The TCA cycle Flashcards
What is the primary function of the TCA cycle
To convert energy available from the oxidization of Acetyl-CoA into 3 molecules of NADH, 1 FADH2 and 1 GTP during each turn
**produces 24 ATP
What is the first thing to *enter the TCA?
Citric acid
Where is the location of where the TCA takes place?
All cells with mitochondria
What causes regulation of the TCA?
Supply and demand of TCA cycle Availability of NAD and FAD as substrates Inhibition by NADH High-energy signals turn off Low-energy signals turn on
What is the role of oxaloacetate in the citric acid cycle?
Its 4 carbon and its what accepts 2 carbons from acetyl-CoA to create citrate which is 6 carbon (first product of TCA)
What is created per acetyl-CoA molecule?
You get 3 NADH (9 ATP), 1 FADH2 (2 ATP) and 1 GTP. Since glycolysis produces 2 acetyl-CoA you get double of those.
Total energy yield = 24 per TCA turn
what is the total energy produced from glycolysis and the TCA
38
Glyolysis = 8
Pyruvate to Acetly-CoA = 2 NADH = 6 ATP
TCA = 24
What does pyruvate dehydrogenase (PDH) do?
It links glycolysis to the TCA cycle. it catalyzes the production of acetyl-CoA which can then ever the TCA as fuel
**the bridge between glycolysis and the TCA
Why cant fatty acids contribute to gluconeogenesis?
All fatty acids are broken down to acetyl-CoA inside the mitochondria and we can not turn them into pyruvate, which means they are stuck in the mitochondria and can never be used to start the TCA
What is an important regulation site for the TCA cycle?
PDH this is because it regulates the flow of pyruvate into the TCA cycle
**pyruvate dehydrogenase is an important site for regulating energy metabolism
What is coenzyme A?
Its an acyl carrier biomolecule, which carries acetyl (2 carbons) or fatty acyl group during TCA cycle and fatty acid synthesis
How is CoA synthesized?
Its made from pantothenic acid (vitamin B5), cysteine (amino acid) and ATP
What is the main role of CoA?
It transfers fatty acids from the cytoplasm to the mitochondria and when it carries an acetyl group (2 carbon) its known as acetyl-CoA (used for adding 2 carbons and starting TCA)
What is pyruvate dehydrogenase and where does it work?
Its found in the mitochondrial matrix which catalyzes the rxn of pyruvate transfering two carbons to CoA to produce acetyl-CoA. It also produces NADH and CO2
How many subunits does PDH have ?
It a big complex and has three subunits E1, E2 and E3
It also has a number of cofactors, prosthetic groups and substrates
What is TPP?
Its thiamine pyrophosphate
Its a prosthetic group derived from thiamine (B1) which is bound to the E1 subunit of PDH
What is lipoic acid/lipoate/lipoaminde?
Prosthetic group that is covalently bound to PDH subunit E2
What is coenzyme A?
Derived from vitamin B5, its transiently bound substrate that is linked to the acetyl group of pyruvate. its a coenzyme
What is FAD?
Falvin adenine dinucleotide
Derived from vit B2
Its a prosthetic group permanently bound to subunit E3
What is NAD?
Nicotinaminde adenine diucleotide
Derived from nicotinic acid (B3)
Transiently bound cofactor
How many cofactors are needed in otder to a-ketoglutarate dehydrogenase catalyzed rxn in the TCA cycle?
You need all 5 cofactors
What stimulates and inhibits PDH kinase?
High energy state (high NADH, FADH2, ATP) and accumulation of acetyl CoA
Pyruvate (end product of glycolysis) accumulation inhibits PDH
What is a thiamine deficiency?
Presentation is beriberi
Lower amounts of thiamine lead to lower thiamine pyrophosphate (TPP) and impaired activity of pyruvate dehydrogenase (PDH) as well as a-ketoglutarte dehydrogenase (of TCA cycle) and transketolase
**very dmging to the heart and brain which have large energy requirements
Where is acetyl-CoA mainly present?
In the mitochondria and can not come out to cytoplasm freely
What are the three irreversible steps of the TCA cycle?
Citrate synthase
Isocitrate dehydrogenase
a-ketoglutarate dehydrognease
***All blocked in high energy state
How is citrate synthase regulated in the TCA?
Inhibitors: ATP, NADH, citrate (product inhibition) and succinyl-CoA (mimics acetyl-CoA, a competitive inhibition)
What activates and inhibits Isocitrate Dehydrogenase?
Inhibitors: ATP, NADH
Activators: ADP
What inhibits a-ketoglutarate dehydrogenase?
Inhibitors: ATP/GTP, NADH, succinyl-CoA (product inhibition) and arsenic
**uses the same co-factors of pyruvate dehydrogenase
What are anaplerotic reactions?
These rxns add to the pool of TCA cycle intermediates at multiple points in the cycle from various dietary precursors
What are anabolic reactions?
Use the TCA cycle intermediates to make other important biomolecules
