Download 26_Lecture - Ventura College

Organic Chemistry
6th Edition
Paula Yurkanis Bruice
Chapter 26
The Organic
Chemistry
of the Metabolic
Pathways
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Metabolism is the set of reactions living organisms
carry out to obtain energy and to synthesize complex
molecules
catabolism: complex molecules
simple molecules + energy
anabolism: simple molecules + energy
complex molecules
Metabolism is the combination of
catabolism and anabolism
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The Four Stages of Catabolism
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• Compounds that can enter the citric acid cycle are
citric acid cycle intermediates, acetyl-coA, and
pyruvate.
• Pyruvate enters the cycle by being converted to
acetyl-CoA.
• Acetyl-CoA is the only non–citric acid cycle
intermediate that can enter the citric acid cycle by
being converted to citrate.
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Metabolic Energy Is Measured in Terms
of Adenosine Triphosphate (ATP)
ATP is the universal carrier of chemical energy
The energy released from hydrolysis of ATP converts
endergonic reactions into exergonic reactions
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Thermodynamics of glucose-6-phosphate formation:
A phosphoanhydride bond is broken in this reaction
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Mechanism for a phosphoryl transfer reaction:
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Without ATP, phosphorylation cannot occur:
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Three Mechanisms for Phosphoryl Transfer Reactions
• Each of the three phosphorus atoms of ATP can
undergo nucleophilic attack.
• Each mechanism places a different phosphoryl
group on the nucleophile.
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The pyrophosphate product is further hydrolyzed to
ensure irreversibility of the reactions:
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The “High-Energy” Character
of Phosphoanhydride Bonds
The hydrolysis of a phosphoanhydride bond is highly
exergonic
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Three Factors Contribute to the Greater Stability
of ADP and Phosphate Compared to ATP
1. Greater electrostatic repulsion in ATP
2. More solvation stabilization in the products
3. Greater electron delocalization in the products
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ATP reacts slowly in the absence of enzymes because
the negative charges on ATP decrease leaving ability
In an enzyme active site, positive centers decrease
the overall negative charge
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The Catabolism of Fats
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• A kinase is an enzyme that puts a phosphoryl group
on its substrate.
• A dehydrogenase is an enzyme that oxidizes its
substrate.
• Dihydroxyacetone phosphate enters the glycolytic
pathway and is broken down further.
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Mechanism for the conversion of glycerol-3-phosphate
to dihydroxyacetone phosphate:
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A fatty acid has to be activated before it
can be metabolized:
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The fatty acyl-CoA is converted to acetyl-CoA via
b-oxidation:
1.
2.
3.
4.
acyl-CoA dehydrogenase
enoyl-CoA hydratase
3-L-hydroxyacyl-CoA dehydrogenase
b-ketoacyl-CoA thiolase
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Reaction mechanisms
Conjugate addition of water:
A retro-Claisen condensation:
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The Catabolism of Carbohydrates
In the first stage of carbohydrate catabolism,
polysaccharides are enzymatically hydrolyzed to
glucose molecules:
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Glucose is converted to two molecules of pyruvate by the
10-step process known as the glycolytic pathway:
1. Glucose is converted to glucose-6-phosphate (Section 26.1)
2. Glucose-6-phosphate isomerizes to fructose-6-phosphate
(Section 24.9)
3. ATP puts a second phosphoryl group on fructose-6-phosphate
to yield fructose-1,6-diphosphate
4. The reverse of an aldol reaction (Section 24.9)
5.
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Mechanism of step 5:
Compare this mechanism with the enediol
rearrangement shown in Section 22.5
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6. Glyceraldehyde-3-phosphate is oxidized by NAD+ to yield 1,3diphosphoglycerate (Section 25.1)
7. ATP formation
8. Isomerization
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9. Dehydration
10. ATP formation
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Glycolysis
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The Fates of Pyruvate
Aerobic conditions:
Anaerobic conditions:
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Yeast converts pyruvate to ethanol:
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The Catabolism of Proteins
The first stage of protein catabolism is enzymatic
hydrolysis of proteins to amino acids:
Amino acids are then converted to acetyl-CoA,
pyruvate, or citric acid cycle intermediates
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An Example of Amino Acid Catabolism
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The Citric Acid Cycle
The acetyl group of each molecule of acetylCoA is formed by the catabolism of fats,
carbohydrates, and amino acids
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The Citric Acid Cycle
Contains Eight
Reactions
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1. Carbonyl addition and hydrolysis (Sections 18.2 and 17.5)
2. Dehydration and conjugate addition of water (Section 18.18)
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3. Oxidation and decarboxylation (Section 19.19)
4. Oxidation and decarboxylation (Section 25.3)
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5. Addition–elimination reaction followed by phosphate transfer to
GDP
6. FAD oxidizes succinate to fumarate (Section 25.2)
7. Conjugate addition of water to the double bond of fumarate
forms (S)-malate (Section 5.20)
8. Oxidation of the (S)-malate by NAD+ forms oxaloacetate,
returning the cycle to its starting point
Reactions 6, 7, and 8 in the citric acid cycle are similar to reactions
1, 2, and 3 in β-oxidation of fatty acids (Section 26.6)
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Oxidative Phosphorylation
For every acetyl-CoA that enters the citric acid cycle,
11 molecules of ATP are formed from NADH and
FADH2, and one molecule of ATP is formed in the cycle
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