TCA Cycle Flashcards
The TCA cycle _____ two carbons of acetate from acetyl CoA and generates NADH and FAD2H. In anabolism, it generates key intermediates for _____, _____, and _____
Oxidizes
Gluconeogenesis
Fatty acid synthesis
Amino acid synthesis
The TCA cycle occurs in the ___ of the mitochondria. The outer membrane is permeable to most molecules. The inner membrane is very ____. This allows a proton concentration gradient to be established across the ____ ___ of the mitochondria
Matrix
Impermeable
Inner membrane
The matrix naturally has ___ proton concentration. The inter-membrane space has naturally ____ proton concentration
Low
High
The electron transport chain requires genes and proteins from both ____ and ____ DNA
Nucleus
Mitochondrial
Mitochondrial DNA is more similar to _____ DNA then nucleus DNA
Prokaryotic
Mitochondrial DNA is _____ because it is naked, and not bound to histones in a chromatin structure. It is exposed to hire concentrations of ____ ____ ____. The mitochondrial DNA polymerase has limited ability to repair DNA damage.
Hypermutatable
Reactive oxygen species
Mitochondrial DNA is dynamic. There are multiple ____ of the mitochondrial DNA to help push back from the hypermutability, especially in energetics cells like ___ cells
Copies
Muscle
Many symptoms of mitochondrial disease are ____ due to energy starvation during fetal development
Neurological
Glycolysis occurs in the ____. Pyruvate, dehydrogenase, and the TCA cycle occur in the _____.
Cytosol
Mitochondria
Pyruvate is transported to the mitochondria via the _____ ____ ____ which acts as a heterodimer of two subunits: ____ and ____
MPC is located on the ____ ____ of the mitochondria.
Mitochondrial pyruvate carrier (MPC)
MPC1 and MPC2
Inner membrane
Inherited mutations in the mitochondrial pyruvate carrier causes ____ _____
Lactic acidosis
____ ____ is the link between glycolysis and the TCA cycle. It has four subunits. E1 subunit is ____ ____, with a thiamine pyrophosphate. E2 is a _____ with Lipoate and CoA. E3 is a ____ with FAD and NAD+. Keto acid dehydrogenase and branch chain ketoacid dehydrogenase share a similar organization.
Pyruvate dehydrogenase
Pyruvate decarboxylase
Transacetylase
Dihydrolipoyl dehydrogenase
Pyruvate dehydrogenase is regulated by reversible _____. When activated the ___ ___ will proceed. When inhibited, pyruvate will be converted into ____.
Phosphorylation
TCA cycle
Lactate
Pyruvate dehydrogenase is regulated by phosphorylation and dephosphorylation of ____ residues in ____ alpha subunits
Serine
E1
Pyruvate is converted into ____ by pyruvate dehydrogenase which then bonds to coenzyme A, forming ____
Acetate
Acetyl CoA
All reactions of the TCA cycle take place in the ____ ____
Mitochondrial matrix
Overview of TCA cycle:
____ ____ is the key rate limiting enzyme in the TCA cycle
Isocitrate dehydrogenase
The reaction from acetyl-CoA to citrate is energy yielding however, the following reaction is not energetically favorable. This allows for ____ to build up and be used as an intermediate for other biosynthetic reactions. This is like wise for ____.
Citrate
Malate
First step:
The enzyme ____ ____ hydrolyzes, the Theoester bond of acetyl CoA to join acetate and oxaloacetate, forming ____. Citrate has three carboxylic acid groups, making it a tricarboxylic acid.
Citrate synthesis
Citrate
Second step:
The enzyme ____ catalyzes a two step isomerization to convert citrate to _____, which is a tricarboxylic acid
Aconitase
Isocitrate
Third step:
____ ____ catalyzes this oxidative decarboxylate, isocitrate is converted into ____. It uses NAD+ and creates____. IDH1 in the cytosol and IDH2 in the mitochondria catalyze the same reaction but use ____ instead
Isocitrate dehydrogenase (IDH3)
Alpha-ketoglutarate
NADH
NADP+
Isocitrate dehydrogenase removes an ____ group from 6 carbon Isocitrate forming the 5 carbon alphaketoglutarate. _____ is a byproduct
Carboxyl
CO2
Fourth step:
_______ _____ catalyzes the final oxidative decarboxylation, forming _______ from alpha ketoglutarate. ____ and ____ are byproducts
This product is then added to acetyl CoA similar to pyruvate dehydrogenase enzyme.
Alpha-ketoglutarate dehydrogenase
succinyl CoA
NADH
CO2
Alpha ketoglutarate dehydrogenase removes a carboxyl group from the ____ carbon alpha-ketoglutarate forming the ___ carbon succinyl CoA.
At this point ___ carbons have been released as carbon dioxide, but not the same carbons that entered as acetyl CoA
5
4
2
Review:
Look at cofactors
Fifth step:
_____ ____ cleaves the Theoester bond, linking succinate and CoA this is a strongly extra Gondek reaction and the enzyme uses the energy to catalyze substrate level phosphorylation of GDP to make GTP. The end product is ____.
Succinate thiokinase
Sixth step:
____ _____ oxidizes succinate to introduce a double carbon-carbon bond forming ____. FAD is reduced to ___. Succinate dehydrogenase is a component of the electron transport chain transferring electrons from FAD2H to _____.
Succinate dehydrogenase
Fumarate
FAD2H
Coenzyme Q
Seventh step:
_____ _____ it’s a proton and hydroxyl from water to fumarate double bond forming ____.
Fumarate hydratase
Malate
Eighth step:
____ ____ oxidizes malate’s hydroxyl to a keto group forming _____ and reducing NAD+ to NADH in the process
Malate dehydrogenase
Oxaloacetate