Biogenesis of morphine

 

Biogenesis of Morphine

Morphine is a naturally occurring alkaloid found in the opium poppy (Papaver somniferum). Its biosynthesis involves a complex series of biochemical reactions from the amino acid tyrosine. Below is a simplified version of the biogenesis of morphine:

1. Starting Material: L-Tyrosine

• Morphine biosynthesis begins with the amino acid L-tyrosine.
• L-tyrosine undergoes hydroxylation and decarboxylation to form L-DOPA (L-3,4-dihydroxyphenylalanine).

2. Formation of Norcoclaurine

• L-DOPA reacts with 4-hydroxyphenylacetaldehyde, forming the compound norcoclaurine.
• This reaction is catalyzed by the enzyme norcoclaurine synthase (NCS).

3. Conversion to Reticuline

• Norcoclaurine undergoes methylation (by norcoclaurine 6-O-methyltransferase) and several hydroxylation and methylation reactions to form (S)-reticuline.
• Reticuline is a key intermediate in the synthesis of many other alkaloids, including morphine.

4. Formation of Thebaine

• Through a series of enzyme-mediated reactions, (S)-reticuline is converted to (R)-reticuline, which undergoes several steps to produce thebaine.
• Thebaine is an important intermediate and is converted into morphine through additional reactions.

5. Conversion of Thebaine to Codeine

• Thebaine is first converted to codeinone, which is then reduced to codeine (a methylated form of morphine).

6. Conversion of Codeine to Morphine

• Codeine is demethylated by the enzyme codeine O-demethylase to form morphine.

Key Enzymes Involved:

• Tyrosine hydroxylase: Converts L-tyrosine to L-DOPA.
• Norcoclaurine synthase: Forms norcoclaurine from L-DOPA and 4-hydroxyphenylacetaldehyde.
• Methyltransferases: Involved in converting norcoclaurine to reticuline.
• Salutaridine synthase: Catalyzes a key step from reticuline to thebaine.
• Codeine O-demethylase: Converts codeine to morphine.

Summary:

• The biogenesis of morphine starts with L-tyrosine and proceeds through several steps, including the formation of key intermediates like L-DOPA, norcoclaurine, reticuline, and thebaine.
• The final steps involve the transformation of thebaine into codeine and then into morphine, with multiple enzyme-catalyzed reactions at each step.