CHAPTER 18 Preparation for the Citric Acid Cycle
Jan 13, 2016
CHAPTER 18Preparation for the Citric Acid Cycle
Overview of the Citric Acid Cycle- The citric acid cycle is involved in the aerobic catabolism of carbohydrates, lipids, and amino acids
- Many of the intermediates of the cycle are starting points for many biosynthetic reactions:
Amino acids, fatty acids, and porphyrins
- Acetyl CoA is one of the key intermediates in the inter-conversion of molecules.
- Acetyl CoA is formed in the oxidative decarboxylation of pyruvate releasing CO2.
Figures 18.1 and 18.2
Figure 18.3 Mitochondrion
- Glycolysis occurs within the cytosolic region of a cell.
- Enzymes of the citric acid cycle are in the mitochondria of eukaryotes
Transport of Pyruvate from the cytosol into the Mitochondria
Pyruvate translocase transports pyruvate into the mitochondria in symport with H+
Pyruvate dehydrogenasecomplex
Figure 18.4 The link between glycolysis and the citric acid cycle
Pyruvate dehydrogenasecomplex
One of the carbons in pyruvateis oxidized to CO2.
The two electrons are eventuallygiven to one NAD+
Conversion of Pyruvate to Acetyl CoA- Pyruvate dehydrogenase complex is a multienzyme complex containing
3 enzymes + 5 coenzymes + other proteins
Coenzymes are needed for each of these steps
Components of the PDH Complex
Enzyme Coenzyme
Pyruvate dehydrogenase (E1) TPP (Thiamine pyrophosphate)(Vit B1)(decarboxylase)
Dihydrolipoyl Lipoic acid, HS-CoAtransacetylase (E2)
Dihydrolipoyl Dehydrogenase (E3) FAD, NAD+
Conversion of Pyruvate to Acetyl CoADecarboxylation
Pyruvate dehydrogenase E1 – decarboxylase reaction involvingthe formation of HETPP and loss of CO2
Step 1
TPP: thymine pyrophosphate
Conversion of Pyruvate to Acetyl CoAOxidation
The prosthetic group, lipoic acid is attached to dihydrolipoyl transacetylase via a lysine residue.
Pyruvate dehydrogenase E1– Oxidation reaction involving the transfer of acetyl group to the lipoamidegroup attached to the dihydrolipoyl transacetylase E2
Note that the sulfur groupshave been reduced.Energy rich thioester bondis formed
Step 2
Conversion of Pyruvate to Acetyl CoAFormation of Acetyl CoA
Step 3
dihydrolipoyl transacetylase(E2): Transfer of the acetyl group to CoA forming acetyl CoA
The dihydrolipoamide prosthetic group of E2 must be reoxidized back to the lipoamide form of E2 so that further acetyl transfers can take place.
Conversion of Pyruvate to Acetyl CoAOxidation of lipoamide
Dihydrolipoyl dehydrogenase E3: oxidation back to lipoamide.The flavin adenine dinucleotide prosthetic group undergoes reduction.
Steps 4 and 5
FADH2 must be re-oxidized back to FAD: this is done via reduction of NAD+
Conversion of Pyruvate to Acetyl CoAThe rotating arm conversion
This entire conversion can be thought of as a swinging arm of the lipoamideprosthetic group of E2.
Figure 18.7 Reactions of the PDH complexEnsures the productof one step doesnot diffuse into the medium
Regulation of the pyruvate dehydrogenase complex
Figure 18.9 Regulation of mammalian PDH complex occurs predominately by covalent modification(The Kinase and Phosphatase are regulated)
High ATP, acetyl CoA, NADH
High ADP, pyruvate
Assignment
Read Chapter 18Read Chapter 19