lecture 1

why do we use EMP glycolysis

gives intermediates and energy

why use the PPP?

costs a lot of extra ATP… but gives us NADPHs and intermediates

• also allows 7 5 and 4 C sugars to enter the pathway

• only end up with 1 pyruvate

• half ATP yield (anabolic)

why use the enter-doudoroff pathway?

allows to use gluconic acid

• we can take our time because no one else can use it

what’s to use pyruvate

1. ferment to lactate/ethanol

2. carboxylating it to oxaloacetate OAA → guconeogenesis

3. turn to alanine to send to liver

4. acetyl CoA→ TCA cycle

benefits of TCA cycle?

• 12 or so ATP

• make metabolic intermediates

costs of TCA cycle?

• generate 5 more full electron carriers → a lot of electrons need a place to go

• every time we do an electron transfer→ making a free radical is likely → lead to aging/death

when there is O2 where do we send pyruvate for TCA cycle?

mitochondria

1st step once pyruvate is in mitochondria

oxidativley decarboxylate it → acetyl CoA

where do most of our redox reactions happen and why?

mitochondria

• when we screw up → oxygen with extra electron (wants to bind to everything→ break everything→ homewrecker)

• wall off toxic reactions

mitochondrial pyruvate carrier (MPC)

carries pyruvate to the inside of mitochondria

• H+ coupled pyruvate symport

pyruvate dehydrogenase (PDH) complex

big cluster of enzymes and cofactors that catalyze decarxylation of pyruvate→ acetyl CoA and CO2

oxidative decarboxylation that happens in the mitochondria

oxidize pyruvate while removing a CO2

what happens in pyruvate → acetyl CoA in (6)

1. pyruvate goes binds to E1 where decarboxylation (CO2 is lost) and TPP binds and transfers (hydrooxyethyl derevitive)

2. electrons transferred from TPP→ oxidized lipoyllysine (S-S) → transferring pyruvate backbone to bind to S (makes acetyl lipoyllysine)

3. CoA-SH comes into E2 and binds and takes pyruvate backbone → leaves

4. lipoyllysine in reduced state (-SH HS-)

2. E3: FAD+ oxidizes reduced version of lipoyllysine

3. FADH2 transfers electrons to NAD+ → NADH + H+ leave

rate limiting step in pyruvate→ acetyl CoA

step 1: pyruvate goes to E1 → CO2 released

why is pyruvate → acetyl CoA exergonic

constantly driven forward by the release of CO2 → gas so it goes away immediately

complexes of PDH complex (3)

E1, E2, E3

a ton of E2 (attaches CoA-SH)

5 coenzymes of pyruvate dehydrogenase

1. TPP

2. lipoate

3. coenzyme A

4. FAD

5. NAD

what type of groups does coenzyme A form?

thioester acyl groups

Lipoate

coenzyme with 2 thio groups (SH) that can get oxidized to make a disulfide bond

• hydrogen carrier

• covalently linked to E2

E1

pyruvate dehydrogenase

• decarboxylating pyruvate

• 12ish subunits

dihydrolipoyl transacetylase

E2

• 50ish subunits

• transfer acetyl group to lipoic acid then acetyl CoA

dihydrolipyl dehydrogenase

E3

• 12ish subunits

• regenerates lipoic acid

substrate channeling

passage of intermediates from one enzyme directly to another enzyme without release

how is PDH complex regulated

allosterically

• NADH and acetyl CoA (negatively regulate)

cellular respiration

take pyruvate→ oxidize it all the way to water and CO2

stage 1 of respiration

oxidation of fuel to acetyl CoA

• get a little ATP and reducing equivalents

stage 2 of respiration

oxidation of acetyl groups to CO2 in the TCA cycle

• generates NADH, FADH2, and one GTP

stage 3 of respiration

electron transfer chain and oxidative phosphorylation

• generated the majority of ATP from catabolism