Ch9 Tricardoxylic Acid Cycle Lecture

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Biochemistry is

fun!!!

La Bioquímica
es divertida!!!
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
FADH Pyruvate Dehydrogenase
Complex “links”
glycolysis to CAC

+ 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 Cytoplasm Pyruvate

Multimolecular aggregate
* Pyruvate transporter
3 Enzymes
5 Coenzymes
5 Reactions * Pyruvate mito matrix

Irreversible
CoA contains the
vitamin Pantothenic acid Links glycolysis to CAC

Product Inhibition Mitochondrial matrix

Coenzymes
Thiamine Pyrophosphate (TTP)
NAD+
FAD+
CoA
Lipoic acid
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


– -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 P i thus prevents ATP
formation in glycolysis
Affects the brain – Death, neurologic problems
Skeletal muscle
Contraction

cAMP dependent
√ Allosteric Regulation

√ Allosteric
Regulation
Carrier
Aldo condensation

The entrance of acetyl CoA does


not ↑ or ↓ intermediates in the CAC

Fluorocitrate OA
A
Fluoroacetate

Rat poison ( ¯)

Oxidative decarboxylation
ADP (+) e¯
One of the rate limiting Rxs Irreversible (1)
of the CAC
ATP
NADH¯
Oxidative decarboxylation
Very similar to the Irreversible (2)
Pyruvate Dehydrogenase complex ( ¯ )
ATP. GTP
e¯ Succinyl CoA
NADH
From oxidation of
odd number FAs
ADP GDP
“Substrate Level
ATP
Nucleoside Biphosphate Phosphorylation”
Kinase

Irreversible (3)
e¯ Oxidation reaction

Hydration reaction
Reversible oxidation reaction


(4)
Summary

Regulation of the CAC


Dependent on the energy state of
the cell which is reflected by
[ADP] [Pi]
ratio
[ATP]

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!!!

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