Monday, 28 December 2009

Secondary Metabolites and Secondary Metabolism


'Secondary Metabolites and Secondary Metabolism' may not seem a very exciting title. But secondary metabolites certainly can be exciting, as Aunt Epp's vaginal pheromones demonstrated.

Secondary metabolites have been responsible for wars and the growth and destruction of empires. The search for supplies of secondary metabolites led to the discovery of America.

Secondary metabolites have also saved millions of lives and inspired cultural and artistic movements. They are essential ingredients of religious rituals, and causes of major social problems. They are intimately involved with traditional healing folklore including what was once classed as witchcraft.

Amanita muscaria - as used in shamanistic rituals

Primary and Secondary Metabolites
So what are secondary metabolites, and how do they differ from the mundane primary metabolites? Well, according to Wiki:

'Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of organisms. Unlike primary metabolites, absence of secondary metabolites does not result in immediate death, but rather in long-term impairment of the organism's survivability, fecundity, or aesthetics, or perhaps in no significant change at all. Secondary metabolites are often restricted to a narrow set of species within a phylogenetic group.'


'A primary metabolite a metabolite is directly involved in normal growth, development, and reproduction.'

Opium poppy

In other words, primary metabolites are the boring but essential bog-standard amino acids, fats, sugars etc found in most living things, whereas secondary metabolites are unusual compounds restricted to just a few species.

In the case of pheromones, they are usually unique to a single species, because if you're a lonely lady silk moth trying to attract the insect world's equivalent of Mr Right, you don't want a gang of horny dung beetles turning up in response to your amorous secretions.

The Penicillium fungus and penicillin molecule

As well as pheromones, natural products include:
  • Plant based drugs, both beneficial and narcotic. Eg opiates, digitalis, quinine.
  • Fungal, plant and amphibian entheogens such as psilocybin, bufotenine and ergot.
  • Antibiotics such as penicillin and streptomycin.
  • Flower scents and other essential oils.
  • Plant and animal pigments such as indigo and Tyrian Purple
  • The active ingredients of herbs and spices
  • Alkaloid poisons and insecticides.
  • Venoms
Flower petal fragrances

As the University of Basel's website explains:

'Over 200'000 secondary metabolites have been identified to date. This number, however, represents only a fraction of the biosynthetic capabilities of living organisms. The enormous structural diversity of natural products is the result of co-evolutive selection processes. One can reasonably assume that most of the secondary metabolites synthesized by an organism have some purpose for the producer. Natural products have evolved to interact with proteins of target organisms, typically lower organisms such as bacteria, fungi, insects etc. Given the highly conserved nature of numerous proteins and protein domains, structurally homologous proteins exist in humans even though their function may sometimes have changed. It is not accidental that natural products interact with human proteins and, therefore, represent a unique pool of molecules with drug-like properties.'

Foxglove, source of the medicinal drug digitalis

So we can generally assume that secondary metabolites (sometimes known by the rather vague term 'natural products') are usually involved in interaction with other individuals. In the case of pheromones this may be to interact with a member of the same species, but mostly these metabolites interact with members of other species:
  • Penicillin kills off bacteria which are competing with the Penicillium fungus for food.
  • Pleasant tasting flavor compounds in fruit attract seed dispersers.
  • Bitter and poisonous alkaloids in leaves deter grazers.
  • Flower colors and scents attract pollinators

Actinomyces cultures - prolific producers of antibiotics

Some secondary metabolites don't affect other species but protect against severe physical and chemical conditions. Some plant pigments protect against UV. The siderochromes scavenge iron and allow its uptake from otherwise insoluble sources.

Nutmeg - source of essential oil flavorings

Cultural effects
The search for easier routes to the spice producing countries was the main motivation for the voyages of discovery. Pepper, cloves and nutmeg were especially prized.

Pepper - active ingredient piperine

Columbus' voyage was primarily intended to discover a fast route to the Spice Islands - not to explore new lands.

The arts
Mood altering substance have been used by poets and artists throughout the ages.

The hallucinogenic absinthe (wormwood) was popular among the Parisian avant garde at the end of the 19th century, and fungal metabolites such as psilocybin and LSD were responsible for the psychedelic movement of the 1960's

1960's Psychedelia

Ergot - raw material for LSD

Evolution of secondary metabolites.
So how did this huge range of compounds evolve? The usual theory is that they were originally 'shunt-metabolites' - waste products produced in response to metabolic imbalances. If a plant accumulates excessive primary metabolites, for example certain amino acids, then it has no way of excreting the surfeit, which can become toxic. Since plants and fungi can't pee or poo their waste products out, the best solution is to transform these small molecules to less toxic forms by reacting them together to give larger molecules and then storing them in the leaves or roots. Some secondary metabolites may have stayed at this stage.

The metabolic pathways and enzymes needn't in the first instance be all that specific: as long as they get rid of waste product it doesn't matter what they produce. That's why organisms often produce a range of similar secondary metabolites rather than a single compound.

However, some of these stored metabolites might have ecological effects, for example making the plant less attractive to grazers, or in the case of volatile compounds by making a particular species more easily recognisable by its pollinators or seed distributors. Once these ecological interactions begin, there is selective pressure for the secondary metabolites to evolve and change to become more efficient.

- Sean Robsville


Buddhism, Shamanism and the use of entheogens

Wiccan Love Potions, Women's Pheromones and Ethnopharmacology

Cauldron, Chalice and Grail Symbolism 




Dr. Lalita Calabria said...

Very cool post! Check out my blog about phytochemistry:

Anonymous said...

Just though you might like to check your picture of Actinomyces, as it looks like you may have an image of Nocardia... Great post otherwise

Cristin said...

Metabolites are the products of enzyme-catalyzed reactions that occur naturally within cells. The term metabolite is usually used to describe small molecules, while broader application is often practiced. Metabolites