TCA cycle and the Electron Transport Chain

Question 1

Regulatory enzymes in PDH complex

Answer 1

PDH kinase and PDH phosphatase

Question 2

The 5 Co-enzymes in the PDH complex

Answer 2

E1- TPP
E2- lipoic acid and CoA
E3- FAD and NAD+

Question 3

PDH complex is regulated by _______ modifications

Answer 3

Covalent

Question 4

PDH kinase and PDH phosphatase regulate PDH complex as follows:

Answer 4

Kinase phosphorylates and deactivates

Phosphatase dephosphorylates and activates

Question 5

PDH Kinase is allosterically activated by:

Answer 5

ATP, Acetyl CoA and NADH

Question 6

PDH Kinase is allosterically inhibited by:

Answer 6

Pyruvate

Question 7

PDH phosphatase activiator:

Answer 7

Ca2+

Question 8

Citrate synthase is inhibited by:

Answer 8

Citrate

Question 9

Acontinase is inhibited by:

Answer 9

Flouroacetate (rat poisoning)

Question 10

Isocitrate dehydrogenase is inhibited by

Answer 10

ATP, NADH

Question 11

Isocitrate dehydrogenase is activated by

Answer 11

ADP

Question 12

Rate limiting enzyme of TCA cycle

Answer 12

Isocitrate dehydrogenase

Question 13

Coenzymes required for alpha-ketoglutarate dehydrogenase complex

Answer 13

TPP, lipoic acid, FAD, NAD+ and CoA

Mnemonic: TLC For Nancy

Question 14

Alpha-ketoglutarate dehydrogenase complex is inactivated by

Answer 14

NADH, Succinyl CoA

Question 15

Alpha-ketoglutarate dehydrogenase complex is activated by

Answer 15

Ca2+

Question 16

Arsenite inhibits _____ and _____

Answer 16

lipoic acid and alpha-KG

Question 17

Arsenic poisoning clinical findings:

Answer 17

Rice watery stools, vommiting, prolonged QT, garlicy smelling breath

Question 18

B1 (thiamine) deficiency >

Answer 18

TPP deficiency > Wernicke-Korsakoff syndrome in alcoholics > wernicke encephalopathy > ataxia, confusion and opthalmopelgia

Question 19

B2 (riboflavin) deficiency >

Answer 19

FAD > Cheilosis > Inflammation of lips, scaling at corners of mouth, dermatitis, corneal vascularization

Question 20

B3 (niacin) deficiency >

Answer 20

NAD+ > Pellagra > Diarrhea, dermatitis, dementia

Question 21

B6 (benzoic acid) >

Answer 21

Coenzyme A > Fatigue, sleep disturbances, impaired coordination > alopecia > dermatitis > enteritis > adrenal insufficiency

Question 22

Overall regulation of the TCA cycle:

Inhibitors and activators

Answer 22

Inhibitors - ATP, NADH, Succinyl CoA, Citrate

Activators: ADP, AMP, Ca2+

Question 23

Energy yield of TCA cycle:

Answer 23

12 ATP per Acetyl CoA or 24 per glucose mol

Question 24

Citrate is a precursor for:

Answer 24

Fatty acid synthesis

Question 25

alpha-keyoglutarate is a precursor for:

Answer 25

AA synthesis

Question 26

Succinyl CoA is a precursor for:

Answer 26

Heme synthesis

Question 27

Malate is a precursor for:

Answer 27

Gluconeogenesis

Question 28

Oxaloacetate is a precursor for:

Answer 28

AA synthesis

Question 29

Anaplerotic reaction

Answer 29

Pathways that replenish the intermediates of the TCA cycle

Question 30

5 important anaplerotic reactions

Answer 30

Pyruvate carboxylase - produces Oxaloacetate from pyruvate Glutamate > alpha-ketoglutarate Leucine/isoleucine > Succinyl CoA Tyr/phe > Fumarate Aspartate > oxaloacetate

Question 31

Pyruvate carboxylase deficiency

Answer 31

Causes lactic acidosis, seizures, muscle weakness, ataxia

Question 32

Pyruvate carboxylase is activated by

Answer 32

Acetyl CoA

Question 33

Pyruvate carboxylase requires _____ as a cofactor

Answer 33

Biotin

Question 34

Formation of ATP through the build up of H+ gradient in mitochondrial intermembrane space

Answer 34

Chemiosmotic coupling

Question 35

``` Complex I Complex II ________ Complex III ________ Complex IV Complex V ```

Answer 35

``` I - NADH dehydrogenase II - Succinate dehydrogenase Co enzyme Q III - Cytochrome C reductase Cytochrome C IV - Cytochrome C oxidase V - ATP synthase ```

Question 36

NADH/NAD+ and FAD/FADH2 are prosthetic groups for which complexes in the ETC?

