EXAM 2 Flashcards
what are different ways we can generate acetyl CoA
Carbohydrates
Fatty Acids
Amino Acids
Acetyl CoA ____ in the TCA cycle, where intermediates are utilized in a _________ _________
oxidized, circular pathway
what is the primary determinant in fate of pyruvate in humans?
O2 levels
what is the most important molecule that fuels the TCA cycle
acetyl CoA
Draw Acetyl CoA
slide 3 on PDHC
Glycolysis occurs in ______ and does not require ______
cytoplasm, oxygen
Glycolysis generates a net of how many ATP and how many pyruvates?
2 ATP , 2 Pyruvate
TCA cycle allows for _______ of _______ to _____ under _____ conditions
oxidation, pyruvate, CO2, aerobic
where does the TCA cycle occur
mitochondrial matrix
electron movement of the ETC is couple with
the pumping of H+ aka PMF creating a large H+ gradient
what needs to occur before fueling TCA
pyruvate is converted to acetyl-CoA
What is occuring in the TCA (general)
acetyl-coA oxidized to CO2 and electrons are stored as NADH and FADH2
Since electrons are stored as NADH and FADH2 where do they go ?
ETC
What is the final electron acceptor of ETC
Oxygen
what drives synthesis of ATP of TCA and what is this process known as
coupling of proton gradient across the membrane with electrons , known as oxidative phosphorylation
Characteristics of Inner mitochondrial membrane
impermeable to almost everything
why is it important for the IMM to be impermeable to almost everything
it allows for moving of e- in a spont. direction to utilize the energy to force the pumping of e- against [ ] gradient creating an increase of proton gradient b/w IMM and matrix
what is the ultimate fate of the carbons from the glucose that fuels glycolysis
CO2 as a waste product
complete oxidation of glucose to CO2 involves removal of how many electrons? what does this mean?
24 e-, means that process is a 24 e- rich oxidation
how many total electrons are produced in glycolysis
4
how many total electrons are produced by PDHC
4
How many electrons are produced for each acetyl CoA in TCA
8
what molecules are used to fuel oxidative phosphorylation
NADH and FADH2
How many electrons does NADH always transfer at a time
2 e-
Draw the mechanism for the oxidation of NADH
slide 10 on PDHC
draw the mechanism for the reduction of NAD+
slide 10 on PDHC
Draw FAD
SLIDE 20 on PDHC
why can flavin coenzymes participate in SET or 2 e- transfer rxns
it can exist in three oxidation states
why do we prefer 2 e- transfer rxns over SET in flavin coenzymes
because SET form radicals which are highly reactive and can react with anything they touch
from what vitamin do we get FADH2
riboflavin
what is the source of acetyl CoA
pyruvate
what enzyme is able to covert pyruvate to acetyl-CoA
Pyruvate Dehydrogenase Complex
outer mitochondrial membrane is permeable to
anything smaller than 5 kD
since the IMM is highly impermeable what are the only molecules it permeable to
O2, H2O, CO2
In order for pyruvate to come into the matrix what must it use
transport protein known as pyruvate/H+ symporter
define Pyruvate/H+ symporter
movement of H+ and Pyruvate in the same direction into the matrix
what are the three enzymes that make up the PDHC
Pyruvate DH (E1)
Dihydrolipoyl transacetylase (E2)
dihydrolipoyl DH (E3)
Draw TPP
slide 20 on PDHC
Draw CoA
slide 20 on PDHC
Draw Lipoic Acid
slide 20 on PDHC
function of CoA
carrier of acetyl and other acyl groups
accepts acetyl group from Lipoamide
T/F PDHC is irreversible and therefore regulated
T
draw out the diagram that summarizes the PDHC reactions
slide 21 on PDHC
function and location of TPP
E1, Decarboxylates pyruvate yielding a hydroxyethyl TPP carbanion
function of lipoamide
swinging arm to facilitate redox chemistry
function of NAD+ in PDHC
