CHAPTER 18
Preparation 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 dehydrogenase
complex
Figure 18.4
The link between glycolysis and the citric acid cycle
Pyruvate dehydrogenase
complex
One of the carbons in pyruvate
is oxidized to CO2.
The two electrons are eventually
given 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)
(decarboxylase)
TPP (Thiamine pyrophosphate)(Vit B1)
Dihydrolipoyl
transacetylase (E2)
Dihydrolipoyl
Dehydrogenase (E3)
Lipoic acid, HS-CoA
FAD, NAD+
Conversion of Pyruvate to Acetyl CoA
Decarboxylation
Pyruvate dehydrogenase E1 – decarboxylase reaction involving
the formation of HETPP and loss of CO2
Step 1
TPP: thymine pyrophosphate
Conversion of Pyruvate to Acetyl CoA
Oxidation
Pyruvate dehydrogenase E1– Oxidation reaction
involving the transfer of acetyl group to the lipoamide
group attached to the dihydrolipoyl transacetylase E2
Step 2
The prosthetic group, lipoic acid is attached to dihydrolipoyl
transacetylase via a lysine residue.
Note that the sulfur groups
have been reduced.
Energy rich thioester bond
is formed
Conversion of Pyruvate to Acetyl CoA
Formation of Acetyl CoA
dihydrolipoyl transacetylase(E2): Transfer of the acetyl group to
CoA forming acetyl CoA
Step 3
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 CoA
Oxidation 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 CoA
The rotating arm conversion
This entire conversion can be thought of as a swinging arm of the lipoamide
prosthetic group of E2.
Figure 18.7 Reactions of the PDH complex
Ensures the product
of one step does
not 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 18
Read Chapter 19