Answer 36

I and II

Question 37

Heme groups are prosthetic groups for which complexes in the ETC?

Answer 37

III and IV

Question 38

Iron sulfur complexes are prosthetic groups for which complexes in the ETC?

Answer 38

I, II, III

Question 39

Copper ions are prosthetic groups for which complexes in the ETC?

Answer 39

IV

Question 40

Complex I pumps how many H+?

Answer 40

4

Question 41

Complex II pumps how many H+?

Answer 41

none

Question 42

Complex III pumps how many H+?

Answer 42

4

Question 43

Q cycle

Answer 43

e- pass from CoQ to Cyt C reductase | cycle passes twice so 4H+ are pumped

Question 44

Cytochrome C is ______ peripheral protein and its binding to Complexes III and IV are electrostatic involving _____ residues

Answer 44

Mobile | Lysine

Question 45

Complex IV will pump how many H+?

Answer 45

2

Question 46

_____ contains Cu ions which are required for _____

Answer 46

Complex IV | O2 reduction to H2O

Question 47

Azide, cyanide and carbon monoxide bind to?

Answer 47

hene group in cyt C in complex IV

Question 48

One C ring rotation produces how many ATP at ATP synthase?

Answer 48

3 ATP

Question 49

Chemical/toxic inhibitors or complex I

Answer 49

Rotenone

Question 50

Chemical inhibitor of complex III

Answer 50

Antimycin

Question 51

Chemical inhibitor of complex IV

Answer 51

Hydrogen sulfide, cyanide and azide

Question 52

Carbon monoxide as an inhibitor

Answer 52

inhibits complex IV by binding to hemoglobin | It has a stronger affinity to Hg than O2

Question 53

Oligomycin

Answer 53

Binds to F0 in ATP synthase which inhibits H+ from entering

Question 54

Uncoupling proteins

Answer 54

Present in BAT which allow H+ to leak back into mitochondrial matrix which allows energy to be released as heat > non shivering thermogenesis BAT is crucial in infants and promotes tolerance for cold temperature

Question 55

Synthetic uncouplers

Answer 55

2,4-dinitrophenol (2,4-DNP) | Aspirin (high doses)

Question 56

Most genetic abnormalities involivng the ETC are a results of mutations in _____

Answer 56

Mitochondrial DNA | Which mutates at a faster rate than nuclear DNA

Question 57

LHON

Answer 57

Lebers Hereditary Optic Neuropathy Caused by a defect in NADH dehydrogenase Leads to degeneration of the optic nerve and blindness

Question 58

MELAS

Answer 58

mitochondrial Myopathy, Encephalopathy, lactic Acidosis and Stroke Caused by at least 10 different mutations in mitochondrial tRNA

Question 59

Leigh Syndrome

Answer 59

caused by mutations in mDNA and nuclear genes Mutations in complexes I and IV and PDH complex Damage is seen in the brain stem causing hypotonia, nystagmus and psychomotor regression, opthalmoplegia

Question 60

Products of TCA

Answer 60

2 CO2 3 NADH 1 FADH2 1 GTP

Question 61

B1 (TPP) deficiency affects

Answer 61

PDH Complex | alpha-ketoglutarate dehydrogenase complex

Question 62

TPP is a crucial coenzyme for the following enzymes:

Answer 62

Transketolase PDH complex alpha-ketoglutarate deyhdrogenase

Question 63

____ and _____ generate _____ as the first step in heme biosynthesis

Answer 63

Succinyl CoA and glycine | δ-ALA

Question 64

____ and ____ are competitive inhibitors on complex ____

Answer 64

CO and NO | IV

Question 65

____ are ____ noncompetitive inhibitors on complex ____

Answer 65

CN and H2S | IV

Question 66

Cyanide inhibits complex ____

Answer 66

IV, cytochrome oxidase

Question 67

Niacin is a precursor for _____

Answer 67

NADH