mobile e- carrier
T/F CoA serves to generate a thioester bond with energy roughly = to ATP
T
Beriberi is caused by
TPP/Vitamin B1(Thiamine) deficiency
symptoms of beriberi
pain
paralysis
wasting
heart failure
who are susceptible to beriberi
ppl who eat only white rice
alcoholics
what does the energy of thioester of CoA roughly equivalent to in energy terms
ATP
why would alcoholics be deficient in TPP
absorption
storage
metabolism
activation of many vitamins
location and function of lipoic acid
covalently linked to a Lys residue on E2, accepts the hydroxyethyl carbanion from TPP as an acetyl group
FAD location and function in PDHC
E3, reduced by lipoamide
disadvantages of FADH2
not a mobile e- carrier it is associated with an enzyme
function of FADH2 in PDHC
transfers e- to NAD+ forming NADH
Propose a mechanism for dihydrolipoyl DH ( Draw FADH2 and NAD+)
look at journal
Equation for electrochemical potential, identify which is the chemical and which is the electrical potential
∆G’ = RTln ([A destination]/[A source]) + (ZF(Membranepotential))
first half is chemical
second half is electrical
what is the importance of pyruvate/H+ symporter
ATP synthesis
Retrograde signalin
Quality Control System
Anion outward transport and Cation inward transport
Why so we care about membrane potential
long lasting drop or rise of normal levels may induce unwanted loss of cell viability and cause pathologies
role of mitochondrial membrane potential
- factor in selection of nonfunctional mitochondria
- drives inward transport of cations and outward transport of anions
- reestablishing of membrane potential
- want to trigger apoptosis in case of heterogeneity of membrane potential that may be a sign of pathology
entry of new carbon units into the TCA cycle is from ?
pyruvate or oxidation of FAs
Transfer of the 2-C acetyl-CoA to 4-C OAA yields
citrate
what kind of rearrangement yields isocitrate
the movement of 1 -OH group down on carbon
two successive decarboxylation of TCA produce
a-KG and then succinyl-CoA
T/F multiple rearrangements need to take place in TCA in order for regeneration of OAA
T
What is the first metabolite produced in TCA
Citrate
What is the last intermediate produced in TCA
Oxaloacetate
what is the enzyme that is considered the first reaction wher 2-C units of acetyl CoA are introduced to TCA by addition of 4C unit OAA to form citrate
citrate synthase
citrate synthase is classic chemistry of what molecule
CoA
Describe the citrate Synthase mechansim
- Ca of acetyl group in acetyl CoA is acidic and can be deprotonated to form carbanion
- then carbanion does nucleophilic attact on a-carbonyl of OAA
- Intermediate citryl-CoA is produced
- Thioester hydrolysis produce citrate
what enzyme of TCA undergoes a thioester hydrolysis
Citrate synthase
Function of citrate synthase
reaction that initiates TCA and produces citrate from OAA and acetyl-CoA
what enzyme mechanism of TCA cycle can be best described by an isomerization reaction that utilizes water for net conversion of tertiary alcohol to secondary alcohol
Aconitase
aconitase function
isomerizes citrate to yield isocitrate which can be oxidized
what enzymes use an iron sulfur cluster to dictate stereospecificity
aconitase
succinate DH
function of iron-sulfer cluster
aids in stereochemistry specificity of enzymatic reactions
facilitates redox rxn and transfer of e-
serve as e- carriers of complexes in ETC
what enzyme contains cis-aconitate intermediate in their mechanism
Aconitase
why is it important for citrate to undergo a change in stereochemistry
need for a-KGDH rxn to occur
function of isocitrate DH
first link to the ETC because it is where first NADH is produce
which enzyme mechanism contains oxalosuccinate as an intermediate
