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an excitatory neuropeptide chemical


Everything you need to know about orexin and what it does in one simple booklet.


Orexin is an excitatory neuropeptide chemical, and was only recently discovered in 1998. It is an integral part of the endocrine system as it regulates wakefulness, arousal, and appetite - but what is the endocrine system?


The endocrine system, for those of you that don’t know, is what controls the release and production of hormones in your body. It is made up of a collection of different glands, which regulate your metabolism, control your sexual function, reproduction, tissue function (e.g. skin), your growth and development (puberty), your sleep, and your mood, among other things.

“Endocrine” originates from Greek, with ‘endo’ being the Greek word for ‘within’, and ‘crinis’ meaning ‘to secrete’. The glands in the endocrine system choose and remove materials from the bloodstream, and then those materials go through a chemical process and become what we call “hormones”, which are then secreted somewhere within the body.


Endocrine System

Orexin is labelled as an “excitatory neuropeptide chemical”, which means that it is a rapid onset hormone and takes effect if not immediately then very soon after it is released. It is an important hormone as it plays a large role in wakefulness, homeostatic control, and feeding behaviour (there have also been studies that show that high levels of orexin lead to increased happiness, whereas low levels lead to a decrease in mood and energy). A deficiency of orexin results in narcolepsy - a condition where one has a common tendency to fall asleep involuntarily - not just in humans, but in rodents and dogs and even bovines.

These “multi-tasking” neurons also take on reward processes (addiction) , and a deficiency in orexin can cause abnormalities in certain homeostatic processes relating to energy, reward systems within the body, and stress-related behaviour. The link between orexin and the ventral tegmental nucleus (the ventral tegmental area is a group of neurons at the very centre of the brain) is part of what encourages us to take steps and engage in behaviour directed towards a goal.

Orexin also “excites” cholinergic and monoaminergic neurons in the brainstem and hypothalamus which allows us to stay awake for a single long period of time. The neurons have reciprocal links to the hypothalamic nuclei, and are incredibly responsive to outlying metabolic cues, which regulates feeding and shows there’s a strong link between energy homeostasis and vigilance states.


What Does orexin do?

Orexin is produced when we are suffering from sleep deprivation (not having enough sleep, whether that be involuntary or voluntary), which is why we are able to stay awake despite pulling an all-nighter - orexin helps to sustain alertness. It is also released when we have a low metabolism - whether from low blood sugar levels, lack of exercise etc. - which increases our appetite in order for our bodies to have the energy we need to complete our daily activities. Orexin is also linked to sexual behaviour in males - however, the extent of this research has been done on rats and it’s yet to be determined whether or not it has an effect on humans.


when is orexin produced?

Orexin A’s chemical structure is C152H243N47O44S4 - 152 carbon atoms, 243 hydrogen atoms, 47 nitrogen atoms, 44 oxygen atoms, and 4 sulfur atoms.


Orexin B’s chemical structure is C123H212N44O35S - 123 carbon atoms, 212 hydrogen atoms, 44 nitrogen atoms, 35 oxygen atoms, and a singular sulfur atom.

There are two types of orexin - A and B. The difference between them is in the chemical structure: orexin A is 33 amino acid residues long, and has two intrachain SS-bonds, whereas orexin B is only 28 amino acid residues long and is linear. Scientists believe orexin A may be more biologically important than B, but have yet to find convincing proof.


Orexin is only produced by a small cluster of glands in the hypothalamus - the part of the forebrain that lies below the thalamus and co-ordinates our autonomic nervous systems and homeostatic systems (body temperature, hunger, thirst etc.) -, a number ranging from 100 000 - 200 000 neurons releasing this hormone into the brain.



glands and types of orexin

Orexin A and B both bind to a G protein-coupled receptor of which there are two variants - OX1 and OX2. OX1 selectively binds to orexin A, and is encoded with the HCRTR1 gene and shares 64% of it’s DNA with OX2. OX2 binds to both orexin A and B and is encoded with the HCRTR2 gene. Both are involved in regulating feeding behaviour.


And that is a basic overview of what orexin is, how it affects you and why we need it. On the following page, there is a comic showing what happens when you are suffering from a deficiency of orexin, and a diagram of orexin in the brain - what a normal spread out of orexin looks like, and what a narcoleptic's spread of orexin looks like.

orexin receptors