Understanding Acetyl CoA Formation from Pyruvate in Citric Acid Cycle - Prof. Yogarajah Jo, Study notes of Biochemistry

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Biochemistry: A Short Course

First Edition

Biochemistry: A Short Course

First Edition Tymoczko • Berg • Stryer © 2010 W. H. Freeman and Company

CHAPTER 17

Preparation for the Cycle

Glycolysis and Citric Acid Cycle Bridged via Pyruvate Dehydrogenase

Pyruvate is moved from the cytosol to the mitochondrion Matrix membrane permeability is critical Glycolysis are Cytosolic Enzymes While Mitochondria Complete Respiration

The Citric Acid CycleThe Citric Acid Cycle

Oxidizes Two-Carbon Units Oxidizes Two-Carbon Units

Acetyl Acetyl CO-ACO-A isis thethe fuelfuel forfor

the the citriccitric acidacid cycle.cycle. ThisThis

important important moleculemolecule isis formedformed

from from thethe breakdownbreakdown ofof

glycogen glycogen (the(the storagestorage formform ofof

glucose), glucose), fats,fats, andand manymany

amino amino acidsacids.. fatsfats containcontain

strings strings ofof reducedreduced two-carbontwo-carbon

units units thatthat areare firstfirst oxidizedoxidized

ThisThis irreversible reactionirreversible reaction is the link betweenis the link between glycolysis and the citric acid cycle. glycolysis and the citric acid cycle. NoteNote that, in the preparation of the glucose that, in the preparation of the glucose derivative pyruvate for the citric acid cycle, derivative pyruvate for the citric acid cycle, an oxidative decarboxylation takes place and an oxidative decarboxylation takes place and high-transfer-potential electrons in the form high-transfer-potential electrons in the form of NADH are captured. of NADH are captured. Thus, the pyruvateThus, the pyruvate dehydrogenase reaction has many of the key dehydrogenase reaction has many of the key features of the reactions of the citric acid features of the reactions of the citric acid cycle itself. cycle itself.

The Link betweenThe Link between Glycolysis and the Glycolysis and the Citric Acid Cycle. Citric Acid Cycle. Pyruvate produced by Pyruvate produced by glycolysis is converted glycolysis is converted into acetyl CoA, the into acetyl CoA, the fuel of the citric acid fuel of the citric acid cycle. cycle.

Electron Sink

Needed

Thiamine pyrophosphate (TPP) pulls in electrons

Pyruvate Dehydrogenase Complex

TheThe conversionconversion ofof pyruvatepyruvate intointo acetyl acetyl CoACoA consistsconsists ofof threethree steps: steps: decarboxylation, decarboxylation, oxidation,oxidation, andand transfer transfer ofof thethe resultantresultant acetylacetyl group group toto CoA.CoA.

Step 1: E1 (PDH) Decarboxylates Pyruvate

The oxidant in thisThe oxidant in this reaction is the reaction is the disulfide group of disulfide group of lipoamide, lipoamide, which iswhich is reduced to its reduced to its disulfhydryl form disulfhydryl form.. This reaction, also This reaction, also catalyzed by the catalyzed by the pyruvate pyruvate dehydrogenase dehydrogenase component E component E 11 ,, yields yields acetyllipoamide acetyllipoamide.

Step 3: E2 Oxidizes Hydroxyethyl- to

Acetyl-and Transfers Acetyl- to CoA

Dihydrolipoyl transacetylaseDihydrolipoyl transacetylase catalyzes catalyzes this reaction.this reaction. The energy-The energy- rich thioester bond is preserved as rich thioester bond is preserved as the the acetyl group is transferred toacetyl group is transferred to CoA. CoA. lipoamide lipoamide isis regeneratedregenerated byby dihydrolipoyl dehydrogenase dihydrolipoyl dehydrogenase (E(E (^33) ). Two). Two electrons electrons are transferred to an FADare transferred to an FAD prosthetic group of the enzyme prosthetic group of the enzyme andand then to NAD then to NAD ++ ..

Step 4-5: E3 Oxidizes Reduced

Dihydrolipoamide and Reduces NAD

+ Proteins tightly associated with FAD: Flavoproteins