Isocitrate DH
Describe the mechanism of Isocitrate DH
- first their is oxidation of C2 OH of isocitrate to form oxalosuccinate
- then a b-decarboxylation rxn to expel the CO2 group
what enzyme mechanism is a classic NAD+ chemistry that involves hydride removal followed by decarboxylation
Isocitrate DH
Where does the CO2 release com form the enzyme mechanism of Isocitrate DH
OXAL
what enzyme catalyzes the second oxidative decarboxylation of TCA
a-ketoglutarate DH complex
what enzyme does a-ketogluterate DH Complex most resemble
PDHC
What are the 5 coenzymes/cofactors used in aKDHC
TPP
CoASH
Lipoic acid
NAD+
FAD
What are the enzymes that make up the aKDHC
a-ketoglutarate DH
dihydrolipoyl transsuccinylase
dihydrolipoyl DH
where is the second NADH produced
a-KDHC
if you replace the top two carbons of aKetoglutarate wht will happen
it will form pyruvate
function of aKDH and location
oxidative decarboxylation , E1
Function of dihydrolipoyl transuccinlyase and location
transfer of succinyl group, E2
Function of dihydrolipoyl DH in aKDHC and location
regenerate lipoamide , E3
what enzyme harvest high energy thioester bond to make GTP which later makes ATP
Succinyl-CoA synthetase
T/F succinyl-CoA is symmetric and therefor we can no longer distinguish which carbons came from acetyl-CoA
F, it is succinate
how would you categorize the reaction/mechanism of succinyl-CoA synthetase
substrate level phosphorylation
what enzyme mechanism is driven by hydrolysis of CoA ester
Succinyl-CoA synthetase
T/F Citrate is a great substrate for oxidation
F, it is a poor substrate
what enzyme produces the first NADH of the TCA
Isocitrate DH
where is the second NADH produces in the TCA
aKGDHC
why can we no longer distinguish which carbons came from acetyl-CoA in succinate
it is a symmetric molecule
what enzyme mechanism involves the formation of a phosphohistidine to produce succinate
Succinyl-CoA synthetase
what enzyme produces a nucleotide triphosphate in TCA
Succinyl-CoA Synthetase
what are disadvantages of FADH2
not mobile e- carrier
produces less ATP than NADH
what enzyme produces an FADH2
Succinate Dehydrogenase
how do you calculate standard free energy given reduction potentials
∆G’ = -nF(∆E’)
where n represents number of e- transferred
How do you calculate ∆E’
E’(acceptor) - E’ (donor)
name the enzyme in which the mechanism involves a hydride removal by FAD
Succinate DH
What enzyme of TCA is also part of the ETC , specifically Complex II, found in the IMM
Succinate DH
the e- transferred from succinate to FAD ( to form FADH2) are passed directly to …… ? in order to get to the ETC
Ubiquinone
List the enzymes that are fully reversible in TCA cycle and are utilized for the rearrangement of carbon skeletons
Fumarase
Malate DH
What enzyme mechanism uses water to rearrange its carbon skeletons and form malate
Fumarase
T/F the actual mechanism for fumarase is known
F, it is not known for certain
In a proposed enzyme mechanism of Fumarase what is the intermediate formed before it becomes malate
carbanion
malate gets oxidized or reduces to form Oxaloacetate?
Oxidized
what enzyme mechanism is classified as an NAD+- dependent oxidation reaction
Malate DH
In the Malate DH reaction, what carbond gets oxidized
the one that received an OH group from the previous reaction done by Fumarase
describe the mechanism for malate DH
H of OH group on malate attacks NAD+ and O group forms double bond letting the another H leave forming OAA and NADH
what are the substrates for citrate synthase
oxaloacetate and acetyl coA
Name the two allosteric regulators of Pyruvate DH ( not talking about covalen modification)
NADH and Acetyl CoA
if both NADH and Acetyl CoA levels are low how does this affect PDH?
