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PBL > Biochem 21 HY > Flashcards

Biochem 21 HY Flashcards

1
Q

in the electron transport chain what donates electrons? where is the chain located?

A

NADH and FADH2; inner mitochondrial membrane

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2
Q

doxorubicin is a highly effective anticancer agent. it binds cardiolipin in cell membranes and then does what

A

inhibits components of oxidative phosphorylation causing an increase in free radicals

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3
Q

each complex uses the energy from_____ to pump protons to the cytostolic side of the inner mitochondrial membrane. What does this create?

A

electron transfer e- donated to transport chain while H+ from NADH is pumped across to generate electrochemical gradient/proton motive force

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4
Q

Energy from teh reduction of O2 is used for phosphorylation of ADP to ATP by what enzyme

A

ATP synthase

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5
Q

FAD and FMN(flavin mononucleotide) are both synthesized from what vitamin

A

riboflavin

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6
Q

NADH passes electrons via the NADH dehydrogenase complex(I) to ____ which accepts 2 electrons from NADH and passes single electrons to ____. This then transfers electrons to and from ____. Binding sites for all of these are located on NADH dehydrogenase

A

FMN; Fe-S; CoQ

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7
Q

Succinate dehydrogenase (part of TCA cycle and complex II of the electron transport chain) passes electrons from FADH2 through Fe-S centers that enter the electron transport chain at what location

A

CoQ level

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8
Q

CoQ( has oxidize quinone) accepts an electron from Fe-S centers it first forms _____ a free radical(this is the major site for generation of toxic free radicals) it goes on to accept another electron to become?

A

semiquinone; reduced quinone(or ubiquinone)

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9
Q

cytochromes of the electron transport chain contain a bound___

A

heme- has Fe

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10
Q

what component of cytochromes is reduced when they accept an electron from CoQ?

A

the Fe in the heme group Fe3+–>Fe2+

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11
Q

cytochrome oxidase is the last complex that recieves electtrons from cytochrome C and transfers them to oxygen what is the composition of the complex and what metal does it contain

A

cytochrome A and a3(+oxygen bidning site) they contain Cu

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12
Q

the Cu contained in cytochromes a and a3 of the cytochrome oxidase complex collect how many electrons? when electron transfer happens to O2 what is produced?

A

4; 2 molecules of H2O

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13
Q

fatigue in iron deficient anemia is due impart from?

A

lack of electron transport (dt Fe def) for ATP production

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14
Q

the iron in heme in hemeglobin never changes its oxidation state because if it did its oxygen binding capacity would be lost what accounts for this difference in iron oxidation states between Hb and cytochromes

A

protein structures binding heme either protect it from oxidation or allow for oxidation

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15
Q

In HbM a rare Hb variant, a tyrosine is substituted for a histidine in normal HbA what does this tyrosine do

A

stabilies Fe3+ form of heme so they can’t bind oxygen-is lethal if homozygous

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16
Q

energy from oxidation-reduction reactions of the electron transport chain is used to transport protons from the matrix to the intermembrane space

A

chemiosmotic theory

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17
Q

what is the overal delta G of the electron transport chain(+/-) is it reversible

A

-; so negative that it is nerver reversible!

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18
Q

For each NADH oxidized how many ATP are formed? FADH2?

A

2.5;1.5

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19
Q

what portion of the electron transport chain is inhibitied by cyanide(a break down product of medication nitroprusside)

A

cytochrome aa3 component of cytochrome C oxidase complex

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20
Q

what is the effect of cyanide inhibition upon proton pumping and ATP synthesis

A

if it complete inhibition of one complex stops pumping at all complexes partial inhibition can occur and results in a partial decrease in rate of ATP synthesis

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21
Q

intravenous nitroprusside rapidly lowers elevated blood pressure but during prolonged infusions it gets converted to cyanide inhibitor of cytochrome c oxidase complex. small amounts of cyanide are detoxified in the liver to form? this can be monitored in the urine

A

thiocyanate

22
Q

mutations of OXPHOS disease occur in what 2 DNA

A

mitochondrial or nuclear

23
Q

why does an impairment of the electron transport chain cause lactic acidosis

A

NADH oxidation to NAD+ occurs in electron transport chain if NADH levels inc dt a defect in the chain then def NAD causes accumulation of pyruvate which is then converted to lactate causing lactic acidosis

24
Q

mtDNA encodes for various subunits of the electron transport chain. if there is a mutant mtDNA it is ually in a cell that does have normal mtDNA as well however mtDNA mutations become worse with age and become permanent frequently why

A

mtDNA doesn’t have normal repair mechanisms

25
Q

primary target for cyanide toxicity

A

CNS

26
Q

HCN is released from cyanoglycosides by beta glucosidase in plant or intestinal bacteria. when present in human what organ inactivates cyanide and what is it converted to

A

liver;thiocyanate! excreted in urine!

