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Transcript
Stages 3 & 4
• These stages are the same for all types
of food = “common metabolic pathway”
• They occur inside the mitochondria
– Citric Acid (Kreb’s) Cycle
– Electron Transport Chain & Oxidative
Phosphorylation
The Citric Acid Cycle
• Maynard G. Krebs
• Hans Adolf Krebs
Citric acid cycle:
Oxidation of the
products of
food breakdown
releases energy
which is
carried by
NADH and
FADH2 molecules
to be turned into
ATP later.
1 ATP, 3 NADH &
1 FADH2 form
with each cycle.
Citric acid
cycle,
Krebs cycle, or
Tricarboxylic
acid cycle:
the main
types of
reactions
found at
each step.
Citric acid cycle
– For every glucose, two acetyl groups enter the
citric acid cycle (Krebs cycle)
• Each two-carbon acetyl group combines with a fourcarbon compound
• Two CO2 molecules are removed (why is this important?)
• Energy captured as 1 ATP, 3 NADH, and 1 FADH2
form from each acetyl group
Dehydration synthesis or condensation reaction
Oxaloacetate 4 C molecule:
Acetyl CoA transfers its acetyl group to
the #2 carbonyl carbon via
the methyl end.
This forms a 6 C citrate molecule.
First dehydration then hydration. Why?
Aconitase enzyme catalyzes both reactions
Citrate:
Note that it is a tertiary alcohol which is not oxidizable.
Isomer is a 2o alcohol (isocitrate) that can be oxidized
First of 4 Redox reactions,
followed by decarboxylation.
NAD+ is the oxidizing agent.
Isocitrate dehydrogenase is the catalyst
Alpha ketoglutarate (a ketone) is formed
when Isocitrate is oxidized,
leading to the reduction of NAD+ to NADH,
& also decarboxylated (first CO2 formed)
Redox reaction #2:
Oxidation of a-ketoglutarate
into 4 C Succinyl CoA (also a ketone)
again more CO2 and NADH are formed
Three enzymes used as a group:
a-ketoglutarate dehydrogenase complex.
H atom must be removed from
sulfhydryl group for coenzyme A to form
a high energy thioester bond.
Thioester bond cleavage (woo!) in Succinyl CoA
& Phosphorylation of Guanosine diphosphate (GDP)
Succinate formation:
The thioester bond in succinyl CoA
is hydrolyzed forming succinate,
with generation of GTP
(which in turn forms ATP)
Steps 6 - 8 involve a series of functional group changes:
oxidation of an alkane (dehydrogenation)
to form an alkene.
Then hydration to form a 2o alcohol,
& finally oxidation (dehydrogenation) to form a ketone.
3rd Redox reaction:
Succinate oxidized by FAD forms fumarate (-2 H atoms).
Fumarate is an alkene with a trans double bond.
The cis form is called maleate and is toxic.
Fumarate undergoes hydration catalyzed by fumarase
which catalyzes addition of water to the double bond.
Only L-Malate isomer is formed
This makes a secondary alcohol.
What reaction do you think will happen next?
Oxidation of L-Malate to regenerate 4 C
Oxaloacetate molecule.
Cycle begins again!
NAD+ is again the oxidizing agent,
So more reduced NADH is formed.
All of these reduced carrier molecules
go on to the last step:
the electron transport chain.
Review: can you…
• Explain what is meant by the term “Metabolism“
• Describe what organelles are and the structure of a
mitochondria.
• Compare and contrast the important intermediate
compounds in metabolic pathways.
• Explain what “High-Energy” means using
phosphate compounds as examples
• List the 4 steps of biochemical energy production
• Give a detailed sequence of the reactions involved
in the Citric Acid Cycle
Electron transport chain
Series of electron carriers
Each carrier exists in oxidized
or reduced form
High energy electrons pass down the
electron transport chain in a series of
redox reactions
These reactions are coupled with ATP
synthesis (oxidative phosphorylation).
They lose energy as they pass along the chain
Oxidative (chemiosmotic)
phosphorylation
Within the Mitochondria of cells:
Chemical and electrical
concentration gradients supply energy to
enzymatically produce ATP from ADP & Pi
6 NADH & 2 FADH2 transport
glucose energy (e- & H+ ions) to E.T.C.
A series of special protein trans-membrane
molecules, cytochrome molecules, a
special lipid (ubiquinone) are all embedded
in the inner membrane of the mitochondria.
The electrons delivered by the carrier
molecules (NADH and FADH2)
begin at high energy levels.
Electron transport chain (ETC)
inner membrane is up to 75% protein by mass
- allows only O2, CO2 and H20 to freely pass
Membrane proteins composed of redox molecules.
Fixed enzyme Complex #1 (entrance of NADH):
Step #1: FMN (Flavin mononucleotide) and
Step #2: FeSP (iron sulphur protein)
Step #3: Mobile enzyme: CoQ (Coenzyme Q) (entrance of FADH2)
Fixed enzyme Complex #2:
Step #4: cyt b (cytochrome b) and
Step #5: cyt c1 (cytochrome C1)
Step #6: Mobile enzyme: cyt c (cytochrome C)
Fixed enzyme Complex #3:
Step #7: cyt a (cytochrome a) and
Step #8: cyt a3 (cytochrome a3)
ETC animation