TCA cycle and Oxidative Phosphorylation

in the cytosol

Under aerobic conditions, glucose is metabolized into pyruvate where in the cell

must go into the mitochondria

In order for pyruvate to be oxidized into acetyl CoA and CO2, where must it go?

in the mitochondrial matrix

Where can NADH be oxidized

through pyruvate dehydrogenase complex

turns NAD+ into NADH

releases CO2

ONLY OCCURS WHEN OXYGEN IS PRESENT

Through which enzyme is pyruvate turned into acetyl CoA

by pyruvate carboxylase

REQUIRES ATP and CO2

anaplerotic reaction

How is pyruvate turned into oxaloacetate

through pyruvate proton symporter

How is pyruvate transported to the mitochondrial matrix?

in the inner mitochondrial matrix

Where is PDHC localized

oxidative decarboxylation

Pyruvate undergoes _________________ to form acetyl coa

2 CO2

2 NADH

What are the products that form when pyruvate is decarboxylized to form acetyl coa

acetyl coa is a 2 carbon molecule

how many carbons is in acetyl CoA

LIPOIC ACID = NOT WATER SOLUABLE

4 WATER SOLUBLE VITAMINS

B1 thiamin

B2 riboflavin

B3 niacin

B5 pantothenic acid

The pyruvate dehydrogenase complex is dependent on what coenzymes?

3 with respective prosthetic groups

How many enzymes are a part of the PDHC

pyruvate dehydrogenase with THIAMIN-PPi

what is the first enzyme and prosthetic group of PDHC

dihydrolipoyl transactylase with LIPOIC ACID and Coenzyme A (CoA-SH)

what is the second enzyme and prosthetic group of PDHC

dihydrolipoyl dehydrogenase

with prothetic group = FAD &

coenzyme = NAD+

what is the third enzyme and prosthetic group of PDHC

exergonic and thermodynamically favored

What type of reaction is the hydrolysis of acetyl-CoA

B5 pantothenic acid

CoASH contains which one of the four water soluable coenzymes

by allosteric effectors and covalent modification

how does regulation of PDH occur

NADH and acetyl coa has a feedback inhibitory effect on PDH

how is PDH allosterically regulated

it is active by phosphatase

What happens when PDH is in the dephosphorylated form

inactivated by PDH kinase

What happens when PDH is in the phosphorylated form

it increases PDH phosphatase activity to dephosphorylze and activate PDH

What does insulin do to PDH activity

accumulation of pyruvic and lactic acid that leads to congenital lactic acidosis

NEURODEGENRATION

MUSCLE SPASTICITY

if there is poor absorption of thiamin or alpha subunits in PDH1 what is the result

arsenite and mercuric ions inhibits ezyme and leads to neurodegeneration and muscle spascity

What happens when transacetylase enzyme of PDH reacts with SH groups of lipoic acid

oxidation of he acetyl moiety of acetyl coa to CO2

What is the specific oxidation step of TCA cycle

reduction of coenzymes NAD+ and FAD

What is the specific reduction step of TCA cycle

in the mitochondrial matrix

Where are the TCA cycle enzymes localized

inner mitochondrial membrane

Where is the enzyme succinate dehydrogenase localized

3 NADH

1 FADH2

2 CO2

How many energy substrates does the TCA cycle release, one acetyl-coa makes

citrate is a sour substrate for metabolic oxidation

What is the mnemonic for TCA cycle

aceyl- citroyl-CoA being hydrolyzed to form citrate by CITRATE SYNTHASE

What step in the TCA cycle is highly exergonic?

isocitrate

through isocitrate dehydrogenase releases NADH

and makes alpha-ketogluterate

release NADH and CO2

What is the first step that releases NADH and CO2

alpha-ketogluterate acted on by

alpha-ketogluterate dehydrogenase

releasing NADH and CO2

adding CoA-SH

inhibited by Arsenite

BEHAVES SIMILAR TO PDH

What is the next step that releases NADH and CO2

when succinyl-CoA is made into

SUCCINATE by

succinate thiokinase known as succinyl-CoA

forms ATP

At what step does substrate level phosphorylation occur

succinate to fumarate

using succinate dehydrogenase

inhibited by malonate

What step of TCA cycle requires the enzyme thats in the inner mitro membrane

l-malate to oxaloacetate by malate dehydrogenase

What is the third and last step of the TCA cycle that produces NADH

formation of oxaloacetate from l-malae by malate dehydrogenase

What reaction of the TCA cycle is endergonic

succinate to fumarate by SDH

what step forms FADH2 in the TCA cycle

pyruvate dehydrogenase complex

the alpha-ketoluterate dehydrogenase process uses the same coenzymes and prothestic group as

