tsa cycle - lecture 8 and 9 COMPLETE

where is the TSA cycle found

the mitochondrial matrix

where does acetyl coa carry the acetyl group

on the thio group→ thioster group

where is acetylcoa made

end of glycolysis

end of fatty acid metabolism

end of most AA breakdown

how is acetylcoa made from the end product of glycolysis

pyruvate dehydrogenase makes AcetylCoa

whats needed ti make acetylcoa to from pyruvate

* pyruvate dehydrogenase
* O2

whats lost in the conversion of pyrubate to acetylcoa

CO2

what is made in the tsa cycel

NADH

FADH2

and a lil of ATP by substate level phosphorylation

why is the krebs cycle classified as a cycle

catabolism converges here

notjing is lost! 2C enter , 2C rerutn

many entrypoints

what can be genrated with citrate

sterols

fatty acids

what can be genrated with a ketoglutarate

glutamate

what can be genrated with glutamate

proline

arginine

purines

glutamine

what can be generated from oxoloacetate

pepwh

what can be genarted from pep

glucose/ glcine/serine/cycteine/phenylalamine/tyrosine/tryptophan

can amino acids suplly all tsa cycle componemts

most

* a ketoglutarate
* succinyl coa
* fumarate
* oxoloacetate
* acetylcoa( with oxolatet will make citrate)

where do most catabolic pathways occur

m itochondria

whats stage 2 of all catabolism

krebs cycle

where does metabolism converge

ACETYL COA - will enter tsa cycle

how much NADH made per one cycel

3h

how much fadh made per one cycle

1

how many Carbons in oxoloacete, citrate, acetyl coa

oxoloacete, 4

citrate, 6

acetyl coa 2

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where is GTP made

conversion of succinyl coa to succinate

how is acetyl fed into the TSA cycle

commbined with oxoloacetate

list all the points where nadh is made

1. isocitrate→ a ketoglutarate
2. a ketoglutarate → succinyl coA


1. malate→oxoloacetate

where is fadh made

succinate→ fumarate = FADH2

how many irreversible steps of the tsa cycle

3l

list the irreversible steps of the tsa cycle

OOA→ citrrate

isocitrate→ alpha ketoglutarate

alpha ketoglutarate → succinyl coa

EXERGONIC ENZYMES!

when are these eznymes activated

high AMP

high Ca++

what inhibts these enzumes

ATP

NADH

SuccinylCOa

what enzyme makes citrate from ooa and acetyl coa

citrate synthase

is citrate synthase responsible for an exergonic or an endergonic reaction?

exergonic

the thioester bond is high in energy!

what compound allosterically inhibits citaret synthase

citrate

what happens to acetyl coa is citarte synthase is inhibited by citrate

puhsed into fatty acid metabolism

whta compunds increases the affinity of citrate synthase for acetylcoa

oxoloacteta

what compound makes a ketoglutarate from isocitrate

isocitrate dehydrogenase

what is needed to activate isocitrate dehydrogenase

ADP

otherwise inactive

whta inhnits isocitrate dehydrogenase

ATP and NADH

how many c in alpha ketoglutarate

5

what will happen to pyrubate dehydrogenase and isocitrate dehydrogenase after a meal

* fed state= lots of ATP
* lot of pyruvate made from glycolysis→ convert to acetyl coa to make use of it by fatty acid synthesis/ other pathways
* activation of pyrubate dehydrogenase
* inhibition of isocitrate dehydrogenase by ATP will prevent TSA cycle, use those carbon skeletons for analbolism

what happens when isocitrate dehydrogenase is inactivated after a meal

* a lot of citrate was pushed into the cycel but not utilised
* citrate accumulates
* transpoet of citrate from mitochondtia to the cytosol where its used fot analbolism
* fatty acid synthesis
* acetyl coa cant move throught the membrane so citrate being made is good cuz that can be moved and the made into acetyl coa and oxoloactete , oxoloacetta can be made into pep

are there kinases/ phosphorylases in the tsa cycle?

nope

what is alpha ketoglutarate dehydrogenase

a complex of enzymes

e1,e2,e3

what is a ketoglurate dehydrogenase inhibited by

succinyl coa- its product!!!

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how is gtp made?

succil coa synthase (reversible!!) cause phosphorylysis happens

phospahte attaches to thio and the to GDP

describe the production of fadh2

succinate → fumarate

by succinate dehydrogenase (FAD gets reduced1!!!)

redox reaction! ,reversible!!

what type fo reaction is fymarase→malate

hydration

why is the productio of oxoloacetate from malate favoured?

citrate synthase= exergonic

removal of product is quickish

oxoloacette made and used by favourable reaction

favours the forward reaction

what enzyme is inhibited by citarte

phosphofructosekinase1

when is alpha keto glurate also made

transamination of glutamate

how is succinate coa made from a fatty acid metabolic intermediate

propionyl coa is made from fatyy acids

proprionyl coa→ succinyl coa

what amino acids make fumarate

phenylalamine and tyrosine

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what cycle makes fumerate

urea cycle

what amino acid makes oxoloacetta

transamination of aspartic acid

what happens th eto nadh amde in glycolysios in the skeletal muscle and the brain

* transported by the glycerol-3-phopshate shuttle
* 2atp / 1 nadh made
* 4 atps made from the 2 fadh2 generatedc

can nadh cross the inner mitochondrial membrane

no, has to be shuttled

hwo is nadh shuttled to the inner mitochondrion

using glycerophosphate shuttle!

