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Title: The Krebs Cycle
Description: The note explain about the process of krebs cycle
Description: The note explain about the process of krebs cycle
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The Krebs Cycle
• Living organism obtain
energy from respira9on
ü There are 2 types of respira9on
a) External respira9on
-‐ involves exchange of O2 and CO2 at respiratory surface
...
-‐ involve the break down of complex organic molecules,
such as glucose into simpler molecules with the release
of energy in the form of ATP molecules
...
-‐ anaerobic respira9on occurs if O2 absent
...
ü 1 glucose molecule produces 2 pyruvate molecules, so, 2
acetyl CoA molecules are formed
...
•
Step 1: Condensa
...
Thermodynamically, the equilibrium
is in favour of the products
...
Citrate is a
tricarboxylic acid, and the Krebs cycle is also known as the tricarboxylic
acid (or TCA) cycle
Step 2
...
on of Citrate
• As we will see later on in the Krebs cycle, there will be a
decarboxyla+on reac9on
...
However, the exergonic character of the next
reac9on in the cycle helps shiY the equilibrium of this reac9on towards the
right
...
Each can
adopt either the L-‐ or D-‐ rotamer, thus there are 4 possible isomers of this
molecule
• Aconitase only produces the single form of Isocitrate (D-‐Isocitrate)
...
on of CO2 by an NAD+
linked enzyme
• The Krebs cycle contains two oxida9ve decarboxyla9on steps; this
is the first one
• The reac9on is catalyzed by the enzyme Isocitrate dehydrogenase
• The reac9on involves dehydrogena9on to Oxalosuccinate, an
unstable intermediate which spontaneously decarboxylates to give
α-‐Ketoglutarate
• The reac9on is exergonic
...
Thus, this step is referred
to as an oxida/ve decarboxyla/on step
Step 4: A Second Oxida
...
on Step
• This step is performed by a mul9-‐enzyme complex, the α-‐Ketoglutarate
Dehydrogena+on Complex
• The mul9-‐step reac9on performed by the α-‐Ketoglutarate Dehydra+on
Complex is analogous to the Pyruvate Dehydrogenase Complex, i
...
an α-‐
keto acid undergoes oxida9ve decarboxyla9on with forma9on of an acyl-‐
CoA
• Overall, this oxida9ve decarboxyla9on step is more exergonic than the
first oxida9ve decarboxyla9on step
Summary of Krebs cycle reac
...
on
• Succinyl-‐CoA is a high poten9al energy molecule
...
In animals, GDP is
the substrate in the reac9on with forma9on of GTP (which is then used to
form ATP by Nucleoside Diphosphokinase)
Step 6: Flavin-‐Dependent
Dehydrogena
...
• Both Succinate and Oxaloacetate are 4-‐carbon compounds
• The first step in the conversion is the dehydrogena9on of Succinate to
yield Fumarate
• In this reac9on a C-‐C bond is being oxidized to produce a C=C bond
...
• The redox coenzyme for this reac9on is therefore FAD, rather than NAD+
(FAD is a more powerful oxidizing agent compared to NAD+)
• FAD is covalently bound to the Succinate Dehydrogenase molecule (via a
his9dine residue)
• The FADH2 has to be oxidized for the enzyme ac9vity to be restored
...
• Succinate Dehydrogenase is +ghtly bound to the mitochondrial inner
membrane
• Succinate Dehydrogenase is stereo-‐specific: the trans-‐ isomer (Fumarate) is
produced and not the cis-‐ isomer (Maleate)
Step 7: Hydra
...
Furthermore, the enzyme can not use D-‐
Malate as a substrate in the reverse reac+on
Step 8: A Dehydrogena
...
on that will
Regenerate Oxaloacetate
•
L-‐Malate (Malate) is dehydrogenated to produce Oxaloacetate by the enzyme Malate Dehydrogenase
•
This is a highly endergonic reac9on and so the equilibrium strongly favours the reactants over the
products
...
e
...
• Since every molecule of glucose produces 2 units of
acetyls, so 1 molecule of glucose will produce 2 ATP
molecules, 4 CO2 molecules, 6 NADH molecules, and 2
FADH2 molecules
...
• This cycle produces valuable intermediate compounds
that can be used to synthesize substances such as amino
acids, glycerol, chlorophyll and facy acids
Title: The Krebs Cycle
Description: The note explain about the process of krebs cycle
Description: The note explain about the process of krebs cycle