biochem citric acid cycle

aerobic fate of pyruvate

• cellular resipiration

• diffuses through outer membrane of mitochondria

• pyruvate translocase symport (proton and pyruvate) take them past inner membrane into matrix

• this is where it will be converted into acetyl coa and acetyl coa can enter the citric acid cycle

pre step of citric acid cycle

• oxidative decarboxylation of pyruvate into acetyl coA

• catalyzed by pyruvate dehydrogenase complex

  • requires 5 coenzymes

  • trimer

• irrversible

postethic groups of PDC

TPP, lipolysine, and FAD (always on enzyme complex)

co substrates of PDH

• NAD+ and COA-SH (has a thioester bond)

• not permanent to PDH

  • associate, do function, leave

Coenzyme A

• carries acetyl groups

• structure

  • reactive thiol group, panthothemic acid (linker), modified ADP (phosphate on 3 carbon)

• also plays roles in the oxidation of fatty acids and the synthesis of lipids

• vitamin B precursor

Lipoic acid (one of the prosthetic groups)

• covalently linked to enzyme with lysine residue

• oxidized form has a disulfide bond in the head group

• carrier of hydrogen and acetyl group

• NO vitamin precursor

TPP

• most active part due to active proton on C2

  • cleaves bonds to transfer aldehyde group

• vitamin b precursor

PDC

• E1 (pyruvate dehydrogenase)

  • 24 chains

  • TPP

• E2 (dihydrolipoyl transacetylase)

  • 24 chains

  • lipoamide

    • has multiple binding domains

  • long chain that moves

• E3 (dihydrolipoyl dehydrogenase)

  • 12 chains

  • FAD

• 60 total chains

• E1 and E3 surround E2

Advantages of PDC being a multiple enzyme complex

• substrate channeling

  • intermediates go directly from one active site to the next

  • minimizes side reactions and increases rate of reaction

• coordinated regulation

  • regulation of one subunit affects activity of everything

making acetyl coA step 1

• decarboxylation

• rate limiting step

• carbon 1 is lost and TPP gains carbon and 2 protons

  • TPP takes it (E1)

making acetyl coA step 2

• oxidation to form the acetyl group

• thioester bond is created with lipoamide

  • E2

  • lipoamide took carbon from TPP and TPP is reset

making acetyl coA step 3

• acetyl group is transferred to CoA

  • thioester bond is preserved

  • on E2

• at E3

  • lipoamide is oxidized and reset with FAD reduction

  • FADH2 is reset by NAD+ which takes the two protons and restores FAD

T or F: E1-3 are all trimers

F: E1 is a tetramer made of alpha beta dimers, E2 is a trimer of all alpha chains, E3 is a dimer of alpha and beta chains (the PDC is a trimer)

T or F: the E2 lipoamide region is high in prolines

F; high in alanines