Lecture 11 - Biosynthesis of Amino Acids
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Transcript of Lecture 11 - Biosynthesis of Amino Acids
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Chem 454: Regulatory Mechanisms in Biochemistry
University of Wisconsin-Eau Claire
Chem 454: Regulatory Mechanisms in Biochemistry
University of Wisconsin-Eau Claire
Lecture 11 - Biosynthesis of Amino Acids
Lecture 11 - Biosynthesis of Amino Acids
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Biosynthetic pathways for amino acids, nucleotides and lipids are very old
Biosynthetic (anabolic) pathways share common intermediates with the degradative (catabolic) pathways.
The amino acids are the building blocks for proteins and other nitrogen-containing compounds
Biosynthetic pathways for amino acids, nucleotides and lipids are very old
Biosynthetic (anabolic) pathways share common intermediates with the degradative (catabolic) pathways.
The amino acids are the building blocks for proteins and other nitrogen-containing compounds
IntroductionIntroduction
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Nitrogen Fixation
Reducing atmospheric N2 to NH3
Amino acid biosynthesis pathways
Regulation of amino acid biosynthesis.
Amino acids as precursors to other biological molecules.
e.g., Nucleotides and porphoryns
Nitrogen Fixation
Reducing atmospheric N2 to NH3
Amino acid biosynthesis pathways
Regulation of amino acid biosynthesis.
Amino acids as precursors to other biological molecules.
e.g., Nucleotides and porphoryns
IntroductionIntroduction
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Nitrogen fixation is carried out by a few select anaerobic micororganisms
The carbon backbones for amino acids come from glycolysis, the citric acid cycle and the pentose phosphate pathway.
The L–stereochemistry is enforced by transamination of α–keto acids
Nitrogen fixation is carried out by a few select anaerobic micororganisms
The carbon backbones for amino acids come from glycolysis, the citric acid cycle and the pentose phosphate pathway.
The L–stereochemistry is enforced by transamination of α–keto acids
IntroductionIntroduction
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Microorganisms use ATP and ferredoxin to reduce atmospheric nitrogen to ammonia.
60% of nitrogen fixation is done by these microorganisms15% of nitrogen fixation is done by lighting and UV radiation.25% by industrial processes
Fritz Habers (500°C, 300 atm)
Microorganisms use ATP and ferredoxin to reduce atmospheric nitrogen to ammonia.
60% of nitrogen fixation is done by these microorganisms15% of nitrogen fixation is done by lighting and UV radiation.25% by industrial processes
Fritz Habers (500°C, 300 atm)
1. Nitrogen Fixation1. Nitrogen Fixation
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Enzyme has both a reductase and a nitrogenase activity.
Enzyme has both a reductase and a nitrogenase activity.
1. Nitrogen Fixation1. Nitrogen Fixation
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Contains a 4Fe-4S center
Hydrolysis of ATP causes a conformational change that aids the transfer of the electrons to the nitrogenase domain (MoFe protein)
Contains a 4Fe-4S center
Hydrolysis of ATP causes a conformational change that aids the transfer of the electrons to the nitrogenase domain (MoFe protein)
1.1 The Reductase (Fe protein)1.1 The Reductase (Fe protein)
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The nitrogenase component is an α2β2
tetramer (240 kD)
Electrons enter the P-cluster
The nitrogenase component is an α2β2
tetramer (240 kD)
Electrons enter the P-cluster
1.1 The Nitrogenase (MoFe Protein)1.1 The Nitrogenase (MoFe Protein)
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An Iron-Molybdenum cofactor for the nitrogenase binds and reduces the atmospheric nitrogen.
An Iron-Molybdenum cofactor for the nitrogenase binds and reduces the atmospheric nitrogen.
1.1 The Nitrogenase (MoFe Protein)1.1 The Nitrogenase (MoFe Protein)
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The ammonium ion is assimilated into an amino acid through glutamate and glutamine
Most amino acids obtain their α–amino group from glutamate by transamination.
The sidechain nitrogen of glutamine is the nitrogen source for the sidechain nitrogens of tryptophan and histidine.
The ammonium ion is assimilated into an amino acid through glutamate and glutamine
Most amino acids obtain their α–amino group from glutamate by transamination.
The sidechain nitrogen of glutamine is the nitrogen source for the sidechain nitrogens of tryptophan and histidine.
