Biosynthesis of Amino Acids PPT

Biosynthesis of Amino Acids PPT: Amino acid biosynthesis is a key cellular process where cells produce amino acids, the building blocks of proteins. It occurs mainly in the cytoplasm using intermediates from glycolysis, the citric acid cycle, and the pentose phosphate pathway. While essential amino acids must be obtained from the diet, non-essential ones are synthesized by the body. Nitrogen, often from ammonia or glutamate, is a vital component in the process. Enzymes catalyze each step and are tightly regulated to maintain balance. This process supports protein production, cell growth, and overall metabolic function.

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Biosynthesis of Amino Acids PPT

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AMINO ACID BIOSYNTHESIS
Synthesis of 20 Proteogenic Amino Acids in Microbes, Plants and Animals

Learning objectives:

  • Biosynthesis of Amino Acids
  • Understand the Metabolic Pathways that Synthesizes the 20 Proteogenic Amino Acids

Amino Acid Biosynthesis: Overview

  • Amino acid: Organic compound with both carboxyl (—COOH) and amino (—NH₂) group
  • Central α-carbon also bonded to hydrogen and side chain (R)
  • Building blocks of proteins
  • Synthesized from metabolite intermediates
  • Nitrogen is essential
  • Glutamine and Glutamate act as nitrogen sources
  • Bacteria and plants: synthesize all 20
  • Mammals: synthesize 11 (non-essential); others are essential (from diet)

Source of Nitrogen in Amino Acid Biosynthesis

  • Atmospheric N₂ → nitrate/nitrite → ammonia (NH₄⁺)
  • Ammonia → glutamate (via glutamate synthase)
  • Biological nitrogen fixation via nitrogenase:
    N₂ + 8H⁺ + 8e⁻ → 2NH₃ + H₂

Metabolic Pathways to Amino Acid Biosynthesis

  • All amino acids from:
    • Glycolysis
    • Citric acid cycle
    • Pentose phosphate pathway

Six Families of Amino Acids Based on Precursors
Family I: α-Ketoglutarate Derivatives

  • Glutamate, Glutamine, Proline, Arginine
  • Glutamate & Glutamine = major N sources in biosynthesis

Glutamate Synthesis (Plants & Microbes)

  • Enzyme: Glutamate synthase (α₂β₂ heterotetramer)
  • Electrons from NADPH (microbes) or ferredoxin (plants)

Glutamate Synthesis (All Organisms)

  • Enzyme: Glutamate dehydrogenase
  • Reaction: α-ketoglutarate + NH₄⁺ + NAD(P)H → Glutamate

Glutamine Synthesis

  • Enzyme: Glutamine synthase
  • Reaction:
    • Glutamate + ATP → γ-glutamyl-phosphate
    • γ-glutamyl-phosphate + NH₄⁺ → Glutamine

Proline Synthesis

  • From glutamate
  • Intermediate: Pyrroline-5-carboxylate (P5C)
  • Reduced to proline

Arginine Synthesis (Mammals)

  • Via ornithine and urea cycle
  • Involves N-acetyl glutamate → citrulline → argininosuccinate → arginine

Proline & Arginine in Mammals

  • Arginine → ornithine (by arginase) → glutamate-γ-semialdehyde → proline

Family II: 3-Phosphoglycerate Derivatives

  • Serine, Cysteine, Glycine

Serine Synthesis

  • 3-phosphoglycerate → 3-phosphohydroxypyruvate → 3-phosphoserine → serine

Glycine Synthesis

  • From serine via serine hydroxymethyl-transferase
  • Coenzyme: PLP, tetrahydrofolate

Cysteine Synthesis

  • Plants/Bacteria: From serine + sulfide (via sulfate reduction)
  • Mammals: From methionine + serine → cystathionine → cysteine

Family III: Oxaloacetate Derivatives

  • Aspartate, Asparagine, Methionine, Threonine, Lysine, Isoleucine

Aspartate & Asparagine Synthesis

  • Aspartate: Transamination of oxaloacetate
  • Asparagine: Amidation of aspartate (uses glutamine)

Lysine, Methionine, Threonine, Isoleucine Synthesis

  • From Aspartate β-semialdehyde
  • Branch points:
    • Lysine via diaminopimelate pathway
    • Methionine & threonine via homoserine
    • Threonine → Isoleucine

Family IV: Pyruvate Derivatives

  • Alanine, Valine, Leucine, Isoleucine

Valine & Isoleucine Synthesis

  • Pyruvate-TPP adduct
  • Valine: via α-ketoisovalerate
  • Isoleucine: via α-ketobutyrate

Leucine Synthesis

  • From α-ketoisovalerate
  • Involves β-isopropylmalate intermediate

Family V: Phosphoenolpyruvate + Erythrose-4-Phosphate Derivatives

  • Aromatic amino acids: Phenylalanine, Tyrosine, Tryptophan
  • Common intermediate: Chorismate

Chorismate Synthesis Pathway

  • PEP + E4P → DAHP → dehydroquinate → shikimate → shikimate-3P → EPSP → chorismate
  • EPSP synthesis is glyphosate-sensitive

Tryptophan Synthesis

  • Chorismate → anthranilate → PRPP adduct → indole ring → + serine → tryptophan

Tyrosine & Phenylalanine Synthesis

  • Chorismate → prephenate
  • Tyrosine: via hydroxyphenylpyruvate
  • Phenylalanine: via phenylpyruvate

Family VI: Ribose-5-Phosphate Derivative

  • Histidine
  • Precursors: PRPP, ATP (purine ring), Glutamine

Histidine Synthesis Highlights

  • PRPP + ATP → ring opening → imidazole ring formation
  • AICAR by-product enters purine biosynthesis
  • Histidine synthesis supports “RNA world” theory

References:

  • Stryer Biochemistry
  • Lehninger Principles of Biochemistry
  • Voet & Voet Biochemistry

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