Sessions 11 and 12 - Krebs Flashcards
what is the entry way to fully oxidizing glucose into CO2 and H2O
acetyl CoA which is formed from pyruvate inside mitochondria
what are the 2 main stages of the citric acid cycle
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.
where does oxidative decarboxylation of pyruvate and the citric acid cycle take place
within the matrix
what is released when pyruvate is made into acetyl CoA
CO2 and 2 e-
what is released from a single round of the krebs cycle
2 CO2 8 e- and 1 ATP
describe the inner membrane of mitochondria
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
what is a key irreversible step in metabolism of pyruvate to acetyl CoA
the synthesis of acetyl CoA by pyruvate dehydrogenase complex.
describe how animals regulate the pyruvate dehydrogenase complex
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
describe E1
pyruvate dehydrogenase component. 24 chains. its prosthetic group is TPP. it catalyzes the oxidative decarboxylation of pyruvate
describe E2
dihydrolipoyl transacetylase. 24 chains. its prosthetic group is Lipoamide. it catalyzes the transfer of acetyl group to CoA
describe E3
dihydrolipoyl dehydrogenase. 12 chains. its prosthetic group is FAD and it catalyzes the regeneration of the oxidized form of lipoamide
what is the rate limiting step of transformation of pyruvate to acetyl CoA
the first step decarboxylation by E1
describe the 2 mechanisms by which the pyruvate dehydrogenase complex is regulated
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
is PDH switched on or off when energy charge is high
it is switched off when energy charge is high
what happens to pyruvate in the liver if it is in the fed state
acetyl CoA is exported as citrate for fatty acid synthesis: pyruvate–> CO2 + acetyl CoA –> citric acid cycle
what happens to pyruvate in the liver if it is in the fasting state
acetyl CoA accumulates as a result of fatty acid oxidation: pyruvate + CO2 –> oxaloacetate –> gluconeogenesis
what happens in a phosphatase deficiency
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
describe a pathological increase in PDH kinase activity
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
how many NADH and FADH2 are released in a cycle of the the krebs cycle
3 NADH (6 electrons) and 1 FADH2 (2 electrons) so 8 electrons total
where do the 3 NADH molecules come from in krebs
two NAD+ are reduced in oxidative decarboxylations of isocitrate and a-ketoglutarate. and the third NAD+ is reduced in the oxidation of malate
where does FADH2 molecule come from in krebs
FAD is reduced in oxidation of succinate
where do the two molecules of CO2 come from in krebs
from the oxidative decarboxylations of isocitrate and a-ketoglutarate
where are the 2 H2O molecules consumed
one in synthesis of citrate by hydrolysis of citryl CoA and the other in the hydration of fumarate
what are the 2 main regulatory sites of the krebs cycle
isocitrate dehydrogenase and a-ketoglutarate dehydrogenase
what are the stimulators and inhibitors of isocitrate dehydrogenase
it is allosterically stimulated by ADP. while it is inhibited by ATP and NADH
what are the stimulators and inhibitors of a-ketoglutarate dehydrogenase
no stimulators and it is inhibited by ATP, succinyl CoA, and NADH
how does the krebs cycle function in transporting oxaloacetate into the cytoplasm to be used for gluconeogenesis
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
what happens in krebs cycle when the energy needs of the cell are met
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