27
Q

a pt presented with mm jerking that worsened over 10 years causing hypoventilation, mild cardiomyopathy, and neurosensory hearing loss. it was found that all the women of her mothers family had symptoms involvng nervous or mm tissue also. what disease does the pt have and what is the defect

A

MERRF( myoclonic, epilepsy and ragged red fiber disease) caused by mutn in mtRNAl-lys

28
Q

mt DNA and nDNA mutations are often seen in nervous system, skeltal mm, heart, and kidney. why

A

all have high ATP requirements!! lost of mitochondria!!!

29
Q

the concentration of what control the rate of oxygen consumption of the ETC?

A

ADP

30
Q

ADP is phosphorylated to ATP by ATP synthase. This requires protons flowing through this complex into the matrix which decreases the proton gradient what happens in response

A

ETC pumps more protons and reduces O to H2O NADH is donating electrons and protons so more NAD+ is avail to go to TCA cycle

31
Q

what is uncoupling of oxidative phosphorylation

A

protons leak back into the matrix dissipating the electrochemical gradient so ATP isnt generated

32
Q

uncoupling of oxidative phosphorylation results in

A

increased oxygen consumption and heat production as electron flow and proton pumping attempt to maintain electrochemical gradient

33
Q

chemical uncouplers are known as proton ionophores and are lipid soluble what do they do

A

get into the inner mitochondrial membrane and grab protons from inner membrane space where there concentration is high and put them into the matrix dissipating electrochemical gradient; ATP syn stops!

34
Q

uncoupling proteins form channels in the innermembrane space and do what

A

dissipate gradient stop ATP synthesis

35
Q

how does shivering generate heat

A

inc ATP use which stimulates ETC inc O consumption and inc energy lost as heat

36
Q

brown adipose tissue has a lot of mitochondria and is found in human infants especially around their neck what is the uncoupling protein located ehre called and what does it cause

A

UCP1(thermogenin) causes non shivering thermogenesis

37
Q

in response to cold norepinephrine is released activating a lipase in brown adipose tissue causes FA release which stimulates UCP1 what then occurs

A

transport of protons from cystolic side to matric side with no ATP generation generating heat

38
Q

Ivy Sharers AIDs was being treated by zidovudine which is an inhibitor of mtDNA polymerase what is the side effect of this

A

mtDNA depletion in some cells causing ragged red fiber accumulation

39
Q

a person takes high doses of aspirin results in salicylate poisoning this causes partial uncoupling of mitochondria ETC inc AMP in the cell what can result

A

stimulation of glycolysis-pyruvate–>lactatic acid–>lactic acidosis

40
Q

inner mitochondrial membrane is pretty impermeable. what is used to exchange ADP for ATP? what drives this?transport Pi and pyruvate into the cell?

A

ATP-ADP translocase; driven by electrochem gradient!; Pi and pyruvate are transported with an H+ via a symport

41
Q

the outermitochondrial membrane is very permeable what is located in the membrane that allows for this

A

BDAC-voltage dependent anion channels-always open at low transmembrane potential

42
Q

this is located where inner/outermitochondrial membrane form a junction. is used in ATP/ADP exchange is opens if excess Ca ROS are present such as in hypoxia

A

mitochondrial permeability transition pore

43
Q

what occurs when the MPTP opens

A

protons flood into it ions enter the matrix mito swell and become damaged causes cell lysis and necrosis

44
Q

investigators report finding antibodies against cardiac ATP-ADP translocase in an individual who died of a viral cardiomyopathy how could the antibodies cause death

A

ATP gets used up forming ADP which must be exchanged by this translocase in the mitochondria to be converted to ATP if not results in rapid ATP depletion and death

45
Q

hyperthyroidism causes an the patient to feel hot and sweaty. what is activated in the mitochondria that can cause this

A

uncoupling proteins!

46
Q

isolated liver mitochondria are incubated in the presence of malate. after adding the substrate cyanide is added and the rxn proceeds for a few more minutes. which of the compnents of the ETC will be in an oxidized state

A

complex II-to be oxidized must have donated or never had electrons-complex 2 requires succinate which was never avail for the experiment

47
Q

liver mitochondria placed in a buffered solution. malate is added as energy source and an inc in oxygen consumption confirms that ETC is functioning. valinomycin and potassium are then added in the mitochondrial suspension. Valinomycin is a drug that allows K+ ions to move freely across the inner mitochondrial membrane. What is the effect on the proton motive force that had been generated by malate oxidation

A

proton motive force will be decreased but to a value greater than 0

48
Q

proton motive force/electrochemical gradient 2 components

A

pH, and electrical component

49
Q

dinitrophenol acts s an uncoupler of oxidative phosphorylation by what mechanism

A

allowing proton exchange across inner mitochondrial membrane

50
Q

woman presents with chronic fatiue. blood tests order suggest that her RBC is low dt iron def anemia. Why would this def lead to fatigue

A

her decrease in Fe-S centers is impairing the transfer of electrons in ETC

51
Q

what would you expect to see in a patient with an OXPHOS disease

A

high NADH:NAD+ ratio in mitochondria dt ETC deficiency bc of mtDNA encoding of components

PBL (19 decks)

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