2 e- tranferred onto DHAP by glycerophopshate dehydrogenase

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inside DHAP is oxidised, FAD is reduced

yield of 2 FADH2 taht can be utilised by Complex Q of e- transport chain

where is the malate-asparate shuttle

in the liver / kidney/ heart

how does the malate-asparatet shuttle work?

oxoloacetate is reduced to malate

malate can cross into the mitochondrial membrane

malate reduces NAD+ to yield 2NADH

2NADH inside the mitochondriom can be used to make 6ATP→ better than the glycerophopshate shuttle used in skeletal !!!

where is the nadh amde ij glycolysis

glyceraldehyde 3 phosphate dehydrogenase

G3P→ 1,3 biphosphoglycerate

what happens in the mo=itochondrion

ox phosphorylation or substarte level phopshorylation

oxidative phosphoryation

where are the electons carriers

part of the mitochondrial iner membrane

is the movemt of e- exergonic or endergonic

exergonic

what is the energy rekeqased by the transfer of e- used for?

proton pumping that drives atp synthase

what is nadh

a cofactor that was reduced byt the tranfer of e- to NAD+ from glycolitc intermediates

where are the protons pumped ?

across the inner membrane into the intermembrane space of the mitochondrion

what is free energy released by the electron transfer used for -3 things

proton pumping and Ca++ pumping and heat

how many protein complexes used in the e- transport chain

5 complexes on the inner mitochondrial membrane

what is the oxidising agent in the e- trnasport chain

o"2 is the final e- acceptors

gets reduced to water

whats complex 1 called

nadh dehydrogenasewhats

whats complex 2 called

succinate dehydrogenase

what are complex 3 and 4

cytochrome enzymes!!

why is the oiter membrane permeable

porins

what happens to nadh in complex 1

nadh dehydrogenase

nad+ made and released

how many protons pumped by complex 1

4h+

what is the force that drives atp synythase

proton motor force

where do e- from succinate pass to

Electrons from succinate pass through a flavoprotein and several Fe-S centers (in Complex II) on the way to Q

what allows the complexes to accept e- from cofactors/ succinate/ acetylcoa / G3P

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prosthertic groups

Fe3+ gets reduced to Fe2+

what is ubiquinone also called

co eznyme q

what is coQ?

electron carrier in the mitochondria

can accept one E- → becomes an intermediate

can accept two e- in total ! two step process!

can act as junctions of 2e- donor and 1e- acceptor

* like FADH2/ NADH

how are the heme cofactors joined to cyp a/b/y

not covalently

tighly bound

Fe3+

is energy needed for the electrons to flow?

no, it happens spontanously from lower E’ degree sign to higher E’ degree sign

what is the order of e- acceptors

nadh- q- CYPs- O2

what does complex 1 and 2 have in common

catalyze tramsfer of e- to ubiquinone

different e- donors!

what is the e- donor to complex 2

succinate

what is the e- donor to complex 1

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nadh

what does complex 3 catalyse

transfer of e- from ubiquinol (reduced form) to cyp c

what does complex 4 catalyse

transfer of e- from cyp c to O2wh

which complx does not pump protons

2

how many proton pumped in total

10

how is NAD+ e- tranport happen

via hydride

how does the transfer of e- happen in FAD, FMN,CoQ

via hydrogen transfer

→ FADH2

COQ QH2

what intermediate of the tsa cycle can enter the e- transport chain ?

succinate (will make fumarate in comple 2)

what are the domanisn of atp syntthase

theres 2

* f1- peripheral memnrane protein
* f0 complex of intergral membrane proteins

where is the site for adp + Pi in atp synthase

in complex f1

where are the protons pumped through

f0 complexh

how is atp made

protons cause conformational change

what is the cost of 1 atp being transported across the inner membraner

4h+

what does carbon monoxide / cyanide / sodium azide do?

block the transfer of e- onto oxegen

how does the mitochondrial dysfunction cause parkinsons

accumulation of reactive oxygen species cause mutations

how can mitochondrial dysfunction cause oncogenic events

mutation of mitochondrial allows accumulation of fumarate and succinate activate hypoxia-inductible factor →creates pseudohypoxic state → more anaerobic glycolysis → tumour growth

what enzyme muttaions cause the hif activatio

succicate dehydrogenase