Any time a living organism synthesises a chemical compound on its own, we term that activity ‘biosynthesis’ (or anabolism). These chemical reactions are different than ones we do in test tubes (in vitro) because biological systems have a host of mechanisms in place to drive energetically unfavourable reactions to completion, including enzyme catalysers (substances capable of initiating or speeding up a chemical reaction) and energy currency in the form of adenosine triphosphate or ATP (adenosine molecule bonded to three phosphate groups, present in all living tissue). Chemists mimic these processes by imbuing the system with heat, mechanical agitation, metal catalysers and more, but these are mere shadows on the wall compared to the vast beauty and efficiency of a biological synthetic pathway.
Biosynthesis of cannabinoids generally takes place in the plant cells of leaves, which makes sense. Building up these complex molecules involves a large amount of energy expenditure and leaves are the main powerhouse of the plant. Cannabinoids are also big and bulky; Tetrahydrocannabinol (THC) alone requires 21 carbon atoms. All this carbon matter has to come from somewhere and in the case of plants, this matter comes right from the air, from carbon dioxide (CO2). Plants take up CO2 in their leaves, some of it becoming photosynthesised into molecular oxygen (O2) and some being catabolised (degradative metabolism) into simple organic compounds for use throughout the plant.
Figure 1. Isopentyl diphosphate (1) and dimethylallyl diphosphate (2) are the precursor molecules of all terpenoids. They are shunted into the cannabinoid pathway by enzymatically catalysing their addition into geranyl diphosphate (3).
Interestingly, cannabinoid biosynthesis is a branch of terpenoid biosynthesis, sharing the same precursor molecules and pathways (Figure 1). There is more than one pathway to create these precursors. Once these precursors are made, they are shunted into the cannabinoid pathway by a series of enzymatic reactions which produce the penultimate cannabinoid precursor Cannabigerolic acid, or CBGa (Figure 2).
Figure 2. Geranyl diphosphate (3) and olivetolic acid (4) are combined to form CBGa (5).
From there, the cannabinoids that we have discovered seem to differentiate mostly via non-catalysed modifications to the skeletal structure. This explains the similar structure shared by all cannabinoids. These modifications include decarboxylation (loss of CO2 moiety [part of a molecule]), isomerisation (structural rearrangement without change in chemical composition) and oxidation (loss of electrons). There are also three enzymes that specifically modify CBGa into more specific cannabinoid moieties, including the all-important Tetrahydrocannabinolic acid (THCa) and Cannabidiolic acid (CBDa) (Figure 3).
Figure 3. CBGa is modified by three particular enzymes, producing Cannabichromenic acid (CBCa) (6), THCa (7), or CBDa (8). The numbers surrounding the structures of 6 and 7 help identify carbon atoms, facilitating understanding and communication.