Tricarboxylic Acid Cycle & Pyruvate Dehydrogenase (TCA Cycle) Chip 9 Flashcards
What does TCA Cycle stand for
Tricarboxylic Acid Cycle-also called the Citric Acid Cycle
What is TCA Cycle
Plays several roles in the metabolism
It is the final pathway where the oxidative catabolism of Carbohydrates
Amino Acids
Fatty Acids converge.
What happens to Carb/AA/Fatty acids as they converge
Their carbon skeletons is being converted to CO2
T/F Oxidation in the TCA Cycle provides energy for the production of the majority of ATP in most animals
True
Where does the TCA Cycle take place
Mitochondria
Electron transport reactions taking place in Mitochondria
Oxidize the reduced coenzymes (NADH & FADH2) produced by the cycle
TCA is considered Aerobic or Anaerobic pathway & why
Aerobic Pathway
BC= O2 is required as the final electron acceptor
What are the 8 intermediates involved in the TCA cycle
- Oxalacetate
- Citrate
- Isocitrate
- Alpha-Ketoglutamate
- Succinyl-CoA
- Succinate
- Fumarate
- Malate
What are the 8 Enzymes involved in the TCA cycle
- Citrate synthase
- Aconitase
- Isocitrate Dehydrogenase (IDM)
- Alpha Ketaglutarate Dehydrogenase
- Succinate Thiokinase
- Succinate Dehydrogenase
- Fumarase
- Malate Dehydrogenase (DMH)
Intermediates Mneumonics
Our City Is Kept Safe & Secure From Mobsters
Which pathway leads to Pyruvate formation ?
Glycolysis of Glucose a 6 Carbon compound splitting in to 2 molecules of Pyruvate
How many carbon compounds are there in Pyruvate
3 Carbon Compounds
In Step 1:
Pyruvate is converted to what intermediate
Acetyl-CoA
In step 1:
What is the process of Pyruvate and First intermediate formation?
Name the 1th intermediate being formed
Acetyl-CoA
Oxidation of Pyruvate into Acetyl-CoA
What Enzyme is responsible for Oxidation of Pyruvate into Acetyl CoA?
Enzyme Pyruvate Dehydrogenase Complex
How many Carbons in Acetyl-CoA
2 Carbon Compound
In Step 1 Reacton what is being generated
Molecule of CO2 & NADH is generated
In Step 2: Acetyl CoA combines with what Intermediate
Oxaloacetate (4 Carbon Molecule)
What intermediate is formed once Acetyl CoA combines with Oxaloacetate
Citrate (6 Carbon Molecule)
Combining of Acetyl CoA & Oxaloacetate to form Citrate is catalyzed by what Enzyme
Citrate Synthase
Citrate is isomarized into what intermediate
Isocitrate
What Enzyme isomarizes Citrate into Isocitrate
Aconitase
Isocitrate is then oxidized into what?
Alph-Ketoglutamate (5 carbon compound)
What Enzyme is used to irreversibly oxidize decarboxylation of Isocitrate into Alpha-Ketoglutamate
Isocitrate Dehydrogenase
Rate limiting step
Enzyme is allosterically activated by ADP (low energy signal) & CO2 inhibited by ATP & NADH
In the reaction between Isocitrate and Alpha- Ketoglutamate..what products are being reduced and generated
In this reaction:
A molecule of NAD+ is reduced into NADH & a molecule of CO2 is generated
What is Apha-Ketoglutamate converted into
Succinyl-CoA (4 Carbon Compound)
What enzyme is used to convert Apha-Ketoglutamate into Succinyl-CoA
Alpha-Ketoglutarate Dehydrogenase
In the reaction between Alpha-Ketoglutamate & Succinyl-CoA…what product is being lost or gained
1 Molecule of Carbon in lost into CO2
Molecule of NAD+ is reduced to NADH & molecule of CO2 is released
Succinyl-CoA is converted into what ?
Succinate
What Enzyme is used to convert Succinyl-CoA to Succinate?
Succinil CoA Synthase
In the reaction between Succinyl-CoA & Succinate…what molecules are reduced or generated?
A molecule of GTP is generated
GTP + ADP — GDP + ATP
What is GTP
Guanosine Triphosphate
Has a ribose sugar and 3 phosphates
Involved in energy transfer within the cell
What is Succinate oxidized to
Fumarate
What Enzyme is used to convert Succinate into Fumarate
Succinate Dehydrogenase
In the reaction between Succinate and Fumarate…what molecules are being generated or reduced
As FAD (its coenzyme) is reduced to FADH2
What is Fumarate hydrated to
Malate
Freely reversible reaction
What Enzyme is used to catalyze Fumarate into Malate
Fumarase
What is Malate oxidized to
Oxaloacetate
What is the last step of TCA cycle?
The conversion of Malate into Oxaloacetate
What Enzyme is used to convert Malate into Oxaloacetate
Malate Dehydrogenase
In the conversion of Malate into Oxaloacetate…what products are being generated or reduced
NAD+ is reduced into NADH
Reacton is positive, however rxn is driven in the direction of OAA by the highly exergonic Citrate Synthase reaction
What are the Single generated results of the Kreb Cycle
3 Molecules of NADH
1 FADH2
1 GTP
2 CO2
Since Glucose is split into 2 Pyruvate Compounds for each molecule of Glucose this Cycle has to run how many times and what are the Final Generated Compounds
Cycle runs X2: generating 6 Molecules of NADH 2 FADH2 2 GTP 4 CO2 Number of ATP produced= 12 ATP/Acetyl CoA oxidized
What happens to the FADH2 & NADH generated compounds
Both compounds are sent to the Electron Transport Chain for generation of ATP
What is PDH
Pyruvate Dehydrogenase
A multienzyme complex…contains 5 coenzymes that acti as carriers or oxidants for the intermediates
PDH supplies Substrate for TCA cycle
What are the ramifications if PDF is inactive?
Brain cells are unable to produce sufficient ATP (via TCA Cycle) therefore causing serious Centra Nervous System issues.
What is the medical condition caused as a result of inactive PDF and insufficient ATP formation in the CNS
Wernicke-Korsakoff :
Encephalopathy-psychosis syndrome due to Thiamine & Niacin Deficiency
Additionally : Alcohol abuse
Pyruvate is a potent inhibitor of
PDH kinase
Calcium (CA2+) is a strong activator of
PDH Phospatase
What happens in Pyruvate Dehydrogenase complex deficiency
The inability to convert Pyruvate to Acetyl CoA…causing Pyruvate to be shunted to lactate via lactate Dehydrogenase- causing issues for the brain
What are the symptoms of Pyruvate Dehydrogenase deficiency
Variable symptoms, including Neurodegeneration: muscles spasticity, and in the neonatal onset form, early death.
X linked dominant (X linked since both M & F are affected)
No treatment
Dietary restrictions to Carbohydrates & supplementation with thiamine may reduce symptoms in selected pt’s
Leigh Syndrome
Subacute necrotizing encephalomyelopathy a reare progressive neurodegenerativ edisordeer cause by defects in mitochondrial ATP production primarily as a result of mutation in genes nota code for proteins of PDH complex the electron transport chain or ATP synthase.
Both nuclear and mitochondrial DNA can be affected
Lipoamide
Lipoamide is an intermediate in glycolysis/gluconeogenesis, citrate cycle (TCA cycle), alanine, aspartate and pyruvate metabolism, and valine, leucine and isoleucine degradation
It is generated from dihydrolipoamide via the enzyme dihydrolipoamide dehydrogenase
