Dr. Agbas Lecture on Mitochondria

Question 1

Superoxide dismutase does what?

Answer 1

converts superoxide anion into hydrogen peroxide

Question 2

Glutathionine peroxidase catalase does what

Answer 2

converts free radial hydroxyls into water

Question 3

ONOO

Answer 3

peroxynitrite free radical nitrogen species

Question 4

nitrogen oxidation of what gives you free radical nitrogens?

Answer 4

arginine

Question 5

Ferrooxins (orange correlation box)

Answer 5

small proteins that carry electrons in mitrochondrial P-450 systems

contain iron and sulfur clusters that undergo redox rxns. importantly, Fe3+ –> Fe2+ allows it to be oxidant and reductant

Question 6

Adrenodoxin

Answer 6

an Fe-2/S2 ferredoxin FDX1

participates in biosynthesis of steroidal hormones

heme synthesis for cytochome c oxidase

metabolism of vitamin D

also involved in plant photosynthesis and metabolism

Question 7

mito matrix

Answer 7

site of beta oxidation of fatty acids, TCA cycle, urea cycle , ketone body synthesis , Ca2+ resevoir

Question 8

mito inner membrane

Answer 8

permeable only to CO2, O2, and NH3

Question 9

mito outer membrane

Answer 9

permeable to small ions as a result of protein channels called “porins”

Question 10

cytochrome C apoptosis

Answer 10

ctyo-c: mobile carrier between complexes III and IV

apoptotic events lead to formation of “mito permeability transition pore complex” which

activators of caspases when released into matrix

Question 11

Ubiquinone radical

Answer 11

the intermediate form of Co-Q (Co-Q -1, partially reduced) during transfer of electrons from Complex I to Co-Q, as well as in the transfer from reduced……..Q- can pass electron to O2 to form O2 - (superoxide)

Question 12

Which complex in the respiratory chain isn’t effected by a mutation in mito DNA?

Answer 12

complex II: it does not encode/contribute any protein to this complex

Question 13

defects in mito DNA which effect respiratory proteins are associated with what diseases?

Answer 13

midgut carcinoid tumors and other cancers due to increased production of ROS by defective mito

Question 14

Rotenone

Answer 14

naturally occurring pesticide
used as a natural fish poison for centuries
sunlight destroys it, preventing it from contaminating ground water
moderately toxic to people
inhibits NADH dehydrogenase complex I
Vitamin K3 overcomes inhibition
linked to parkinson disease in cases of chronic exposure

Question 15

cyanide poisoning

Answer 15

prevents O2 reduction by preventing electron transfer to O2 in terminal step by complex IV

byinds to Fe3+ or reduced form of iron in heme group of complex IV

can be reversed by nitrites: can convert Fe2+ to Fe3+ in hemoglobin causing creation of methemoglobin, which competes for binding in complex IV

THIOSULFATE can cause enzymatic conversion of CN to thiocyanate, which is nontoxic

Question 16

CN versus CO

Answer 16

CO and NO compete with O2 for binding to the reduced heme group (Fe2+) in complex four.

CN and N3- and H2S bind to oxidized form of heme Fe3+

Question 17

in what oxidation state does CN bind to the heme group iron?

in what oxidation state does CO bind to the heme group in iron?

Answer 17

Fe3+ — CN
Fe2+ —-CO

heme group in complex IV

Question 18

Aspirin overdose

Answer 18

doses above 150 mg/kg causes hyperthermia

salicylate uncouples oxidative phosphorylation by disrupting protein gradient across inner mitochondrial membrane. causes dissipation of energy as heat.

stimulates respiratory center in the brain and causes hyperventilation

treatment: hemodialysis and gastric lavage

Question 19

daily ATP production

Answer 19

free energy from adding Pi to ADP is 7.3 kcal/mol

Question 20

conversion of food energy into ATP is _____ % efficient

Answer 20

40%

Question 21

Cytochrome P-450

Answer 21

superfamily of enzymes another example of an electron transfer system that is of high biological relevance

Question 22

CYP

Answer 22

superfamily of enzymes another example of an electron transfer system that is of high biological relevance

Cytochrome P-450 superfamily

highly active in metabolism of hydrophobic compounds such as steroid hormones, eicosanoids, vitamin D, drugs, toxins etc.

they are “hemoproteins”

Question 23

how do CYPs work?

Answer 23

essentially, they transfer electrons from NADPH to O2: they transfer one electron to one atom of O which is subsequently incorporated into a protein substrate (R-OH) and another atom to the other atom of O which is reduced to water (H2O)

they catalyze this rxn

NADPH + O2 + R + H —> NADP + ROH + H20

Question 24

CYPs are ….

Answer 24

“mono-oxidases” and “hemeproteins”

Question 25

Hypoxia and ATP preservation

Answer 25

lowered O2 —> lowered Res chain activity –> lactate acidosis —> lowered pH in mito —> activation of inhibitory protein IF —> IF binds ATP synthase and prevents from acting in the reverse to hydrolyze ATP

Question 26

Malate-aspartate shuttle

Answer 26

in heart, liver, and kidneys

because NADH can’t cross mito membrane by itself

Question 27

steps of the malate-aspartate shuttle

Answer 27

NADH is oxidized in the cytoplasm by transferring two electrons to Malate dehydrogenate (c-MD)

cMD —> crosses mito outer membrane –> as transported across inner membrane while alpha-ketogluterate transported into inner membrane space —> malate oxidized by oxaloacetate, regenerating NADH in the process

oxaloacetate is reduced by glutamate into alpha-ketogluterate and is transferred out as another malate is transferred int. cycle continues