Lesson 13 - Pyruvate Dehydrogenase Complex (PDC) and the Citric Cycle (TCA) Flashcards
is a central area of metabolism
a process where anabolic and catabolic pathways intersect
TCA:
intersection of amino acid, fatty acid and carbohydrate metabolism
considering the structure of pyruvate (C3H3COO3-), how does pyruvate get into the mitochondrion
a mitochondrial pyruvate carrier
how does the structure of the mitochondrion facilitate the exchange of metabolites betwween the TCA and ETC
IM is embedded with components of the ETC
– reduced coenzymes are “fed” directly in
predict what the most importnat produts are that are directly produced from glycolysis and the citric acid cycle
e-‘s in the form of reduced coenzymes
how does the cell harness (conserve) potential energy through these processes to synthesis ATP during oxidative phosphorilation
- the free energy of electron transfer from NADH –> H2O is conserved in a H+ gradient across the IM
pyruvate dehydrogenase complex, PDC, an example of a multienzyme complex:
1 - two or more noncovalently associated enxymes
2 - catalyze sequential reactions
3 - increase the frequency of collisions and overall reaction rate (free enzymes very close together)
4 - place a series of reactions rate coordinate control (allosteric molecule)
requires 5 cofactors (mostly from diet)
1 - coenzyme A (CoA or CoA-SH)
2 - Lipoamide
3 - TPP
4 - NAD+
5 - FAD
where does NAD come from
dietary Niacin (vitamin B3)
- sever niacin deficiency causes the disease pellagra
symptopms include skin rahs, diarrhea, and neurological problems
vitamin b missing in a corn rich diet
^^^ present in corn, but in the form of a protein bound form (NAD+/NADH) that drastically reduces its absorption in the intestine
- soaking corn in lime solution (calcium oxide) releases niacin from it’s protein-bound form
where does FAD come from
- dietary riboflavin
where does CoA come from
- derived from dietary pantothenic acid
where does TPP come from
dietary thiamine
- polished rice is deficient in thiamine
- whole rice is rich in thiamine
dietary lipoic acid is covalently attached to
- a Lys residue on E2 –> involved in a group transfer reaction
Reaction 1: to get the acetyl-CoA
pyruvate + NAD+ + CoA –> acetyl-CoA + NADH + CO2
by pyruvate dehydrogenase complex (E1 + E2 + E3)
what kind of molecule is Acetyl-CoA
thioester; “high energy” –> FAR from equilibrium
what type of reaction is reaction 1
group transfer
- pyruvate reacts with the TPP carbination of E1 to form an addition product that undergoes decarboxylation giving hydroxyethyl-TPP
what type of reaction is rxn 2
group transfer
- the hydroxyethyl group is transferred by E1 to a lipoamide swinging arm on E2 resulting in oxidation of the 2-carbon fragment to an acetyl group and reduction of the lipoamide disulfide to dihydrolipoamide (with actyl group bound)
for reaction 3 does the lipoamide emerge from this reaction fully oxidixed or reduced
fully reduced
does NAD+ emerge from rxn 4&5 in the oxidized or reduced state
reduced?
rxn 1
acetyl-CoA + oxaloacetate + H2O –> CoA + Citrate
by citrate synthase
- irreversible under cellular conditions, delta G negative
rxn 2
citrate <–> isocitrate
by aconitase
rxn 3
isocitrate + NAD+ –> alpha ketoglutarate + NADH + CO2 + H+
by isocitrate dehydrogenase
– oxidative decarboxylation, NADH + H+ generated
rxn 4
alpha ketoglutarate + CoA + NAD+ –> Succinyl - CoA + NADH + CO2 + H+
by alpha ketoglutarate dehydrogenase
– mechanistically identical to PDC
rxn 5
succinyl - CoA + GDP + Pi <–> succinate + GTP + CoA
by succinyl-CoA synthetase
– energy of thioester bond hydrolysis
- conserved in substrate level phosphrylation
rxn 6
succinate + FAD <–> Furmarate + FADH2
by succinate dehydrogenase
– AKA complex II of the ETC
– located in IM NOT MATRIC; FADH2 produced
rxn 7
fumarate + H2O <–> malate
fumarase
– stepwise addition of H2O across double bond
rxn 8
malate + NAD+ <–> Oxaloacetate + NADH + H+
what reactions are the far equilibrium rxns
1,3,4
TCA net equation
acetyle-CoA + 3 NAD + FAD + GDP + P + 2H2O –> CoA-SH + 3NADH + FADH2 + 3H+ + GTP + 2CO2
reduced coenzymes funneled into ETC …
ultimately produce significant ATP
+ NAD+, CoA, ADP, Ca 2+ indicates
that the cell needs to make ATP, low energy charge (EC); catabolize glucose to synthesize ATP
what are the targets of regulation in PDC and TCA
far from equilibrium rxns
- NADH, ATP indicate
cellls have an ample ATP, high energy charge (EC); store glucose, don’t catabolize
