Enzyme Synthesis Overview

Enzyme Synthesis

• The information about the primary sequence of an enzyme is found within the DNA.
• Enzymes are synthesized as part of a sequence of enzymes for metabolic pathways.
• Messenger RNA (mRNA) carries the instructions from genes to the ribosomes in the cytoplasm.
• Ribosomes, assisted by transfer RNA, assemble amino acids into the enzyme.
• Post-translational processing includes folding, amino acid modification, and proteolytic cleavage.
• Enzymes or proteins need to fold into the correct three-dimensional structure to become active.
• Folding processes are aided by:
  • Cis-trans isomerase for proline.
  • Disulfide bond-making enzymes.
  • Chaperonins: these are proteins that help other proteins fold and prevent aggregation.
• Proteins can target themselves to:
  • Cytoplasm, plasma membrane, outer membrane, periplasmic, and extracellular in bacteria.
  • Lysosomes, mitochondria, endoplasmic reticulum, Golgi complex, secretory vesicles, and plasma membrane in eukaryotes
• Translocation is the process of moving a protein to its destination.
• Signal Recognition Particle (SRP) detects signal sequences on newly synthesized proteins and directs them to the endoplasmic reticulum (ER) membrane.

Control of Enzyme Synthesis

• Most enzymes are not synthesized at maximum velocity all the time.
• Regulation of enzyme synthesis is controlled by metabolic needs and the state of the cell's development.
• The primary control point for enzyme synthesis is the copying of DNA genes into mRNA.
• Repressors are proteins that regulate enzyme synthesis in response to metabolic conditions.
• Inducers are molecules that increase enzyme synthesis when they are present.
• Repressors can be inactivated, allowing for enzyme synthesis.

Bacterial Enzyme Synthesis

• Jacob and Monod (1961) proposed that enzyme synthesis is regulated by regulator and operator genes.
• These genes control the rate of enzyme synthesis, with a repressor molecule acting as a link between them.
• Enzyme synthesis can be controlled by two main systems:
  • Inducible: The repressor molecule is synthesized in an active form, blocking the formation of specific proteins. An inducer will inactivate the repressor.
  • Repressible: The repressor is active only when combined with a corepressor and absence of the corepressor initiates new enzyme synthesis.

Enzyme Induction and Repression

• Enzyme induction is a process where the concentration of a substrate increases the concentration of enzymes needed to metabolize it.
• Enzyme repression is when the product of a metabolic pathway inhibits the synthesis of the enzymes for that pathway.
• Repressors bind to the operator gene and block transcription of the necessary genes.
• Repressors can be inactivated by inducers, removing the block on transcription.

Enzyme Turnover

• Proteins have different half-lives:
  • Most enzymes involved in metabolic regulation have short half-lives.
• Proteolytic enzymes are found throughout the cell.
• The rate of a protein's turnover can be determined by these factors:
  • Ubiquitination: A small protein called ubiquitin tags proteins for destruction.
  • Oxidation of amino acid residues: Damaged proteins can be degraded by proteases sensitive to oxidized residues.
  • PEST sequences: Sequences rich in proline, glutamate, serine, and threonine are often found in short-lived proteins.
  • N-terminal amino acid residue: The N-terminal residue can influence the rate of protein degradation.

Ubiquitination

• Ubiquitin conjugation involves three enzymes:
  • E1: Activates ubiquitin.
  • E2: Shuttle the activated ubiquitin to the target protein.
  • E3: Tags the target protein for degradation.
• Ubiquitin-specific proteases recognize and degrade the tagged proteins.

Oxidation of Amino Acid Residues

• Oxidative damage to proteins can lead to their degradation.
• Oxidation often occurs in residues like lysine, arginine, and proline.
• Specific proteases recognize and degrade oxidized proteins.

PEST Sequences

• Short-lived proteins often contain PEST sequences, which are rich in proline, glutamate, serine, and threonine.
• PEST sequences can increase the protein's susceptibility to degradation.

This quiz explores the intricate process of enzyme synthesis, highlighting the role of DNA, mRNA, and ribosomes in protein assembly. It covers post-translational modifications and the importance of correct folding mechanisms for protein functionality. Test your knowledge on how enzymes are produced and processed within cells.