It will be active
draw a simple diagram of how PDHC is covalenty modified
slide 9 on Regulation
what are the two ways we can covalently modify PDHC
Pyruvate DH kinase
Pyruvate DH phoshpatase
what activates Pyruvate DH kinase and how does this affect PDHC
high levels of NADH, Acetyl CoA, and ATP
PDHC will be inactivated
what is the mode of action that Pyruvate DH kinase is being regulated
Serine Residue of E1-PDH Phosphorylate, bound to complex
what inhibits Pyruvate DH kinase and how does this affect PDHC
high levels of pyruvate , NAD+, Ca2+, and ADP
PDHC complex on
What activates pyruvate dehydrogenase phosphatase and how does this affect the PDHC
high levels of Ca2+, pyruvate, NAD+, ADP, and insulin
PDHC is on
What inhibits pyruvate dehydrogenase phosphatase and how does this affect the PDHC
high levels of ATP, NADH, and acetyl-CoA
PDHC is off
what covalent modification enzyme blocks the decarboxylation of pyruvate and halts the formation of acetyl-CoA
Pyruvate DH Kinase
How does the pyruvate DH phosphatase activate PDHC
hydrolyzes the phosphorylated serine of E1 by using calcium to bind to the complex ( without it , it won’t be able to associate with the complex)
T/F PDHC is covalently regulated by allosterically controlled enzymes
T
in terms of TCA enzymes, what is inhibited by high levels of NADH
PDHC, Citrate-Synthase, aKGDHC
what complex is inhibited by high levels Acetyl-CoA
PDHC
in terms of TCA enzymes, what is inhibited by high levels of citrate
citrate synthase
NOTE: also inhibits glycolytic enzyme PFK1
in terms of TCA enzymes, what is inhibited by high levels of high levels of Succinyl CoA
Citrate synthase and aKGDHC
in terms of TCA enzymes, what is inhibited by high levels of ATP
Isocitrate DH
in terms of TCA enzymes, what is activated by high levels of calcium
Isocitrate DH and aKGDH
Why is Ca++ important
signals muscle contraction and allows for production of ATP for fuel
what inhibits citrate synthase
high levels of ATP, NADH, and Succinyl-CoA
what inhibits isocitrate dehydrogenase
high level of ATP
what activates isocitrate DH
high levels of ADP, Ca++, and NAD+
what inhibits aKGDH
high levels of NADH and Succinyl-CoA
what activates aKGDH
High levels of AMP and Calcium
what activates citrate synthase
high levels of ADP
T/F another function of TCA cycle is to provide intermediates to fuel catabolic pathways
F, it is biosynthetic pathways (anabolism)
what other pathways can citrate feed off to?
Fatty Acids (B-oxidation)
Cholesterol
what pathway can a-ketoglutorate feed of to and what pathway can feed into it
Amino Acids
NT synthesis of Purines ( A and G )
what pathway can succinyl-CoA feed off to
Porphyrins (O2 transport)
what pathways feed into succinyl-CoA (Hint: list the specific Amino Acids)
Odd-chain FAs
Isoleucine , Methionine, and Valine
what specific amino acids feed into fumarate
aspartate
tyrosine
phenylalanine
what pathway can feed into Oxaloacetate
Amino Acid
what pathway can oxaloacetate feed off too
Amino Acids
TO MALATE for Filling up RXn
Malate can feed off to what pathway
Glucose
Draw a simple diagram for the anaplerotic Reactions
slide 25 on Regulation
what are the three enzymes that catalyze the anaplerotic reaction that replenish TCA cycle intermediates
PEP carboxylase
Pyruvate carboxylase
Malic Enzyme
PEP carboxylase function in anaplerotic rxns
converts PEP to oxaloacetate
Pyruvate carboxylase function in anaplerotic rxns
converts pyruvate to OAA
Malic Enzyme function in anaplerotic rxns
converts pyruvate into malate
What is the purpose of the anaplerotic reactions?
Replenish TCA cycle intermediates.
