Pyruvate Oxidation Flashcards
Pyruvate Oxidation
Links Glycolysis to TCA cycle
- remember pyruvate has 3 fates:
- under Aerobic conditions
- occurs in the matrix of the mitochondria
- irreversible reaction
- catalyzed by the enzyme pyruvate Dehydrogenase and produces CO2 and captures High Transfer Potential electrons in the form of NADH
Pyruvate Dehydrogenase
Multienzyme complex
Composed of 3 Prosthetic Groups/2Coenzymes
Overall process preserves free energy of decarboxylation
-Free energy used to reduce NAD+ to NADH and to attach acetyl group to CoA forming Acetyl-CoA
- E1=pyruvate dehydrogenase
- E2= dihydrolipoyl transacetylase
- E3= dihydrolipoyl dehydrogenase
Thiamine Pyrophosphate
TPP -Prosthetic Grup (E2) Function-Aldehyde group carrier -Thiamine (B1) vitamin precursor -Deficiency-Beriberi
Lipioc Acid
(Lipoamide)
- Prosthetic group (E2)-attaches to R group of Lysine
- Function-acyl group carrier
- Lipoid acid is vitamin precursor
Pyruvate Dehydrogenase (E1)
- Reaction Type
- Helper Molecules
- Regulation
Reaction Type:
-Decarboxylation
-oxidation/reduction
OR Oxidative decarboxylation of pyruvate
Helper Molecules
-Prosthetic Groups-Thiamine Pyrophosphate (TPP)
TPP Carbanion + Pyruvate-> Hydroxyethyl-TPP + CO2
Dihydrolipoyl Transcetylase (E2)
- Reaction Type
- Helper Molecules
- Regulation
Reaction Type:
-Transfer of acetyl group to CoA
Helper Molecules:
- Prosthetic group- Lipoic acid (lipoamide)
- Coenzyme-CoA
REGULATION:
Inhibited BY Acetyl CoA
CoA + Acetyellipoamide-> Acetyl-CoA + Dihydrolipoamide
Dihydrolipoyl dehydrogenase (E3)
- Reaction Type
- Helper Molecules
- Regulation
Reaction type:
- oxidation of dihydrolipoamide/reduction of FADH2
- regeneration of oxidized form of Lipoamide
Helper Molecules:
- Prosthetic group-FAD
- Coenzyme-NAD+
Regulation:
Inhibited by NADH
Dihydrolipoamide+ FAD-> Lipoamide + FADH2-> (ADD NAD+) FAD + NADH + H+
Regulation of Pyruvate Dehydrogenase
Activated/stimulated by Dephosphorylation
Inactived/Inhibited by Phosphorylation
Allosteric regulators:
Stimulators:
-ADP
-Pyruvate
Inhibitors:
- ATP
- acetyl-CoA
- NADH
Synonyms for Citric Acid Cycle
Citric Acid Cycle
TCA Cycle (Tricarboxylic cycle)
Acetyl CoA-> CO2
Krebs Cycle
Where does the citric acid cycle occur?
Matrix of Mitochondria
Citrate Synthase Rxn
Citric Acid Cycle
Acetyl-CoA(2C) + Oxaloacetate(4C) -> Citrate (6C) + CoA
Rxn Type:
Aldol Condensation followed by Hydrolysis after intermediate
Intermediate: Citryl CoA
Helper Molecules: No
Regulated YES Allosteric: Stimulated: -Ca2+ -ADP Inhibited: -ATP -NADH -Succinyl CoA -Fatty Acyl CoA
Citrate Synthase Enzyme
Dimer
Sequential Order kinetics:
1) OAA binds (2 binding sites)
2) Acetyl CoA Binds
Minimizes Side Reactions by:
- ordered binding
- catalytic residues crucial for hydrolysis of the thioester linkage are not in correct position until Intermediate is formed (Citryl CoA)
Aconitase Rxn
Citric Acid Cycle
Citrate-> cis-Aconitate-> Isocitrate Reaction Type: Dehydration followed by hydration -Isomerization Int: cis-Aconitate Helper Molecules NO
Regulated NO
BUT is inhibited by fluoroacetate
- rat poision
- fluoroacetate is converted for Fluoroacetyl-CoA, which condenses with oxaloacetate to form fluoroisocitrate which is an inhibitor of aconitase and citrate accumulates
Aconitase Enzyme
Iron Sulfur protein OR Nonheme Iron Protein
Composed of 4 Fe (iron) complexed to:
- 3 cysteine sulfurs
- 4 inorganic sulfides
1 Fe binds to Citrate by Carboxyl (COO-) and Hydroxyl (OH-)
Isocitrate Dehydrogenase Rxn
Citric Acid Cycle
Isocitrate-> Oxalosuccinate–> Alpha Ketogluterate + CO2
Reaction Type: Oxidative decarboxylation -NADH produced -CO2 produced (after intermediate) Helper Molecules:NONE
Regulated YES Allosteric: Stimulated: ADP Ca2+
Inhibited:
ATP
NADH