Tricarboxylic Acid Cycle Flashcards
Names of the Tricarboxylic Acid Cycle
TCA Cycle, Krebs Cycle, Citric acid cycle
TCA is the final pathway where the ___________ of __________, ________, and ________ converge and their carbon skeletons being converted to _____.
Catabolism, carbohydrates, amino acids, fatty acids, CO2
Catabolic Pathways of TCA
Breakdown of some amino acids provides certain TCA cycle intermediates
Anabolic Pathways of TCA
Some TCA cycle intermediates feed into biosynthetic pathways, such as the synthesis of certain amino acids
What two molecules provide most of the energy, due to the terminal oxidation of all biomolecules?
NADH & FADH2
What is the TCA cycle coupled with? Mainly referring to the oxidative phosphorylation of the reduced carriers (NADH and FADH2)
Production of ATP in the ETC
where is the TCA cycle located?
The mitochondrial matrix (close to the ETC)
Linear Metabolic Pathway
Starts with 1 metabolite and ends up with a different one (glycolysis)
Cycle
starts with a certain metabolite that undergoes multiple steps forming different intermediates…but in the end the same initial metabolite is regenerated.
No net loss, no net gain.
Aka why it’s a CYCLE
Reaction required prior to TCA
Oxidative phosphorylation of pyruvate
steps of Oxidative Phosphorylation of Pyruvate
- Transported into the mitochondria
- by a mitochondrial pyruvate carrier or limited simple diffusion - Converted into Acetyl CoA by Pyruvate dehydrogenase complex
- often called PDH - CO2 must be released and NADH must be produced
What transports Pyruvate into the mitochondria?
Mitochondrial Pyruvate carrier
Or
Limited simple diffusion
What enzyme converts Pyruvate into Acetyl CoA?
Pyruvate Dehydrogenase (complex) or PDH
PDH
Protein aggregate of 3 separate enzymes:
E1: P-carboxylase
E2: dihydrolipoyl transacetylase
E3: dihydrolipoyl dehydrogenase
Cofactors of PDH
Thiamine pyrophosphate, TPP Lipoma idle Coenzyme A (CoA) FAD NAD+
Regulation of PDH
phosphorylation DEACTIVATES PDH
Dephosphorylation ACTIVATED PDH
Subject to substrate activation
Subject to product inhibition
Is PDH a reversible step?
NOPE DEF IRREVERSIBLE
PDH can be activated by:
Pyruvate NAD+ ADP Ca2+ (muscle) CoA
PDH can be deactivated by:
Acetyl CoA
NADH
ATP
Steps of TCA Cycle
- Synthesis of citrate from Acetyl CoA and oxaloacetate
- Isomerization of citrate
- Oxidative decarboxylation of isocitrate
- Oxidative decarboxylation of alpha-ketoglutarate
- Cleavage of succinyl CoA
- Oxidation of succinate to fumarate
- Hydration of fumarate
- Oxidation of malate to oxaloacetate
Citrate is a precursor for _________ and an inhibitor for ________
fatty acid synthesis, PFK1
What is suicide inhibition?
When the Isomerization of Citrate is potently inhibited by fluoroacetate which results in citrate accumulation
What are the irreversible steps of TCA?
Citrate synthesis, Oxidative decarboxylation of isocitrate, and Oxidative decarboxylation of alpha-ketoglutarate
Steps 1, 3 and 4
What is the rate limiting step of TCA?
Oxidative decarboxylation of isocitrate