Section 8 - The Citric Acid Cycle
Chapter 18 - Preparation for the Cycle
● Pyruvate in presence of oxygen → converted into acetyl coenzyme
A (Acetyl CoA)
○ Enters the citric acid cycle
■ 2-carbon acetyl units (acetyl CoA)
■ Bind to a 4-carbon acceptor molecule → 6-carbon
molecule
■ 2 carbon units are oxidized to CO2 → 4-carbon
molecule
● Acceptor molecule is regenerated
18.1 - Pyruvate Dehydrogenase Forms Acetyl
Coenzyme A from Pyruvate
● Glycolysis → in the cytoplasm
● Citric acid cycle → in the mitochondria
○ Pyruvate must be transported into the mitochondria
○ Pyruvate is oxidatively decarboxylated by the pyruvate
dehydrogenase complex to form acetyl CoA
○ Pyruvate + CoA + NAD+ → acetyl CoA + CO2 + NADH +
H+
● Irreversible conversion of pyruvate into acetyl CoA is the link
between glycolysis and the citric acid cycle → decisive reaction
Chapter 19 - Harvesting Electrons from the Cycle
● The catabolic function of the citric acid cycle is the harvesting of
high-energy electrons from carbon fuels
19.1 The Citric Acid Cycle Consists of Two Stages
● 2-carbon acetyl unit condenses with a 4-carbon component
(oxaloacetate) → 6-carbon tricarboxylic acid (citrate)
● Citrate releases 2 CO2 → 4-carbon compound remains
● 4-carbon compound → oxidized to regenerate oxaloacetate
● Oxaloacetate initiates another round of the cycle
, ● Citric acid cycle → does not generate much ATP nor oxygen as a reactant
○ It captures high-energy electrons from citrate and its metabolites and uses
them to form NADH and FADH2
■ Each electron carrier yields 9 ATP when they are oxidized by O2 in
oxidative phosphorylation
● Citric acid cycle → 2 stages
○ Stage 1
■ 2 carbon atoms are introduced by coupling to oxaloacetate → forms
citrate → 2 CO2 released
○ Stage 2
■ The resulting 4-carbon molecule → metabolized to regenerate
oxaloacetate
19.2 Stage One Oxidizes Two Carbon Atoms to Gather Energy-Rich
Electrons
● Oxaloacetate + acetyl CoA → Citrate
○ Catalyzed by citrate synthase
○ Citryl CoA → energy-rich because it contains the thioester that originated in
acetyl CoA
■ The hydrolysis of the thioester powers the synthesis of a new
molecule from 2 precursors
● The mechanism of citrate synthase prevents undesirable reactions
○ Side reactions must be minimized
○ Mammalian citrate → identical subunits
■ Active site → cleft between the large and small domains of a subunit
○ Citrate synthase → binds substrate in a sequential, ordered fashion
■ Oxaloacetate binds first, followed by acetyl CoA
Chapter 18 - Preparation for the Cycle
● Pyruvate in presence of oxygen → converted into acetyl coenzyme
A (Acetyl CoA)
○ Enters the citric acid cycle
■ 2-carbon acetyl units (acetyl CoA)
■ Bind to a 4-carbon acceptor molecule → 6-carbon
molecule
■ 2 carbon units are oxidized to CO2 → 4-carbon
molecule
● Acceptor molecule is regenerated
18.1 - Pyruvate Dehydrogenase Forms Acetyl
Coenzyme A from Pyruvate
● Glycolysis → in the cytoplasm
● Citric acid cycle → in the mitochondria
○ Pyruvate must be transported into the mitochondria
○ Pyruvate is oxidatively decarboxylated by the pyruvate
dehydrogenase complex to form acetyl CoA
○ Pyruvate + CoA + NAD+ → acetyl CoA + CO2 + NADH +
H+
● Irreversible conversion of pyruvate into acetyl CoA is the link
between glycolysis and the citric acid cycle → decisive reaction
Chapter 19 - Harvesting Electrons from the Cycle
● The catabolic function of the citric acid cycle is the harvesting of
high-energy electrons from carbon fuels
19.1 The Citric Acid Cycle Consists of Two Stages
● 2-carbon acetyl unit condenses with a 4-carbon component
(oxaloacetate) → 6-carbon tricarboxylic acid (citrate)
● Citrate releases 2 CO2 → 4-carbon compound remains
● 4-carbon compound → oxidized to regenerate oxaloacetate
● Oxaloacetate initiates another round of the cycle
, ● Citric acid cycle → does not generate much ATP nor oxygen as a reactant
○ It captures high-energy electrons from citrate and its metabolites and uses
them to form NADH and FADH2
■ Each electron carrier yields 9 ATP when they are oxidized by O2 in
oxidative phosphorylation
● Citric acid cycle → 2 stages
○ Stage 1
■ 2 carbon atoms are introduced by coupling to oxaloacetate → forms
citrate → 2 CO2 released
○ Stage 2
■ The resulting 4-carbon molecule → metabolized to regenerate
oxaloacetate
19.2 Stage One Oxidizes Two Carbon Atoms to Gather Energy-Rich
Electrons
● Oxaloacetate + acetyl CoA → Citrate
○ Catalyzed by citrate synthase
○ Citryl CoA → energy-rich because it contains the thioester that originated in
acetyl CoA
■ The hydrolysis of the thioester powers the synthesis of a new
molecule from 2 precursors
● The mechanism of citrate synthase prevents undesirable reactions
○ Side reactions must be minimized
○ Mammalian citrate → identical subunits
■ Active site → cleft between the large and small domains of a subunit
○ Citrate synthase → binds substrate in a sequential, ordered fashion
■ Oxaloacetate binds first, followed by acetyl CoA
