metabolic regulation

Question 1

How is the ETC/ATP synthase regulated? including consequences of inhibition

Answer 1

negative: ATP
pos: ADP + Pi
consequences of inhibition: accumulation of NADH

Question 2

how is alpha-ketoglutarate DH regulated? including consequences of inhibition

Answer 2

neg: NADH
pos: none
consequences of inhibition: lower oxaloacetate

Question 3

how is isocitrate DH regulated? including consequences of inhibition

Answer 3

neg: NADH, ATP
pos: ADP
consequences of inhibition: accumulation of citrate

Question 4

how is citrate synthase regulated? including consequences of inhibition

Answer 4

neg: NADH and citrate
pos: acetyl coa and oxaloacetate
consequences of inhibition: accumulation of acetyl coa

Question 5

how is pyruvate dh regulated?

Answer 5

neg: NADH, acetyl coa
pos: ADP, pyruvate

Question 6

how is pyruvate kinase regulated?

Answer 6

neg: ATP, NADH, acetyl coa
pos: F-1,6-BP

Question 7

how is PFK regulated? including consequences of inhibition

Answer 7

neg: ATP, citrate
pos: AMP
consequences of inhibition: lower F-1,6-BP and accumulation of G-6-P

Question 8

how is hexokinase regulated?

Answer 8

neg: G-6-P

Question 9

which steps in glycolysis are regulated?

Answer 9

hexokinase, PFK, PK

Question 10

which steps in TCA cycle are regulated?

Answer 10

citrate synthase, isocitrate DH, alpha-KGDH

Question 11

Which enzymes does ATP inhibit?

Answer 11

PFK, OK, Citrate synthase, IDH, a-KGDH

Question 12

Which enzymes for NADH inhibit?

Answer 12

PK, PDH, citrate synthase, IDH, a-KGDH

Question 13

Which enzymes do ADP/AMP activate?

Answer 13

PFK, PDH, IDH, citrate synthase, a-KGDH

Question 14

which enzyme does ADP inhibit?

Answer 14

PDH-K

Question 15

How is the ETC regulated?

Answer 15

(+) ADP + Pi

(-) ATP

Question 16

What does G-6-P inhibit?

Answer 16

hexokinase

Question 17

What does citrate inhibit?

Answer 17

PFK and citrate synthase

Question 18

what does acetyl-coa inhibit?

Answer 18

PK, PDH

Question 19

what does succinyl coa inhibit?

Answer 19

a-KGDH and citrate synthase

Question 20

which part of the TCA cycle is regulated mainly by substrate availability?

Answer 20

citrate synthase from acetyl-coa and oxaloacetate

Question 21

How is PDH regulated?

Answer 21

inhibited by PDH kinase (which is activated by NADH and acetyl coa)
activated by PDH phosphatase (which is activated by insulin)

Question 22

What are the two ways that electrons from NADH in the cytosol can enter the electron transport chain?

Answer 22

Malate aspartate shuttle and glycerophosphate shuttle

Question 23

What are the benefits of the malate aspartate shuttle?

Answer 23

more efficient, because NADH is converted back to NADH, so no ATP is lost

Question 24

What are the benefits of the glycerophosphate shuttle?

Answer 24

Faster because e- are passed directly to an FAD in the inner membrane and the ETC but less efficient because NADH –> FAD means you get less ATP from it

Question 25

How does Pi from the cytosol enter the mitochondria?

Answer 25

through an H+/Pi symporter

Question 26

How does the H+/Pi symporter affect ATP synthase?

Answer 26

the H+ go with the pH gradient, thus reducing the H+ gradient used to drive ATP synthase, thereby reducing the energy available for ATP synthesis

Question 27

How does the Q cycle contribute to the generation of a proton gradient?

Answer 27

Oxidation of CoQH2 on IMS side releases protons to IMS. CoQ is always reduced on matrix side, so it releases protons from matrix to the IMS.

Question 28

Why does Q cycle contribute more to proton gradient than direct oxidation?

Answer 28

Undergoes multiple oxidations and one then gets rereduced so it leads to two more protons pumped

Question 29

How does a proton wire work

Answer 29

conformational changes due to e- transfer cause a series of nonconsecutive protonations and deprotonations of amino acid side chains which result in the net transfer of a proton from the matrix to the IMS

Question 30

What makes FMN and CoQ special electron carriers/acceptors

Answer 30

can accept or transfer 1 or 2 e- at a time | use a transient free radical intermediate (semiquinone)

Question 31

How many e- can NAD+ carry

Answer 31

obligated to carry 2e-

Question 32

how many e- can cytochromes carry/transfer

Answer 32

usually 1

Question 33

describe structure, location, and mechanism of electron transfer for CoQ

Answer 33

organic, lipid soluble molecule located in the mitochondrial inner membrane transfers 2 e- from C1 or 2 to C3 and carries 2H+ from matrix to IMS

Question 34

describe structure, location, and mechanism of electron transfer for cytochrome C

Answer 34

water soluble protein with a heme prosthetic group found in IMS carries 1 e- from C3 to C4

Question 35

What allows cytochromes to have different reduction potentials

Answer 35

the different microenvironments of the heme groups and the varying microenvironments of the proteins themselves

Question 36

what is an advantage of the Q cycle in C3

Answer 36

allows for 4H+ to be pumped into IMS instead of 2 from direct oxidation

Question 37

how are protons pumped in each complex of ETC

Answer 37

1: proton wire 2: not 3: Q cycle 4: proton wire

Question 38

What is the chemiosmotic hypothesis?

Answer 38

during the ETC, protons are transferred from the mito matrix to the IMS, generating a proton gradient. The dissipation of this drives ATP synthesis

Question 39

experimental observations which support chemiosmotic theory

Answer 39

a. Can measure the pH gradient across the mitochondrial inner membrane (membrane is impermeable to ions) b. Artificial pH gradient results in ATP synthesis c. Electron transport acidifies the cytosol d. ATP synthesis requires intact mitochondria e. Agents which destroy the pH gradient (uncouplers) prevent ATP synthesis

Question 40

where is Fo subunit located and what does it do

Answer 40

transmembrane unit which converts flow of protons into mechanical movement

Question 41

How is mechanical movement from Fo converted to ATP

Answer 41

communicated down the stalk portion to F1 unit which triggers conformational changes to drive ATP synthesis

Question 42

Where is F1 subunit located and what does it do

Answer 42

soluble unit in mitochondrial matrix and faciliatates conformational changes to drive ATP synthesis