Sessions 11 and 12 - Krebs

Question 1

what is the entry way to fully oxidizing glucose into CO2 and H2O

Answer 1

acetyl CoA which is formed from pyruvate inside mitochondria

Question 2

what are the 2 main stages of the citric acid cycle

Answer 2

the first stage two carbon atoms are introduced into the cycle by coupling to oxaloacetate to form citrate, and two carbons are released as CO2 as citrate is metabolized to a four-carbon molecule. the 2nd stage of the cycle the resulting four carbon molecule is metabolized to regenerate oxaloacetate allowing for continued function of the cycle.

Question 3

where does oxidative decarboxylation of pyruvate and the citric acid cycle take place

Answer 3

within the matrix

Question 4

what is released when pyruvate is made into acetyl CoA

Answer 4

CO2 and 2 e-

Question 5

what is released from a single round of the krebs cycle

Answer 5

2 CO2 8 e- and 1 ATP

Question 6

describe the inner membrane of mitochondria

Answer 6

80%:20% protein to lipid which is very high compared to 50:50 in outer membrane. many proteins are needed as carriers. it is impermeable to NAD(H), NADP(H), CoA-SH or acyl CoA

Question 7

what is a key irreversible step in metabolism of pyruvate to acetyl CoA

Answer 7

the synthesis of acetyl CoA by pyruvate dehydrogenase complex.

Question 8

describe how animals regulate the pyruvate dehydrogenase complex

Answer 8

phosphorylation of the pyruvate dehydrogenase component E1 by pyruvate dehydrogenase (PDH) kinase switches off the activity of the complex. deactivation is reversed by the action of PDH phosphatase

Question 9

describe E1

Answer 9

pyruvate dehydrogenase component. 24 chains. its prosthetic group is TPP. it catalyzes the oxidative decarboxylation of pyruvate

Question 10

describe E2

Answer 10

dihydrolipoyl transacetylase. 24 chains. its prosthetic group is Lipoamide. it catalyzes the transfer of acetyl group to CoA

Question 11

describe E3

Answer 11

dihydrolipoyl dehydrogenase. 12 chains. its prosthetic group is FAD and it catalyzes the regeneration of the oxidized form of lipoamide

Question 12

what is the rate limiting step of transformation of pyruvate to acetyl CoA

Answer 12

the first step decarboxylation by E1

Question 13

describe the 2 mechanisms by which the pyruvate dehydrogenase complex is regulated

Answer 13

acetyl CoA and NADH inhibit the complex. the complex is also regulated by energy charge, ATP. ADP and pyruvate stimulate the complex. enzyme E1 is key site of regulation, the kinase phosphorylates it and inhibits it while a phosphatase removes the phosphate and thereby activates the enzyme

Question 14

is PDH switched on or off when energy charge is high

Answer 14

it is switched off when energy charge is high

Question 15

what happens to pyruvate in the liver if it is in the fed state

Answer 15

acetyl CoA is exported as citrate for fatty acid synthesis: pyruvate–> CO2 + acetyl CoA –> citric acid cycle

Question 16

what happens to pyruvate in the liver if it is in the fasting state

Answer 16

acetyl CoA accumulates as a result of fatty acid oxidation: pyruvate + CO2 –> oxaloacetate –> gluconeogenesis

Question 17

what happens in a phosphatase deficiency

Answer 17

enhance PDH kinase activity inhibits the pyruvate dehydrogenase complex. pyruvate is subsequently processed to lactate which can result in lactic acidosis. production of lactate in the presence of oxygen is a characteristic of cancer cells

Question 18

describe a pathological increase in PDH kinase activity

Answer 18

hypoxia inducible factor-1, the transcription factor that enhances aerobic glycolysis in cancer cells, also stimulates expression of PDH kinase. the subsequent inhibition of the dehydrogenase prevents the formation of acetyl CoA and directs pyruvate to the synthesis of lactic acid

Question 19

how many NADH and FADH2 are released in a cycle of the the krebs cycle

Answer 19

3 NADH (6 electrons) and 1 FADH2 (2 electrons) so 8 electrons total

Question 20

where do the 3 NADH molecules come from in krebs

Answer 20

two NAD+ are reduced in oxidative decarboxylations of isocitrate and a-ketoglutarate. and the third NAD+ is reduced in the oxidation of malate

Question 21

where does FADH2 molecule come from in krebs

Answer 21

FAD is reduced in oxidation of succinate

Question 22

where do the two molecules of CO2 come from in krebs

Answer 22

from the oxidative decarboxylations of isocitrate and a-ketoglutarate

Question 23

where are the 2 H2O molecules consumed

Answer 23

one in synthesis of citrate by hydrolysis of citryl CoA and the other in the hydration of fumarate

Question 24

what are the 2 main regulatory sites of the krebs cycle

Answer 24

isocitrate dehydrogenase and a-ketoglutarate dehydrogenase

Question 25

what are the stimulators and inhibitors of isocitrate dehydrogenase

Answer 25

it is allosterically stimulated by ADP. while it is inhibited by ATP and NADH

Question 26

what are the stimulators and inhibitors of a-ketoglutarate dehydrogenase

Answer 26

no stimulators and it is inhibited by ATP, succinyl CoA, and NADH

Question 27

how does the krebs cycle function in transporting oxaloacetate into the cytoplasm to be used for gluconeogenesis

Answer 27

oxaloacetate leaves the mitochondrion by a specific transport system in the form of malate (6 o clock of the krebs cycle) where it is reoxidized to oxaloacetate in the cytoplasm

Question 28

what happens in krebs cycle when the energy needs of the cell are met

Answer 28

multiple different intermediates are drawn off from the cycle for biosynthesis. intermediates are replenished by the formation of oxaloacetate from pyruvate (pyruvate carboxylase does this and is the same enzyme used in the pathway for gluconeogenesis). this must be done because animals lack the enzyme for converting acetyl CoA to oxaloacetate