10 ATP

how many ATP produced from one turn of TCA cycle

3

how many NADH produced from one turn of TCA cycle

1

how many FADH produced from one turn of TCA cycle

2.5 ATP

How many ATP is produced once NADH undergoes the ETC

1.5 ATP

How many ATP formed when FADH undergoes the ETC cycle

2

how many atp formed from glucose to pyruvate

32 atp

What is the total number of atp through two turns of TCA cycle

if glycerol is at play then how many ATP does the tca cycle make 30

PDH

citrate synthae

isocitrate dehydrogenase

a-ketogluterate

What are the main sites of TCA regulation

substrate availability

allosteric regulation

What are the two types of regulation in the TCA cycle

oxidized cofactors such as NAD FAD and ADP

the TCa cycle cannot take place without its availability

Define how the availability of substrates regulates the TCA cycle

allosteric INHIBITION of citrate synthase by ATP

allosteric ACTIVATION of isocitrate dehydrogenase by ADP/ INHIBITION BY ATP AND NADH

regulation of a-KGDH similar to PDH

Give examples of allosteric regulation in the TCA cycle

pheochromocytoma, gastro tumors, renal cancer

What is the clinical significance of dysregulated TCA with mutations in the gene encoding SDH complex

renal cell carcinoma

What is the clinical significance of dysregulated TCA with mutations in the gene encoding fumarase

in the inner mitrochondrial membrane produces ATP

Where is the ETC localized during the oxidative phosphorylation cycle to produce

NADH and FADH2

What two molecules go throught the ETC

O2 is the final acceptor of electrons

Why do we call the ETC the respiratory chain?

C6H12O6 + 6O2 → 6CO2 + 6H2O

What is the important reaction of glucose from glycolysis all the way to the electron transport chain and oxidative phosphorylation?

hydride ion forms

What form of electrons does NAD+ accept

two hydrogen atoms

What form of electrons does FADH2 accept

6 steps

4 complexes

Name the complexes of the ETC clycle

Complex I —> 4

Complex III —> 4

Complex IV—> 2

NADH specific = 10 H+

FADH pumps 6 H+

Complex II —> 4

Complex IV —> 2

Which complexes pump hydrogen atoms and how many

3 complaxes

I, III, IV

How is NADH oxidized?

complex II

Q

Complex III

Cyt c

Complex IV

how is FADH2 oxidized

known as mobile carrier

carries 2 electrons

diffuses rapidly within the membrane

What does the Coenzyme Q do and what else is it known as

carries one electron

soluble protein

What does cytochrome C do CYT c

have iron-sulfur proteins non-heme iron protein fe-s

What do the first three complexes have in common

CYT

C

A

A3

What are the three types of heme-proteins

iron can be bound to the sulfur within the cysteine groups

iron can be directly bound to sulfur atoms and bound to sulfur within cysteine groups

What are the two ways iron-sulfur proteins be bonded

FADH going into Complex II

which complex of ETC has no proton flow

ATP synthase powered by the proton gradient

Complex 5 known as ATP synthase, functions as rotary motor

ETC coupled to ATP synthesis

What is the chemiosmotic theory

two

F0

F1

How many parts does complex 5 have

C subunit:

proton channel, when protons pass through it rotates

gamma subunit

functions as a bent axle

when it rotates, causes conformational changes in beta subunits of F1

F0 EMBEDDING IN THE MEMBRANE

How many subunits does F0 have and what does it do?

3 beta subunits that go through confirmational change and create ATP

3 alpha subunits

Describe the F1 subunit

Adenine nucleo and PHOSPHATE transported into mitro

ATP transported out

in the beta subunits of F1 ADP3—>ATP4—>ATP

second transporter: transports Pi and H+

what does the phophate and Adenine Nucleotide transporter do?

malonate acts as an competitive inhibitor

binds to the active site of SDH

What inhibits complex 2

inhibited by antimycin A

What inhibits complex 3

amobarbital barbiturate

What inhibits complex CoQ

inhibitors:

Cyanide (CN-)

Carbon monoxide (CO)

Hydrogen sulfide (H2S)

What inhibits complex 4

oligomycin

This blocks proton flow through ATP synthase, thus inhibiting oxidation and phosphorylation.

uncouplers

UCP1 in newborns

2,4 dinitrophenol

These cause the inner membrane of the mitochondria to be permeable to protons. ruining the gradient. Now energy is not being used to make ATP so this energy is lost as heat.

IN THE BRAIN 30 ATP

requires NADH cannot pass through membrane

reduced to G3P to dihydroxyacetone phosphate to charge FAD to FADH2 in inner membrane

how does glyerophosphate transfer reducing equivalents to mitro

IN THE CARDIAC MUSCLE 32 ATP

malate made because NADH cant pass

a-ketoglutarate made because oxaloacetate unable to cross membrane

how does the malate shuttle transfer reducing equivalents to mitro matrix

made when one 1 diatomic oxygen is in the ETC

very detrimental

superoxide creates hydrogen peroxide

GLUTHATHIONE PEROXIDASE decomposes hydrogen peroxide ito H2O and O2

makes GSSG which is need for PPP

gluthathione reductase oxidized NADPH

Where is superoxide made and what is its main function