10.1-10.2 Step Zero of the Citric Acid Cycle Flashcards
What are two other names for the citric acid cycle?
Kreb’s or TCA cycle
Where does it take place?
Mitochondria
How much ATP is NADH worth?
2.5 ATP
How much ATP is FADH2 worth?
1.5 ATP
How much ATP is GTP worth?
1 ATP
When EC is low?
Pyruvate is metabolized by pyruvate dehydrogenase which forms acetyl-CoA and CO2
How is pyruvate transported in the mitochondria?
Transmembrane transporter protein
What does pyruvate dehydrogenase do?
Converts pyruvate to Acetyl CoA
What 5 coenzymes are needed?
NAD+/NADH
FAD/FADH2
CoA/CoAsh
TPP
a-lipoleic acid
NAD full name
nicotinamide adenine dinucleotide
FAD full name
Flavin adenine dinucleotide
CoA name
Coenzyme A
TPP name
Thiamine pyrophosphate
a-lipoleic acid name
Lipoamide
NAD characteristics
Derived from niacin (B3), involved in 200+ reactions, Transfers 2 electrons at once as hydride ion
Pellagra
niacin deficiency, rash/diarrhea/neurologic, fish veggies and poultry
FAD characteristics
derived from riboflavin (B2), flavoproteins, a precursor to FAD and FMN.
Reduced to FADH2 by transfer of two electrons; one electron transported at a time; semiquinone intermediate
Cheilosis
Riboflavin deficiency, swelled or cracked lips, almonds/meat/dairy, destroyed by light
CoA characteristics
derived from pantothenic acid (B5), required for energy conversion in citrate cycle, cofactor in production of fatty aces, acetylcholine, heme, cholesterol.
Function - carry acetate in form of CoA
Pantothenic acid deficiency
rare, found in most foods (chicken, yogurt, avocados)
How do you get CoA across the membrane?
Nucleotide can’t cross; CoA degraded by enzymes into pantothenic acid, travels through circulation, crosses cell membrane, converted back to CoA with ATP and cysteine additon
TPP characteristics
derived from thiamin (B1), absorbed in gut and phosphorylated, pulls acetyl group off pyruvate
Beriberi
thiamin deficiency; anorexia/cardio problems/neurologic; brown rice and fortified grains - milling white rice removes bran and thiamin; raw fish and silkworms contain thiaminase which degrades thiamine
ɑ-lipoic acid characteristics
Synthesized in plants & animals
– Also in broccoli, liver, spinach & tomato
* Provides reactive disulphide for redox rxns
* Receives acetyl from TPP and transfers it to CoA
The ball in the mechanism
Citrate Cycle Reaction 0
Substrates: pyruvate, NAD+, CoA
Product: acetyl-CoA, NADH, COs, H+
Enzyme: Pyruvate dehydrogenase complex (E1, E2, E3)
Irreversible
Reaction Zero for citric acid cycle
Pyruvate +CoA + NAD+ –> Acetyl CoA + CO2 +NADH +H+
Steps 1-3 of pyruvate dehydrogenase
- E1 binds pyruvate, catalyzes decarboxylation → TPP intermediate & release CO2
- TPP intermediate reacts with the disulfide of lipoamide group on E2 → lipoamide intermediate
- E2 lipoamide intermediate carries acetyl group from E1 catalytic site to E2 catalytic site, reacts with CoA → acetyl-CoA & fully reduced dihydrolipoamide
Steps 4-5 of pyruvate dehydrogenase
- Dihydrolipoamide group swings to E3, it’s reoxidized to a disulphide. A coupled rxn forms a dithiol on E3 then transiently forms E3-FADH2
- The E3-FADH2 coenzyme intermediate is reoxidized in a coupled redox reaction producing NADH + H+
Ball and chain mechanism
E2 lipoamide picks up an acetyl group from E1 TPP
E2 can swing to bridge the gap
E2 ball and chain delivers acyl group to CoA in E2 catalytic domain
Oxidation
loss of electrons
Reduction
gain of electrons
Oxidant
compounds that oxidize other molecules
– Accept electrons
– Are reduced
Reductant
compounds that reduce other molecules
– Donate electrons
– Are oxidized
Reduction Potential (E)
Tendency for a molecule to gain electrons, driven by free energy (inverse relationship); favorable +E and -G
Using half-reactions to get ΔE
- Half-reactions can be used to determine change in reduction potential
