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PUCO Opt 500- TCA Cycle
Dr. Hua, lecture8
21
Biochemistry
Professional
09/24/2011

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Term
Summary of TCA Cycle
Definition
  • Also known as Tricarboxylic Acid Cycle (TCA Cycle) and Krebs Cycle
  • Takes place in mitochondria
  • Utilizes acetyl-CoA, which itself is generated from pyruvate by pyruvate dehydrogenase enzyme
  • Each acetyl-CoA generates = 3 NADH, 1 FADH2, and 1 GTP
  • NADH and FADH2 are responsible for delivering electrons to Electron Transport Chain to generate energy via oxidative phosphorylation.
Term
Equation and Products of TCA
Definition

Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi → 2 CO2 + 3 NADH + 1 FADH2 + 1 GTP + CoA

 

Products: 2 CO2

               3 NADH

                 1 FADH2

             1 GTP

           CoA

Term

Steps in TCA:

Citric Synthase

Definition
first step, inhibited by ATP
Term
Isocitrate dehydrogenase
Definition
  • Rate-limiting enzyme
  • Activated by: ADP
  • Inhibited by: ATP, NADH
Term
. α-Ketoglutarate dehydrogenase
Definition
Inhibited by: Succinyl-CoA, ATP, and NADH
Term
Pyruvate Dehydrogenase
Definition
In matrix: pyruvate is converted to acetyl CoA (2-C substrate) by the pyruvatedehydrogenase complex (focus on E1)
Term
thyamine pyrophosphate
Definition
Coenzyme needed by pyruate dehydrogenase in order to be activated
Term
PDH Kinase
Definition
Inhibits pyruvate dehydrogenase, allosterically activated by ATP (so ATP activates the inhibitor, making it an indirect antagonist to pyruvate dehydrogenase)
Term
PDH Phosphatase
Definition
Activates phyruvate dehydrogenase, its activity is also increased by Ca2++, stimulating E1 activity
Term
Citrate Synthesis
Definition

made from acetyl CoA, and inhibited by its product (citrate)

 

Once made, it is isomerized by aconitase into isocitrate

 

Oxidation rxn yields decarboxylation of isocitrate

this is one of rate limiting steps that will yield 1st of 3 NADH molecules

1st release of CO2

Term
Decarboxylation of ketoglutarate
Definition

converted to succinyl CoA

 

will release 2nd CO2 and 2nd NADH

Term

succinyl CoA

succinate

fumarate

Definition

 

cleaved by Succinatethiokinase (yields 1 ATP) to succinate.
 
Succinate is oxidized to fumarate (by succinate dehydrogenase)
fumarate is hydrated to malate by fumarase
Term
Oxidation of Malate
Definition

oxidized to oxaloacetate by malate dehydrogenase.

- makes 3rd and FINAL NADH of cycle

Term

Intermediates of TCA Cycle

 

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Definition
Citrate- Isocitrate- Ketoglutarate- Succinyl CoA- Succinate- Fumarate- Malate- Oxaloacetate
Term
ATP Yields: TCA cycle
Definition

Pyruvate to Acetyl CoA = 1 NADH = 3 ATP

Steps 3 = NADH = 3 ATP
Steps 4 = NADH = 3 ATP
Steps 8 = NADH = 3 ATP

  NET ATP from = NAD+ = 9 ATP

Step 6 is another oxidation involving the coenzyme FADH2.

   Step 6 = FADH2 = 2 ATP

Step 5 = 1 ATP

15 ATP/Pyruvate * 2= 30 ATP!!

Term
Energy Yields
Definition

Glycolysis yields 6 ATP

 

TCA= 30 ATP

 

Glycolysis (anaerobic) yields 2 ATP

Term
Conversion of pyruvate to acetyl CoA and CO2
Definition

This is irreversible and involves help from lipoic acid.

Activated when PDH is phosphorylated by PDH kinase in presence of ATP

This also occurs in cytosol and in presence of an enzyme called biotin

Term
Pentose Phosphate Pathway & NADPH
Definition

- Pathway that occurs in cytosol

- Involves two reversible oxidative rxns to form sugar phosphate ring molecules that are involved in nucleotide synthesis.

- No ATP is used or made in this process!

- povides most of body's NADPH

Term

Pentose Phosphate Path-

Irreversible Oxidative Pathways

Definition

that lead to the formation of ribulose 5-phosphate, CO2, and 2 molecules of NADPH for each molecule of glucose 6-phosphate oxidized

 

Important for the liver, adrenal cortex, and erythrocytes

Term
Dehydrogenation of glucose 6-phosphate
Definition

G6P is made to 6-phosphogluconolactone by G6PD and the conezyme NAD+.

 

6-PGL is then oxidatively docarboxylated into pentose sugar-phosphate, CO2, and NADPH

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