Koc - Citric Acid Cycle Flashcards
Citric Acid Cycle Stages
Acetyl-CoA Production
Acetyl-CoA Oxidation
Electron Transfer and Oxidative Phosphorylation
What is the source of majority of ATP (energy) production?
Complete oxidation of pyruvate in mitochondria
Fate of Pyruvate: Anaerobic Condition
Lactate (LDH)
Fate of Pyruvate: Amino Acid Synthesis?
Alanine
Fate of Pyruvate: Aerobic Conditions
Acetyl-CoA (PDH complex driven)
Enters Citric Acid Cycle fo further oxidation
Fate of Pyruvate: Anaplerotic Reaction / Gluconeogenesis
Oxaloacetate (Pyruvate Carboxylase)
Replenish citric acid cycle intermediates
What is Acetyl-CoA oxidized to in the Citric Acid Cycle?
CO2
How is Pyruvate converted to Acetyl-CoA?
Oxidative Decarboxylation through Pyruvate Dehydrogenase Complex
What does the oxidative decarboxylation of Pyruvate to Acetyl-CoA require?
3 enzymes, 5 coenzymes
TPP, Lipoyllysine, FAD proesthetic groups
NAD+, CoA-SH co-substrates
What are three enzymes of PDH?
E1: Pyruvate Dehydrogenase
E2: Dihydrolipoyl Transacetylase
E3: Dihydrolipoyl Dehydrogenase
TPP Deficiency
Thiamin - B1
Beriberi / Wenicke-Korsakoff
NAD+ Deficiency
Niacin - B3
Pellagra (skin, psycho)
FAD Deficiency
Riboflavin - B2
Cheilosis
How is the Pyruvate Dehydrogenase complex regulated?
Phosphorylated = Inactive
Dephosphorylated = Active
Activate Phosphatase: Mg2+, Ca2+
Inhibit Kinase: Insulin, Pyruvate, NAD, CoA
(same result)
Inhibit Enzyme: NADH, Acetyl-CoA (end products)
Activate Kinase: Glucocorticoids, Insulin, Growth/thyroid hormones, Tyrosine kinase
What induces the Warburg Effect in cancer cells?
OXPHOS is inhibited due to highly active:
Pyruvate Dehydrogenase Kinase I, III
(inactivates PDH)
What is the final oxidative pathway in catabo;ism of carbs, amino acids, and fatty acids?
Citric Acid Cycle
What is net (per Acetyl CoA) in each turn of Citric Acid Cycle?
3 NADH
1 FADH2
1 GTP
How many ATP does the complete oxidation of one mole glucose produce?
30-32 ATP
What is first step of citric acid cycle?
2-C acetyl coa + 4-C OAA = 6-C citrate
What are the main intermediates in the Citric Acid Cycle?
- Oxaloacetate + Acetyl CoA = Citrate
- Citrate -> a-Ketoglutarate
- a-Ketoglutarate -> Succinyl CoA
- Succinyl CoA -> Fumarate
- Fumarate -> OAA
CAC: Reation 1: Citrate Synthase
Acetyl-CoA + OAA = Citrate
Enzyme: Citrate Synthase
Only reaction with C-C bond formation
RATE LIMITING STEP
Activity depends on [OAA]
High [OAA] drives forwards, favorable/irreversible
CAC: Reation 2: Aconitase
Citrate -(aconitase)- cis-Aconitase -(aconitase)- Isocitrate
Enzyme: Aconitase (isomerization rxn)
Unavorable/Reversible
Low [Product] pulls forward
Requires H2O
CAC: Reation 3: Isocitrate Dehydrogenase
Isocitrate -(isocitrate dehydrogenase)- {decarboxylation} - a-Ketoglutarate
Enzyme: Isocitrate Dehydrogenase
LOSE: CO2
GAIN: NADH
- - -
Favorable/Irreversible
Regulated by product inhibition, ATP
CAC: Reation 4: a-Ketoglutarate Dehydrogenase
a-Ketoglutarate -(a-Ketoglutarate dehydrogenase complex)- Succinyl-CoA
5-Carbon to 4-Carbon
Enzyme: a-Ketoglutarate Dehydrogenase
Produce: CO2
Produce: NADH
- - -
Net full oxidation of all carbons of glucose
Carbons lost come from OAA
Needs same 5 coenzymes as PDH complex
Regulated by product inhibition
Favorable/irreversible
CAC: Reation 4: a-Ketoglutarate Dehydrogenase is highly dependent on what?
Vitamin cofactors/coenzymes
Where do lost carbon atoms come from in the Citric Acid Cycle?
Oxaloacetate (OAA)
CAC: Reation 5: Succinyl-CoA Synthetase
Succinyl-CoA -(succinyl CoA synthetase)- Succinate
Requires energy
Substrate level phosphorylation
- - -
Produces GTP (makes ATP)
Low [Succinate] pulls forward
CAC: Reation 6: Succinate Dehydrogenase
Succinate -(Succinate Dehydrogenase)- Fumarate
Only membrane bound enzyme
- - -
Requires: FAD
Produces: FADH2
Reversible
[Product] pulls forward
CAC: Reation 7: Fumarase
Fumarate -(fumarase)- Malate
[Product] pulls forward
CAC: Reation 8: Malate Dehydrogenase
Malate -(malate dehydrogenase)- OAA
Oxidation of alcohol to ketone
Final Step
- - -
Require: NAD+
Produces: NADH
Highly UNFAVORABLE/reversible
What keeps [OAA] low in citric acid cycle?
Citrate Synthase
What is net of CAC per acetyl-coa?
2 CO2
3 NADH
1 FADH2
1 GTP
What anaplerotic reactions occur to provide CAC w/intermediates?
Pyruvate to OAA (Pyruvate Carboxylase)
Pyruvate to Malate (Malic Enzyme)
PEP to OAA (PEP Carboxykinase)
What type of amino acids can generate 3, 4, 5C intermediates of CAC?
Glucogenic
What enzymes are regulated in the CAC?
How are they regulated?
PDH Complex
Citrate Synthase
Isocitrate Dehydrogenase
a-Ketoglutarate Dehydrogenase Complex
ACTIVATE: Low Energy (AMP, CoA, NAD+, Ca2+)
INHIBIT: High Energy (ATP, NADH, Fatty Acids)
INHIBIT: End products (Citrate, succinyl-CoA)
High ATP/ADP , NADH/NAD+, Acetyl-CoA/CoA ratio effect on CaC?
Inhibits