1.2 Assimilation of Ammonium Ion1.2 Assimilation of Ammonium Ion
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Glutamate dehydrogenaseGlutamate dehydrogenase
1.2 Assimilation of Ammonium Ion1.2 Assimilation of Ammonium Ion
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Glutamine synthetaseGlutamine synthetase
1.2 Assimilation of Ammonium Ion1.2 Assimilation of Ammonium Ion
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The biosynthetic pathways can be grouped into families:
The biosynthetic pathways can be grouped into families:
2. Amino Acid Biosynthesis2. Amino Acid Biosynthesis
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2.1 Essential Amino Acids2.1 Essential Amino Acids
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2.1 Essential Amino Acids2.1 Essential Amino Acids
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Transaminations:Transaminations:
2.2 Aspartate and Alanine2.2 Aspartate and Alanine
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Transaminations:Transaminations:
2.2 Aspartate and Alanine2.2 Aspartate and Alanine
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Amidation of aspartateAmidation of aspartate
2.3 Asparagine2.3 Asparagine
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Reduction of GlutamateReduction of Glutamate
2.4 Proline and Arginine2.4 Proline and Arginine
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Oxidation of 3–phosphoglycerateOxidation of 3–phosphoglycerate
2.5 Serine and Glycine2.5 Serine and Glycine
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Serine transhydroxymethylase produces glycine from serine
Serine transhydroxymethylase produces glycine from serine
2.5 Serine and Glycine2.5 Serine and Glycine
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2.6 Tetrahydrofolate2.6 Tetrahydrofolate
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2.5 Tetrahydrofolate2.5 Tetrahydrofolate
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2.5 Tetrahydro
-folate
2.5 Tetrahydro
-folate
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2.6 Methionine2.6 Methionine
Methylation of homocysteineMethylation of homocysteine
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Tetrahydrofolate does not have sufficient methyl transfer potential for many biosynthetic methylation reactions
Tetrahydrofolate does not have sufficient methyl transfer potential for many biosynthetic methylation reactions
2.7 S-Adenosylmethionine (SAM)2.7 S-Adenosylmethionine (SAM)
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2.7 Activated Methyl Cycle2.7 Activated Methyl Cycle
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DNA methylationDNA methylation
2.7 S-Adenosylmethionine2.7 S-Adenosylmethionine
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2.8 and 2.9 (skip)2.8 and 2.9 (skip)
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Example of essential amino acid synthesis
Involve Shikimate and Chorismate intermediates
Example of essential amino acid synthesis
Involve Shikimate and Chorismate intermediates
2.10 Aromatic Amino Acids2.10 Aromatic Amino Acids
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Chorismate:Chorismate:
2.10 Aromatic Amino Acids2.10 Aromatic Amino Acids
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2.10 Tyrosine and Phenylalanine2.10 Tyrosine and Phenylalanine
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2.10 Tryptophan2.10 Tryptophan
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Glycophate inhibites the enzyme that converts 5-Enolpyruvylshikimate 3–phosphate to chorismate.
Glycophate inhibites the enzyme that converts 5-Enolpyruvylshikimate 3–phosphate to chorismate.
2.10 Roundup2.10 Roundup
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2.11 Substrate Channeling (skip)2.11 Substrate Channeling (skip)
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Amino acid biosynthesis is regulated by feedback inhibition.
The first committed step in a biosynthetic pathway is usually to the one that is regulated.
Amino acid biosynthesis is regulated by feedback inhibition.
The first committed step in a biosynthetic pathway is usually to the one that is regulated.
3. Regulation of Amino Acid Biosynthesis
3. Regulation of Amino Acid Biosynthesis
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Example: Serine biosynthesis3–Phosphoglycerate dehydrogenase is inhibited by serine.
Example: Serine biosynthesis3–Phosphoglycerate dehydrogenase is inhibited by serine.
3. Regulation of Amino Acid Biosynthesis
3. Regulation of Amino Acid Biosynthesis
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Example: Serine biosynthesis
3–Phosphoglycerate dehydrogenase
Example: Serine biosynthesis
3–Phosphoglycerate dehydrogenase
3. Regulation of Amino Acid Biosynthesis
3. Regulation of Amino Acid Biosynthesis
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3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
Combination of feedback inhibition and activation
Combination of feedback inhibition and activation
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The regulatory binding domain for threonine deaminase is similar to that found in 3–phosphoglycerate dehydrogenase.
The regulatory binding domain for threonine deaminase is similar to that found in 3–phosphoglycerate dehydrogenase.
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Enzyme multiplicityExample: Aspartokinase
ThreonineMethionineLysine
Enzyme multiplicityExample: Aspartokinase
ThreonineMethionineLysine
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Cumulative feedback inhibitionExample: Glutamine Synthetase
Glutamine is the sources for nitrogen in the synthesis of
tryptophan histidinecarbamoyl phsphateglucosamine 6–phosphatecytidine triphosphateadenosine monophosphate
Cumulative feedback inhibitionExample: Glutamine Synthetase
Glutamine is the sources for nitrogen in the synthesis of
tryptophan histidinecarbamoyl phsphateglucosamine 6–phosphatecytidine triphosphateadenosine monophosphate
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Cumulative feedback inhibitionExample: Glutamine Synthetase
Cumulative feedback inhibitionExample: Glutamine Synthetase
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Cumulative feedback inhibitionGlutamine Synthetase activity is also modulated by and enzymatic cascade
Cumulative feedback inhibitionGlutamine Synthetase activity is also modulated by and enzymatic cascade
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Cumulative feedback inhibitionGlutamine Synthetase activity is also modulated by and enzymatic cascade
Cumulative feedback inhibitionGlutamine Synthetase activity is also modulated by and enzymatic cascade
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Cumulative feedback inhibitionThe regulatory protein P (PA or PD)
Cumulative feedback inhibitionThe regulatory protein P (PA or PD)
3.1 Regulation of Branched Pathways3.1 Regulation of Branched Pathways
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Amino acids are precursors for many biomolecules
Amino acids are precursors for many biomolecules
4. Amino Acid Derivatives4. Amino Acid Derivatives
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GlutathioneSulfhydryl buffer and antioxiidant
GlutathioneSulfhydryl buffer and antioxiidant
4.1 Glutathione4.1 Glutathione
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Nitric oxide is a short-lived signal molecule.
Formed from arginine
Nitric oxide is a short-lived signal molecule.
Formed from arginine
4.2 Nitric Oxide4.2 Nitric Oxide
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Porphyrins are synthesized from glycine an succinyl coenzyme A
Porphyrins are synthesized from glycine an succinyl coenzyme A
4.3 Porphyrins4.3 Porphyrins
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4.3 Porphyrins4.3 Porphyrins