Our body is a complicated system of different organs, compartments and control stations.
If you compare it to a highly-developed city with its different districts, logistic intersections and administrative centres,
biomolecules could be regarded as an indispensable part of the crew that keeps the city running.
And the crew is busy.
Small molecules serve as nutrients providing both energy and building blocks for the city’s maintenance, growth and development.
As neurotransmitters, hormones or pheromones they are engaged in the city’s communication service.
And as vitamins they support essential tasks of the city’s administration.
As different as all these small members of the city’s management crew are in function and chemical structure,
they have one thing in common.
Their atomic mass is lower than 900 Dalton, a threshold that is far exceeded by large molecules such as DNA or proteins.
Small biomolecules may either be produced by the body itself or enter it via inhalation, absorption through the skin or food.
So with every bite that enters our mouth we take up large amounts of small molecule nutrients
such as carbohydrates and lipids, which are both fuel and building material for our body.
The large amount of carbon in carbohydrates and lipids is of crucial importance for obtaining energy:
Through different chemical pathways our body converts complex, carbon-based macronutrients into smaller, stable compounds –
as if a chemical puzzle fell into small pieces to generate energy.
Lipids also fulfil constructive tasks such as building cell membranes.
No other group of small molecules has led to more awards than vitamins.
Eight Nobel laureates owe their Prizes directly to work on the discovery, isolation or structural characterization of novel vitamins.
It started with the 1929 Nobel Award in Physiology or Medicine,
which went to Frederick Hopkins and Christiaan Eijkman for their discovery of vitamin A and B1.
Although the scientists were not able to isolate both substances,
they pointed out that food containing them such as milk and brown rice could cure certain conditions arising from an unbalanced diet.
Richard Kuhn 1952:
„Normally, all mammals, for a short or longer length of time after birth, feed exclusively on their mother’s milk.
Evidently, breast milk contains everything that is essential for the newborn to thrive.
When, in 1909, Wilhelm Stepp in Strassburg and then Frederick Gowland Hopkins in England tried to raise young mice and young rats
on a diet consisting of highly purified protein, fat, carbohydrate and mineral salts, they found it did not work.
The animals died.
By contrast, the animals developed well when milk was added to this diet.
That is more or less what you might expect.
But the experiments also led to an unexpected observation, namely that even “astonishingly small amounts of milk”, as Hopkins put it,
were sufficient to supply the animals with what he himself called accessory nutrients, but which soon became known as vitamins.“
Today we know 13 different vitamins; they are classified by their biological and chemical activity.
They work, for example, as cofactors for enzymes or as antioxidants.
The latter protect the cells against free radicals which can cause severe damage.
Antioxidants make sure that the traffic in our body-system runs smoothly
as does the most famous vitamin of all, vitamin C, also known as ascorbic acid.
A lack of it can cause scurvy, once prevalent among sailors.
Long sought after since the middle of the 19th century, it was first isolated accidently by the Hungarian scientist Albert von Szent-Györgyi.
He received the Nobel Prize in Physiology or Medicine in 1937
while Walter Howarth received the Nobel Prize in Chemistry for synthesizing vitamin C in 1934.
Besides nutrition signal transduction is another important field starring small molecules.
For many years scientists had intensely debated whether neural connections were electrical or chemical in nature
until the pharmacologist Otto Loewi in 1920 demonstrated the hybrid electrochemical nature of nervous signalling in a famous experiment.
He isolated two still beating frog hearts in separate vessels containing a saline solution.
In one heart he electrically stimulated the vagus nerve which slowed down the heartbeat.
Loewi then took some of the solutions surrounding this heart and poured it over the second heart.
Although this heart had not been electrically stimulated, it immediately began to beat more slowly, too.
Obviously, the electrical stimulation had triggered the release of a chemical substance into the solution that acted as a neurotransmitter.
Later it turned out that this small molecule was acetylcholine, the principal neurotransmitter of the parasympathic nervous system.
In 1936 Loewi received the Nobel Prize in Physiology or Medicine together with Henry Dale, who had first identified acetylcholine in 1914.
Nobel Laureate Erwin Neher, who received a shared Prize for his work on ion channels in 1991,
summarized current knowledge on synaptic transmission in one of his Lindau lectures as follows:
Erwin Neher 2011: “And this information, of course, when it was combined with the electron microscopic evidence at that time
that in the nerve terminals there are this little structures, these little granules called synaptic vesicles,
this combined led to our current understanding of what a synaptic transmission is,
namely that a nerve impulse causes the influx of calcium ions.
I mean this was… An underlying observation was that the strength of the signal
is so critically dependent on extracellular calcium concentration.
So this is calcium entering the nerve terminal as a consequence of the action potential.
The calcium makes vesicles fuse with the plasma membrane
and the vesicles are filled with neurotransmitter which defuses to the postsynaptic membrane.
The neurotransmitter opens channels in the postsynaptic membrane
and so this again causes an electrical signal in the postsynaptic membrane.
So we have this relatively complex process, an electrical signal being translated into a chemical signal and back again to an electrical signal.”
Long distance signal transduction within our body is conducted by hormones,
which show a wide range of structural variety and are therefore involved in many physiological processes.
Around 150 of them are known today.
Hormones are synthesized for example in the brain, the thyroid gland and the sexual organs.
Many of them are small biomolecules.
The first Nobel Prize for research on small molecule hormones was awarded
to the German scientist Adolf Butenandt in 1939 for his work on sex hormones.
He had isolated the sex hormone oestrone, which belongs to the class of steroids.
Other hormones belong to different chemical classes.
Our olfactory system is also sensitive for small molecule signals.
It is able to recognize a set of around 10.000 odours which are all composed from a number of 1.000 small molecule odorants.
These odours are kind of all-rounders.
Some may warn us of immediate dangers, others tells us about the quality of food
or, in the case of pheromones, even with whom we want to have sex.
Adolf Butenandt 1960: „I would like to describe an elegant experiment from the recent literature which was carried out on Chinese silkmoths.
Males of this moth species were marked individually and released from a moving train at various distances from the home location,
at which a female of the species was kept in a gauze cage.
From a distance of 4.1 kilometres, 40% of the released males, and from a distance of 11 kilometres 26% returned to the female.“
In 1959 it was Adolf Butenandt again who succeeded in isolating the first pheromone, bombykol,
from 500.000 female silk moths and after 20 years of lab work.
The contribution of small molecules to our health is obviously essential.
But even today not all of them have been identified.
One thing though seems to be sure: Small things matter.