Chapter 13: Citric Acid Cycle and Oxidative Phosphorylation Flashcards by Monica Fatorma

What are other names for the citric acid cycle?

“TCA” cycle
tricarboxylic acid cycle
Krebs cycle

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What is the energy released from oxidation in the citric acid cycle saved as?

NADH, FADH2, and guanosine triphosphate (GTP)

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Is there hormonal control of the citric acid cycle?

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What is the only enzyme in the citric acid cycle that is not found in the matrix of the mitochondria?

succinate dehydrogenase

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What enzyme catalyzes the rxn: GTP +ADP ⟷ GDP+ATP?

diphosphate kinase

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What inhibitis isocitrate dehydrogenase?

NADH and ATP

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What is the major control enzyme of the TCA cycle?

isocitrate dehydrogenasse

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What is isocitrate dehydrogenase activated by?

ADP

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What enzyme acts as PDH in the citric acid cycle, in that it needs the same coenzymes and cofactors to effectively function?

α-ketoglutarate dehydrogenase

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What are the cofactors/coenzymes required for the proper utilization of α-ketoglutarate dehydrogenase?

thiamine
lipoic acid,
CoA,
FAD,
NAD

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Another name for Succinyl-CoA synthetase?

succinate thiokinase

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What is the substrate level phosphorylation step that succinyl CoA synthetase catalyzes?

GDP to GTP

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Where is succinate dehydrogenase found? What is another function for it?

On the inner mitochcondrial membrane where it also functions as complex II of the electron transport chain

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What is the function of citrate synthase in the citric acid cycle?

condenses the incoming acetyl group with oxaloacetate to form citrate

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Draw out all the reactions and steps in the citric acid cycle.

Refer to image for answer

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What is another function for citrate besides an intermediate in the citric acid cycle?

citrate may leave the mitochondria (citrate shuttle) to deliver acetyl-CoA into the cytoplasm for fatty acid synthesis

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What is another function of succinyl-CoA besides an intermediate of the citric acid cycle?

Succcinyl-CoA is a high-energy intermediate that can be used for heme synthesis and to activate ketone bodies in extrahepatic tissues

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What is another use for malate besides as an intermediate in the citric acid cycle?

malate can leave the mitochondria (malate shuttle) for gluconeogenesis

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When intermediates are drawn out of the citric acid cycle does it slow or speed up?

it slows

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What are the 2 reactions of the citric acid cycle?

NADH + O2 -> NAD + H2O ΔG = -56 kcal/mol
FADH2 + O2 -> FAD + H2O ΔG= -42 kcal/mol

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What shuttles transfer electrons into the mitochondria for delivery to the ETC if NADH is produced in the cytoplasm?

the malate or α-glycerol phosphate shuttle

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Once NADH has been oxidized, can the NAD be used again?

NAD can be used again by enzymes that require it

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Where is FADH2 produced? What enzymes produce it?

by succinate dehydrogenase in the citric acid cycle and by Fatty Acyl CoA dehydrogenase the α-glycerol phosphate shuttle also takes FADH2 to the ETC

Both enzymes located in the inner membrane and can reoxidize FADH2

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What is the function of O2 in the electron transport chain?

to accept electrons

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Draw out the steps in oxidative phosphorylation.

refer to the diagram

Which enzyme oxidized NADH in the electron transport chain?

NADH dehydrogenase (complex I) It oxidizes NADH to NAD and then delivers its electrons into. the chain

What is the order by which the electrons are carried in the ETC to major inner membrane components?

1. NADH dehydrogenase (complex I) accepts electrons from NADH 2. Coenzyme Q (a lipid) 3. Cytochrome b/c1 (an Fe/heme protein); complex III 4. Cytochrome c (an Fe/heme protein) 5. Cytochrome a/a3 (a Cu/ heme protein; cytochrome oxidase, complex IV transfers electrons to O2

Succinate dehydrogenase and the α -glycerol phosphate shuttle enzyme re-oxidize their FADH2 and pass electrons directly to what main protein/lipid carrier located in the in the electron transport chain?

directly to Coenzyme Q

What are the 3 major complexes of the ETC?

Complexes I, III, and IV (NADH dehydrogenase, cytochrome b/c1 and cytochrome a/a3)

The electricity generated by the ETC is used to run pumps (translocators), which drive protons from which part of the mitochondria to which part?

from the matrix space across the inner membrane the into the intermembrane space creating a small proton (or pH) gradient

ATP synthesis by oxidative phosphorylation uses the energy of the proton gradient and is carried out by what complex that spans the inner membrane of the mitochondria?

