Chapter 18: Preparation for the Citric Acid Cycle

cellular respiration

complete oxidation of fuel into co2 and water to generate more atp → aerobic

2 parts of cellular respiration

• citric acid cycle (aka tricarboxylic acid cyles or krebs cylce)

• oxydative phosphorylation

where does the TCA cycle occur

mitochondrial matrix

acetyl CoA

made from pyruvate under aerobic conditions → able to enter TCA cycle

• produced in mitchondria → carrier protein transports pyruvate in aerobic conditions

• 2C aceyl unit makes 2 CO2

• generates high-E electrons for atp synthesis

which enzymic complex converts pyruvate into acetyl coA

• pyruvate dehydrogenase complex → oxidatively decarboxylates pyruvate

pyruvate dehydrogenase complex: where is it found and what can it do

• found in mitochondrial matrix

• irreversible enzyme complex; 3 activities

  • oxydative decarboxylation

  • transacetylase

  • enzyme re-oxidation

why is it important that pyruavte → acetyl coA is an irreversible rxn

links glycolysis to the CAC → commits carbon atoms of carbs to oxitation by the CAC or to fatty acid synthesis

acetyl coA fate: CAC

acetyl coA goes on to support energy production by getting oxidized into CO2

acetyl coA fate: lipid synthesis

acetyl coA makes fatty acids for energy storage (usually from excess carbs)

3 enzymes of the pyruvate dehydrogenase complex

• pyruvate dehydrogenase

• dihydrolipoyl transacetylase

• dihydrolipoyl dehydrogenase

3 enzymes of the pyruvate dehydrogenase complex: pyruvate dehydrogenase

• E₁ abbreviation

• TPP prosthetic group (tight cofactor)

• rxn: oxidative decarboxylation of pyruvate

3 enzymes of the pyruvate dehydrogenase complex: dihydrolipoyl transacetylase

• E₂ abbreviation

• lipoamide prosthetic group (tight cofactor)

• rxn: transfer aceytl group to CoA

3 enzymes of the pyruvate dehydrogenase complex: dihydrolipoyl dehydrogenase

• E₃ abbreviation

• FAD prosthetic group (tight cofactor)

• rxn: regeneration of oxidized lipoamide

5 coenzymes of the pyruvate dehydrogenase complex

• 3 catalytic coenzymes (not consumed) → thiamine pyrophosphate (TPP), lipoic acid, flavin adenine dinucleotide (FAD)

• 2 stoichiometric coenzymes (consumed) → CoA and nicotinamide adenine dinucleotide (NAD+)

4 main reactions of turning pyruvate into acetyl coA

• decarboxylation

• oxidation

• transfer to CoA

• re-oxidation

4 main reactions of turning pyruvate into acetyl coA: decarboxylation

• catalyzed by E₁ (pyruvate dehydrogenase)

• pyruvate combines with ionized TPP (carbanion form; coenzyme), then decarboxylated (CO2 release) to form hydroxyethyl-TPP

• rate limiting step

lipoamide vs lipoic acid

lipoamide is a derivative of lipoic acid

4 main reactions of turning pyruvate into acetyl coA: oxidation

• catalyzed by E₁ (pyruvate dehydrogenase)

• hydroxyethyl-TPP oxidized to acetyl while being transfered to lipoamide (coenzyme) of E₂ → prduces acetyl-lipoamide w energy rich thioester bond

• disulfide of lipoamide reduces into disulfhydrl form

4 main reactions of turning pyruvate into acetyl coA: transfer to CoA

• catalyzed by E₂ (dihydrolipoyl transacetylase)

• acetyl of acetyl-lipoamide transfer to CoA (coenzyme)→ produces acetyl coA and dihydrolipoamide

• thioester bond preserved

what structural feature and specific amino acid residue anchor the lipoamide cofactor in step 3 (transfer to coA)

• lipoamide cofactor is attached to a lysine residue on the E2 enzyme → creates flexible swinging arm

• arm reaches into E1's to get acetyl group, swings it over to E2's to make Acetyl-CoA, then resets at E₃

riboflavin of FAD aka

vitamin B12

niacin of NAD aka

vitamin B3

4 main reactions of turning pyruvate into acetyl coA: reoxidation

• catalyzed by E₃ (dihydrolipoamide dehydrogenase)

• dihydrolipoamide oxidized to lipoamide using FAD → produces FADH2 resets lipoamide

• FADH2 oxidixed by NAD+

4 main reactions of turning pyruvate into acetyl coA: reoxidation → how is FADH2 able to transfer e^- to NAD

usually FAD recieves from NADH, but the electonr transfer potential of FAD increases when it associates with E₃

flavoproteins

• proteins tighly associated with FAD

• involved in redox rxns

why is it efficient that the 3 enzymes of the pyruvate dehydrogenase complex are close to each other

increases overall rxn rate, minimizes side rxns, and coordinates catalysis

what inhibits pyruvate oxidation into acetyl coA

• high [ ] of NADH and acetyl CoA → energy needs met/enough acetyl CoA and NADH were produced from fatty acid degradation

  • acetyl coA inhibits transacetylase component (E₂)

  • NADH inhibits dihydroliopyl dehydrogenase (E₃)

• pyruvate dehydrogenase kinase phosphorylates pyruvate dehydrogenase (E1) → off

• high ATP

result → spares glucose

what turns the phosphorylated pyruvate dehydrogenase (E1) back on

• ADP and pyruvate inhibit pyruvate dehyrdrogenase kinase

• pyruvate dehydrogenase phosphotase stimulated by insulin (fed state from liver) or Ca2+ (from contraction) → pyruvate dehydrogenase on → pyruvate converts into acetyl CoA