Koc - Citric Acid Cycle Flashcards by John Castillo

Citric Acid Cycle Stages

Acetyl-CoA Production

Acetyl-CoA Oxidation

Electron Transfer and Oxidative Phosphorylation

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What is the source of majority of ATP (energy) production?

Complete oxidation of pyruvate in mitochondria

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Fate of Pyruvate: Anaerobic Condition

Lactate (LDH)

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Fate of Pyruvate: Amino Acid Synthesis?

Alanine

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Fate of Pyruvate: Aerobic Conditions

Acetyl-CoA (PDH complex driven)

Enters Citric Acid Cycle fo further oxidation

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Fate of Pyruvate: Anaplerotic Reaction / Gluconeogenesis

Oxaloacetate (Pyruvate Carboxylase)

Replenish citric acid cycle intermediates

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What is Acetyl-CoA oxidized to in the Citric Acid Cycle?

CO₂

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How is Pyruvate converted to Acetyl-CoA?

Oxidative Decarboxylation through Pyruvate Dehydrogenase Complex

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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

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What are three enzymes of PDH?

E1: Pyruvate Dehydrogenase

E2: Dihydrolipoyl Transacetylase

E3: Dihydrolipoyl Dehydrogenase

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TPP Deficiency

Thiamin - B1

Beriberi / Wenicke-Korsakoff

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NAD+ Deficiency

Niacin - B3

Pellagra (skin, psycho)

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FAD Deficiency

Riboflavin - B2

Cheilosis

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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

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What induces the Warburg Effect in cancer cells?

OXPHOS is inhibited due to highly active:

Pyruvate Dehydrogenase Kinase I, III

(inactivates PDH)

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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