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Lecture 12

MBB 231 Lecture Notes - Lecture 12: Coenzyme Q10, Transmembrane Protein, Atp Synthase


Department
Molec Biol & Biochem
Course Code
MBB 231
Professor
Stephanie Vlachos
Lecture
12

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Lecture 12 Metabolism Aerobic Respiration
Structure and function of mitochondria
Mitochondria are located within a cell where the most intense metabolic activity occurs
Specific functions are localized to various compartments
1. Outer membrane
Contains porins
Which allow the free movement of small molecules and ions across the
outer membrane
2. Inner membrane (very selective)
Permeability barrier to most solutes
Highly folded into cristae that project into the interior of the mitochondria
Respiratory proteins are embedded in the inner membrane (75% protein)
The density of cristae is related to the respiratory activity of the cell
3. Matrix
Within the inner membrane; contains most of the enzymes associated with
mitochondrial function, in addition to DNA and ribosomes
4. Intermembrane Space
Between the outer and inner membranes
Oxidation of glucose and other sugars begins in the cytoplasm, producing pyruvate
Pyruvate passes through the porins in the outer membrane and into the intermembrane space
Pyruvate symporter in the inner mitochondrial matrix transports pyruvate into the matrix along
with a proton
Aerobic respiration occurs in the presence of oxygen leads to conversion of pyruvate to acetyl CoA
by oxidative decarboxylation
The formation of acetyl CoA from pyruvate is a key irreversible step in animals
Animals are unable to convert acetyl CoA into glucose
The oxidative decarboxylation of pyruvate into acetyl CoA commits the carbon atoms of glucose in
two principle fates
1. Oxidation to CO2 by citric acid cycle
2. Incorporation into lipid
Metabolic fates of Acetyl CoA
1. Oxidation to CO2 in the citric acid cycle
2. Biosynthesis of fatty acids
3. Biosynthesis of cholesterol
4. Ketogenesis
Overview of the citric acid cycle
Molecular oxygen is not involved
Pyruvate is fully oxidized to CO2 energy released is used to drive ATP synthesis
In stage II pyruvate is transported to mitochondrial matrix and is metabolized to CO2 and Acetyl CoA
plus one molecule of NADH by the pyruvate dehydrogenase complex (oxidative carboxylation)
Acetyl CoA arises in two ways still transfers its acetate group to oxaloacetate to generate citrate
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Acetyl CoA contains a high energy thioester bond
The citric acid cycle
1. Two carbons enter the cycle from acetyl CoA, and are joined to the four-carbon acceptor molecule
oxaloacetate to form citrate
2. Decarboxylation occurs at two steps in the cycle so that the input of two carbons is balanced by the
loss of two carbons as CO2
3. Oxidation occurs at four steps with NAD+ as the electron acceptor in three cases and FAD in one
case
4. ATP is generated at one point, with GTP as an intermediate in animal cells
5. One turn of the cycle is complete upon regeneration of oxaloacetate
NET YIELD OF ONE GLUCOSE MOLECULE:
Glucose + 10NAD+ + 2FAD + 4ADP + 4Pi 6CO2 + 10NADH + 2FADH2 + 4ATP
Regulation of citric acid cycle
Most of the control involves allosteric regulation of four key enzymes
o Pyruvate dehydrogenase
o Isocitrate dehydrogenase
o Alpha-ketoglutarate dehydrogenase
o Malate dehydrogenase
The citric acid cycle plays a role in the catabolism of fats and proteins
Fats are highly reduced compounds that free up more energy upon oxidation than carbohydrates
Stored as triacylglycerol
Catabolized into glycerol and free fatty acids
Lots more ATP produced
Protein Proteolysis
Of the 20 amino acids, three of them give rise to pyruvate or CAC intermediates directly
o Alanine: pyruvate
o Aspartate: oxaloacetate
o Glutamate: alpha-ketoglutarate
Stage IV: Electron Transport
Key to the great ATP yields characteristic of aerobic respiration is represented by the reduced
coenzyme molecules NADH and FADH2
90% of the potential free energy present in one glucose molecule is conserved in the 12
molecules of NADH and FADH2 that are formed when a molecule of glucose is oxidized to CO2.
Electron transport is accompanies by ATP synthesis (stage V), these processes are functionally
linked by the electrochemical proton gradient
Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of
electrons from NADH or FADH2 by a series of electron carriers
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