F0/F1 ATP synthase complex

As protons flow into the mitochondria through the F0 component their energy is used by the F1 component (ATP synthase) to do what?

phophorylate ADP using Pi

Lactic acidosis in a MI is responsible for what specific changes in the heart?

protein precipitation and coagulation necrosis

What are some major biochemical effects when there is effective inhibition of the ETC?

* decreased O2 consumption * increased intracellular NADH/ NAD and FADH2/FAD ratios * decreased ATP

What are important inhibitors of the ETC to remember?

cyanide and CO (carbon monoxide) antimycin (cytochrome b/c1), doxorubicin (CoQ), and oligomycin (F0/F1 ATP synthase)

Cyanide MOA?

deadly poison because it binds irreversibly to cytochrome a/a3 preventing electron transfer to O2, and producing many of the same changes seen in tissue hypoxia

What are major sources of cyanide?

* burning polyurethane (foam stuffing in furniture and mattresses) * Byproduct of nitroprusside (released slowly; thiosulfate can be used to destroy the cyanide)

What are some antidotes for cyanide poisoning? MOA?

nitrites it given rapidly; they convert hemoglobin to methemoglobin which binds cyanide in the blood before reaching the tissue. sodium thiosulfate O2 also given if possible

What is the MOA by which CO can interfere with effective ETC action?

binds to cytochrome a/a3 but less tightly than cyanide. It also binds to hemoglobin displacing O2

Symptoms of CO poisoning?

headache, nausea, tachycardia, and tachypnea Lips and cheeks turn cherry red Respiratory depression coma

How to treat CO poisoning?

Give O2

What are some sources of CO poisoning?

* propane heaters and gas grills * vehicle exhaust * tobacco smoke * house fires * methylate chloride-based paint strippers

What are uncouplers of the ETC? definition

chemicals that decrease the proton gradient

What are some biochemical effects of uncouplers of the ETC?

* decreased ATP synthesis * increased O2 consumption * increased oxidation of NADH

Because rate of the ETC increases, with no ATP synthesis what is energy released as?

heat

What are some important uncouplers of the ETC?

2,4 dinitrophenol (2,4-DNP) and aspirin (and other salicylates)

What is the natural uncoupling protein found in brown adipose tissue?

(UCP (uncoupling protein), formerly called thermogenin)

Function of thermogenin?

allows energy loss as heat to maintain a basal temperature around the kidneys, neck breastplate, and scapulae in newborns

What are the most sensitive and specific markers of AMI (acute myocardial infarction)?

Troponin I and troponin T

Aspirin in high doses used to treat RA can result in uncoupling of oxidative phosphorylation. This leads to what biochemical symptoms in the body?

* increased O2 consumption * depletion of hepatic glycogen * pyretic effect of toxic doses of salicylate * symptoms may vary depending on degree of salicylate intoxication from tinnitus to pronounced CNS and acid-base disturbance

What are the products of molecular O2 species that are partially reduced?

ROS reactive oxygen species

What is the result of ROS formation in the body?

they react rapidly with lipids to cause peroxidation with proteins, and with other substrates, resulting in denaturation and precipitation in tissues

What are some ROS species?

* superoxide (O2-) * Hydrogen peroxide (H2O2) * hydroxyl radical (OH)

The small quantities of ROS produced in the ETC production are destroyed by what enzymes?

catalase and superoxide dismutase

What are conditions in which the rate of ROS can increase dramatically?

in conditions such as reperfusion injury in a tissue that has been temporarily deprived of O2

Describe ATP and NADH levels in tissue that has been temporarily deprived of O2?

ATP levels will be low and NADH levels high

How is reperfusion injury to tissue caused?

There is deprivation initially to the tissue so when O2 is suddenly introduced, there is a burst of activity in the ETC, generating incompletely reduced ROS

In the case of erythrocytes how are large amounts of superoxide generated?

by spontaneous dissociation of O2 from hemoglobin; products are methemoglobin and superoxide

Low levels of what in glucose 6 phosphate dehydrogenase deficiency result in accumulation of the destructive hydrogen peroxide?

NADPH

Does excess NADH inhibit or stimulate the citric acid cycle?

inhibits citric acid cycle