When we have high concentrations of pyruvate we want it to be converted to Acetyl-CoA so it can be consumed creating more e- carriers and allowing for energy to be synthesized!
what are the two routes in the malate aspartate shuttle
- Aspartate aminotransferase
- Malate DH
What does aspartate aminotransferase do in the matrix and in the cytosol?
converts OAA to aspartate in the matrix using an amino acid and releasing a-keto acid
in the cytosol aspartate is converted to OAA by a-keto acid reacting with aspartate releasing amino acid making OAA
how is aspartate aminotransferase different from malate DH
Does not require NAD/NADH
deals with moving nitrogen
how is malate DH different from aspartate aminotransferase
requires NAD/NADH
deals with moving e-
draw simple diagram for malate-aspartate shuttle
slide 30 on Regulation slide
draw simple diagram for glycerophosphate shuttle
slide 31 on regulation slides
when will the glycerophosphate shuttle be active
active when we need to make ATP as fast as possible ( doing physical activity)
what shuttle results in the loss of 1 ATP
Glycerophosphate
when will the malate aspartate shuttle be active
in a relaxed state
What are the three steps of Glycerophosphate shuttle
- ketones converted to alcohol
- OH converted back to ketone
- FADH2 trasports 2e- to ETC
Function of 3-Phosphoglycerol DH
Oxidizes NADH while converting DHAP (ketone) to 3-Phosphoglycerol (alcohol)
Function of flavoprotein DH ( has two functions)
- FAD reacts with 3PG , converting 3PG (alcohol) to DHAP (ketone), while being reduced FADH2
- Allows for FADH2 to do 2e- transfer to ETC
T/F FADH2 is part of flavoprotein DH that transports 2e- to ETC
T
Glyoxylate Cycle is done by ,
plants and some bacteria
how is Glyoxylate cycle different from TCA
CO2 releasing steps are bypassed and an extra acetate is utilized
what are the short-circuiting enzymes in the Glyoxylate cycle
Isocitrate lyase and malate synthase
what enzymes do isocitrate lyase and malate synthase replace from TCA
Isocitrate DH and a-KGDHC
what carbon source do plants rely the most on
acetate
Draw all the intermediates of the TCA cycle
look at TCA powerpoint slides
Draw ETC showing pumping of H+ , NADH, FADH2
look at ETC slides
How many protons = 1 ATP
4 H+
If 4H+ = 1 ATP, where do we get the 4 H+ from
1 H+ to transport ATP out
3 H+ from ATP synthesis via ATP synthase
How do we get 2.5 ATP per 1 NADH ?
10 H+ ( from ETC) / ( 4 H+/1 ATP) = 2.5 ATP
How do we get 1.5 ATP per 1 NADH?
6 H+ (from ETC) / ( 4 H+/1 ATP) = 1.5 ATP
what transports ATP out of the matrix to the IMM space ?
a translocase
why is the ATP movement favored out of the matrix
ATP movement is favorable out of the matrix because the IMM space is positively charged compared to the negatively charged matrix
what amino acid is responsible for picking up H+ from the IMM Space in ATP Synthase (include the specific subunit)
Aspartate subunit C
Describe how Aspartate is used in ATP synthase
- aspartate becomes protonated by picking up H+ ( becomes aspartic acid)
- causes a clockwise rotation
- As rotation continues it approaches subunit c where it can transfer a H+ to Ser
- H+ becomes released
How many ATP are created by a 360° rotation of gamma subunit of ATP synthase?
3 ATP
How many ATP are created by a 2 revolutions of gamma subunit of ATP synthase?
6 ATP
( 1 revolution = 3 120 ° rotations = 3 ATP , just multiply by 2)
Characteristics of F0 in ATP synthase
membrane bound
allows for the favorable movement of H+ to induce conformational changes in F1
Characteristics of F1
on the matrix side
3 aB active sites where ADP+P bind to create ATP
describe the order of the binding sites in the aB subunits of ATP synthase
L –> T —> O
L ( loose) binding site function
where ADP+ Pi bind
T ( tight ) binding site function
where the chemistry happens forming ATP
O ( nonbinding) site function
where ATP is release from going back to its original state
function of y-subunit
rotates 120° degree for aB subunits to have 3 distinct conformations
membrane potential equations in terms of protons
∆ G = RT∆PH + ZF(∆MP)
how many protons are pumped out of the matrix per NADH?
