BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015.
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Transcript of BC368: Biochemistry of the Cell II Citric Acid Cycle Chapter 16 March 12, 2015.
BC368: Biochemistry of the Cell IIBC368: Biochemistry of the Cell II
Citric Acid CycleChapter 16
March 12, 2015
3 stages of respiration3 stages of respiration
Production of acetyl-CoA (e.g., during glycolysis and the bridging reaction)
Oxidation of acetyl-CoA via the citric acid cycle
Electon transport and oxidative phosphorylation to produce lots of ATP
Fig 16-1
Glycolysis takes place in the cytosol
The citric acid cycle takes place in the mitochondrial matrix
Mitochondrial ArchitectureMitochondrial Architecture
Fig 16-6
Pyruvate dehydrogenase complexPyruvate dehydrogenase complex
1. Decarboxylation 2. Oxidation3. Acetyl group to CoA 4. Restore enzyme
Fig 16-6
Fig 16-6
Pyruvate dehydrogenase complexPyruvate dehydrogenase complex
Fig 16-6
Step 1. Decarboxylation
Step 1: DecarboxylationStep 1: Decarboxylation
TPP is derived from vitamin B1
Common for decarboxylation reactions
Carries carbon groups transiently
Fig 14-15
Fig 16-6
Pyruvate dehydrogenase complexPyruvate dehydrogenase complex
Fig 16-6
Step 2. Oxidation, with reduction of E2
Step 2: OxidationStep 2: Oxidation
Hydroxyethyl group is oxidized to acetyl group, transferred to lipoamide of E2, which is reduced.
of interest here
Lipoic Acid “Swinging Arm”Lipoic Acid “Swinging Arm”
Swinging arm acyl group carrier
Transfers intermediates between different enzyme sites
Fig 16-6
Pyruvate dehydrogenase complexPyruvate dehydrogenase complex
Fig 16-6
Step 3. Transfer to CoA
Coenzyme ACoenzyme A
Derived from Vitamin B5 (pantothenic acid)
“Activates” the acetyl group
Fig 16-3
Fig 16-6
Pyruvate dehydrogenase complexPyruvate dehydrogenase complex
Fig 16-6
Step 4. Restoring the enzyme
Fig 16-6
Step 4: Restoring the enzymeStep 4: Restoring the enzyme
FAD of E3 reoxidizes dihydrolipoamide.
NAD+ reoxidizes FADH2.
Coenzyme ACoenzyme A
Acetyl group is activated in two ways:
Carbonyl carbon is activated for attack by nucleophiles
Methyl carbon is more acidic
Fig 16-3
A symmetric molecule that acts asymmetric!
Chemically, these carbons are identical!
So both these products should be formed
A symmetric molecule that acts asymmetric!
Chemically, these carbons are identical!
So both these products should be formed
Succinyl-CoA synthetase reactionSuccinyl-CoA synthetase reaction
Hydrolysis of CoA-SH drives phosphorylation of succinate within the enzyme-substrate complex
Succinate transfers its phosphate group to the enzyme
Enzyme phosphorylates GDP
Regulation Regulation
Irreversible reactions are regulated
In general, energy charge is key:
AMP/NAD+ activateATP/NADH inhibit
Product inhibition
Fig 16-19
Anaplerotic ReactionsAnaplerotic Reactions
Example: pyruvate carboxylase, which uses a biotin (vitamin B7) cofactor to carry CO2
Daniel plans to enter the Mr. Colby contest and wants to get jacked. He has begun adding raw eggs to his diet and is up to a dozen a day. Unfortunately, he has been experiencing lactic acidosis during his weight training and hypoglycemia between meals. What’s up with Daniel?
Case Study
Glyoxylate cycle
Fig 16-22
Plants and some microorganisms can convert acetyl-CoA to oxaloacetate for net gain of carbon and net synthesis of TCA intermediates
Intersection with TCA
Fig 16-24
Glyxoylate pathway runs simultaneously with TCA but in a different compartment.
Coordinated regulation
Fig 16-25
Isocitrate is a branch point; its fate depends on relative activities of isocitrate dehydrogenase (TCA) and isocitrate lyase (glyoxylate cycle).
Vania can’t believe that she feels so lousy. Even though it is St. Patrick’s Day weekend and she’s been up all night partying, she’s never felt this bad before. Her head is pounding, and she feels tired, weak, dizzy, and sick to her stomach. She would drink some water, but she lost her Nalgene bottle last week somewhere, and the walk to the dining hall is just way too far.
Case Study
1. What is wrong with Vania?2. What are the consequences of dehydration on metabolism?3. What are the metabolic breakdown products of ethanol?4. What role do these metabolic products play in the citric acid cycle? 5. What would you recommend to Vania?