to CAC
FADH
+ 2eˉ
+ 2eˉ
+ 2eˉ
+ 2eˉ
GTP  ATP (substrate level
phosphorylation)
The Three Stages of Metabolism (H.A.
Krebs)
The Krebs Cycle
Citric Acid Cycle; The TCA Cycle
• Pyruvate (actually the acetyl group) from glycolysis is
degraded to CO2
– The acetyl group is formed in stage II of metabolism from
carbohydrate and amino acid metabolism
• 1GTP (ATP in bacteria) and 1 FADH2 is produced
during one turn of the cycle
• 3 NADH are produced during one turn of the cycle
• NADH and FADH2 energize electron transport and
oxidative phosphorylation
• Eight reactions make up the Krebs cycle
– If you are given the name of the enzyme, you should be able
to draw the structure of the reactants and products
– You may be given the names of all eight reactions and will
be expected to reproduce the whole cycle
Overview of the Krebs Cycle: A
Mitochondrial Process
Anatomy of the Mitochondrion
• Which membrane is impermeable to
protons and other ions?
• Which membrane will allow for the
transport of molecules up to a molecular
weight of about 1000?
Pyruvate Dehydrogenase Complex
Multimolecular aggregate
3 Enzymes
Cytoplasm Pyruvate
* Pyruvate transporter
5 Coenzymes
5 Reactions
CoA contains the
vitamin Pantothenic acid
Product Inhibition
Coenzymes
Thiamine Pyrophosphate (TTP)
NAD+
FAD+
CoA
Lipoic acid
* Pyruvate mito matrix
Irreversible
Links glycolysis to CAC
Mitochondrial matrix
PDH Deficiency – results in Congenital Lactic Acidosis
Pyruvate cannot enter the CAC and results in ↑ Lactic Acid
Primarily affects the brain – neonatal death
3 Forms – psychomotor retardation
√ Possible treatment is ketogenic diet:
Low in CHO
CAC
High in fats
Produces ketone bodies as an alternate form of energy for the brain
Arsenic Poisoning – Pyruvate Dehydrogenase
Both require lipoic acid as a cofactor
– a-Ketoglutarate Dehydrogenase
Arsenite – Trivalent form of arsenic
I° – Forms a stable complex with the thiol (-SH) group of Lipoic Acid
II° – Glyceraldehyde 3-PO4 step forms complex with inorganic Pi thus prevents ATP
formation in glycolysis
Affects the brain – Death, neurologic problems
Skeletal muscle
Contraction
√ Allosteric Regulation
cAMP dependent
√ Allosteric
Regulation
Carrier
Aldo condensation
The entrance of acetyl CoA does
not ↑ or ↓ intermediates in the CAC
Fluorocitrate
Fluoroacetate
Rat poison
(¯)
Oxidative decarboxylation
ADP (+)
One of the rate limiting Rxs
of the CAC
ATP
NADH¯
e¯
Irreversible (1)
Oxidative decarboxylation
Very similar to the
Pyruvate Dehydrogenase complex
Irreversible (2)
(
¯
)
e¯
From oxidation of
odd number FAs
ADP
ATP. GTP
Succinyl CoA
NADH
GDP
ATP
Nucleoside Biphosphate
Kinase
e¯
“Substrate Level
Phosphorylation”
Irreversible (3)
Oxidation reaction
Hydration reaction
Reversible oxidation reaction
e¯
(4)
Summary
Regulation of the CAC
Dependent on the energy state of
the cell which is reflected by
[ADP] [Pi]
[ATP]
ratio
This ratio determines the rate of
oxidative phosphorylation
Named “Respiratory Control”
of energy production because oxidation
and phosphorylation of ADP must
occur simultaneously
Biochemistry is
fun!!!
La Bioquímica
es divertida!!!