10 H+
how many protons are pumped out of the matrix per FADH2?
6 H+
Define repirasomes
they are multimeric supercomplexes
that function in a state where two or more complexes are associated
Why is it important for ETC to have supercomplexes like repirasomes
- greater efficiency for ATP production and respiration
- presence of certain complexes positively influence other complexes
how many electrons are transferred in a complete Q-cycle
4 e- are transferred sequentially , S.E.T
Why is it important for complex IV to transfer electrons in batches of 4
shields the rest of the cell from reactive intermediates
O2- , H2O2, OH- + OH are all examples of
reactive oxygen species (ROS)
which complex produces the least amount of ROS? How about the complex that produces the most?
Complex IV
Complex I
cytochrome c reduces what complex?
complex IV
what oxidizes complex IV
O2
what are the e- carriers in complex IV
cytochromes
copper
Function of complex IV
pumps 2 H+ across mitochondria inner membrane
Cytochrome C oxidase is in what complex
Complex IV
Cytochrome C characteristics
mobile e- carrier
water soluble
where can cytochrome C be found
associated on the inner mitochondrial membrane space
function of cytochrome c
shuttles electrons from complex III to complex IV
draw the first half of the Q cycle
slide 26 ETC presentation
draw the second half of the Q cycle
slide 27 ETC presentation
UQH2 —> Rieske Fe-S —> Cyt c.
occurs where?
first half of the Q cycle
what occurs in the first half of the Q cycle?
- QH2 travels across the inner mitochondrial membrane and donates 1 e- and 2 H+
- QH2 IS oxidized to Q●- and stays inside the membrane
- 1 e- then is transferred to bL heme –> bH heme
what occurs in the second half of Q cycle
- 2nd QH2 travels across the inner mitochondrial membrane and donates 1 e- to bH and 2 H+ are released
- QH2 oxidized to Q●- and reacts with the first Q●- to produce QH2 and Q
what are the different fates of QH2 and Q in the Q cycle?
Q will go back to Complex I or II to pick up e-
QH2 will travel across the inner mitochondrial membrane and start the cycle again
function of complex III
mediates electron transport from Coenzyme Q to Cytochrome c
Coenzyme Q - cytochrome c oxidoreductase is found in what complex
complex III
What reduces and oxidizes complex III
QH2 reduces
Cytochrome C is oxidizes
what are the e- carriers found in complex III
FeS
cytochromes
what is the principal transmembrane protein in complex III
b cytochrome with hemes bL and bH
CoQ passes electrons to ____ in a unique redox cycle known as the ____ ______
Cytochrome C
Q cycle
How many protons are pumped from Complex III
4 H+
Succinate-coenzyme Q oxidoreductase is found in
Complex II
T/F complex II utilizes Fe-S clusters and hemes to move e-s
T
How is Complex II different from the other three complexes
it does not pump protons across to the IMM space
what complex reduces FADH2 to Q forming QH2
Complex II
why does complex II take its e-s from FADH2 and not NADH
it takes less energy to reduce FADH2 than NADH
How many protons are released from complex I
4 H+
in what complex does this occur
NADH —> Complex I —-> QH2
Complex I
What complexes strips off e-s from NADH ?
Complex I
what are the e- carriers in complex I
FMN and Fe-S
Draw Q structure
slide 16 of ETC
Draw QH● structure
slide 16 ETC
Draw QH2 structure
slide 16 ETC
how is FADH2 similar to QH2
can both undergo single electron transfers (SET)
NADH- coenzyme Q oxidoreductase is found in
complex I
what reduces complex I and what oxidizes it
NADH reduces
CoQ is oxidizes
final electron acceptor of oxidative phosphorylation
O2
CoQ characteristics
lipid soluble e- carrier
moves within the lipid bilayer
what process is the following below:
NADH + H+ + 1/2O2 —-> NAD+ + H2O
Electron Transport Chain
In the presence of uncouplers energy is converted to
heat
what are other sources of entry into ETC
Acyl-CoA DH
Glycerol-P-oxidase
For ATP to be made what must be present in the matrix
ADP
Pi
H+
malate-aspartate shuttle is used in what organs
the liver, kidney, and heart
glycerophosphate shuttle is used more in what kind of organs
skeletal muscle and the brain
name the shuttle that couples cytosolic oxidation of NADH with mitochondrial reduction of FAD
Glycerophosphate shuttle
what is the net yield of ATP for 1 glucose molecule undergoing complete oxidation via gylcerophosphate shuttle?
30 ATP
what is the net yield of ATP for 1 glucose molecule undergoing complete oxidation via malate-aspartate shuttle
32 ATP
ROS are generated when
oxygen is only partially reduced
what ROS serves as the precursor for other types of ROS
superoxide radical (O2-)
what is the most potent oxygen radical
hydroxyl radical (OH-)
how do we form hydroxyl radical
Fenton chemistry using oxidation of Fe2+ with the splitting of hydrogen peroxide ( H2O2)
H2O2 + Fe2+ —> OH + OH- + Fe3+
what is this process called and what does it form
Fenton Chemistry
Forms hydroxyl radical
In terms of ROS what is the function of antioxidants
destroy oxidative free radicals
Superoxide Dismutase function
convert superoxide to hydrogen peroxide
hydrogen peroxide is targeted by two enzymes for conversion of water what are they?
catalase
Glutathione Peroxidase
what enzyme catalyzes this process
2O2- + 2H+ –> H2O2 + O2
superoxide dismutase
where can we find superoxide dismutase
in the mitochondrial containing Mn
cytosol containing Cu and Zn
what is known as the first line of defense against ROS
Superoxide Dismutase
where can we find Glutathione
mitochondria
where can we find GSH reductase
erythrocytes
function of GSH peroxidase
eliminate hydrogen peroxides
function of NADPH in terms of GSH
donates electrons to GSSG
regenerates GSH and NADP+
function of GSH reductase
regenerate GSH
eliminate H2O2
What enzyme involves the use of a heme where a radical cation is generated
catalase
what is known for being generated as part of normal metabolism of oxygen
endogenous ROS
what known for being generated from pollutants, tobacco,smoke, drugs, or radiation
exogenous ROS
why do we care about oxidative stress
it can lead to a number of degenerative diseases associated with oxidative damage to mitochondria
what TCA intermediate is known as the primer for FA, cholesterol syntehsis , and histone acetylation
citrate
breakdown of citrate in the cytosol produces what to metabolites? via what enzyme?
OAA and acetyl CoA
ATP-citrate lyase
function of citrate carrier
responsible for efflux of acetyl-CoA from mitochondria to cytosol in form of citrate
what are the three modes of inhibition
complex inhibitors
ATP synthase inhibitors
Uncouplers
why do we care about inhibitors of ETC
let us know what is happening in each complex in terms of mechanisms
what are the inhibitors of NADH-UQ ( Complex I)
Rotenone
Amytal
Demerol
how do rotenone, amytal, and demerol inhibit complex I?
prevent the reduction of CoQ by stopping oxidation of Fe-S clusters
no longer passes e- from complex I to CoQ
What are the inhibitors of cytochrome c Oxidase ?
Cyanide
Azide
Carbon monoxide
what does cyanide and azide both block
cytochrome a3 ( ferric form)
what does carbon monoxide block
cytochrome a3 ( ferrous form)
T/F all of the inhibitors of complex IV bined to the heme of Cyt a3
T
name the inhibitor for ATP synthase
oligomycin
function of oligomycin
blocks movement of protons through the F0
where does oligomycin bind to and what it makes contact with
surface of the C10 ring making contact with two neighboring molecules
How do uncouplers function
by obtaining protons in the IMM space and carry them to the matrix side allow for ATP synthase to be bypassed
Name the inhibitor that are agents that disrupt the tight coupling between e- transport and ATP synthase
uncouplers
give an example of an uncoupler
Dinitrophenol
Draw glycoxylate cycle
slide 33
