Assignment #2 - The Structure of Serotonin

Assignment #1 - My Favorite Hormone

 

S E R O T O N I N

Introduction

Serotonin is just one of the many important mammalian hormone molecules 

relaying information that control psychological and bodily functions! 

Though serotonin (5-Hydroxytryptamine or 5HT) is widely known as

'the happy neurotransmitter molecule', 60-90% of the total amount of 5HT in

the body (up to 10mg in adults!) exists in the gastrointestinal tract!

That's right--serotonin is also important for signaling digestion and meta-

bolism, as it is involved in the triggering of smooth muscle contraction and

peristalsis in the intestine. (Gaginella and Galligan, p.1-5, 1995)

In this blog, you will learn about the structure, function, and metabolism of

5-Hydroxytryptamine. In addition, the mechanisms of this molecule's 

signaling cascade will be discussed, so buckle your boots for a happy good

time...

Serotonin Synthesis and Structure

Serotonin is a neurotransmitter derived from the amino acid, tryptophan.

In a two step biosynthesis pathway, tryptophan is converted to the 

intermediate, 5-Hydroxytryptophan which is then decarboxylated to give 

rise to 5-Hydroxytryptamine (serotonin). (Lehninger, 2005)

Function

As mentioned in the introduction, serotonin is a neurotransmitter that 

serves to relay information pertaining to both psychological and physical 

body functions. Since a HUGE proportion of brain cells are affected 

either directly or indirectly by serotonin, this potent little tryptophan 

derivative affects our:

• mood
• sexual desire and function
• appetite and digestion
• sleep
• memory and learning
• temperature regulation
• some social behaviours

(Bouchez, 2008, para3)

Trough mental disorders have not been directly liked to any physical 

disorders ofthe brain, serotonin deficiency is widely suspected by 

neuroscientists and psychologists as a major contributing factor to 

described clinical illnesses such as Depression, Anxiety and Obsessive 

Compulsive Disorder (OCD). (Bouchez, 2008, para5) (DSM-IV-TR, 

2000)

Interestingly, the multiple functionality of serotonin is evident from the 

clinical treatment of depression with certain classes of antidepressants. 

This is because their method of action is through the inhibition of 5HT 

re-uptake from the synaptic clefts, which consequences in side effects 

of weight gain in treated patients. Keeping 5HT in mind, we can 

derive the root meaning behind the term 'comfort foods', and a new 

understanding for why we snack constantly during exam week.

Direct Actions

Neutrotransmitter 5-hydroxytryptamine (serotonin or 5HT) acts through receptor

channels that are structurally related to acetylcholine receptors (one of the most

well studied receptors!). Binding of serotonin to its receptor causes an influx of

K+, Na+ and Ca2+ ions, due to the opening of the cation channel. (Lehninger,

2005)

Serotonin acts generally on three types of receptors in the 5HT receptor class

(denoted 5HT1, 5HT2, and 5HT3). Receptors 5HT1 and 5HT2, when bound

to serotonin, act to open ion channels indirectly through the G-protein signal

transduction pathway, and are therefore neurotransmitter receptors termed,

metabotropic. Contrastingly, ionotropic receptors (as is 5HT1) are trans-

membrane ligand gated channels that open directly upon the binding of their

respective neurotransmitter. (Hill et al, 2004)

Serotonin is also produced by some facilitating interneurons. In facilitation,

successive post synaptic potentials (PSPs) increase in response amplitude

with every repeated presynaptic action potential, therefore the threshold for

depolarization becomes more easily obtainable. 5HT acts in facilitation by 

causing an overall increase in the amount of sensory terminal cyclic AMP

(cAMP). cAMP binds to cAMP-dependent protein kinases, turning on their

phosphorylating activities upon K+ channels in the terminal. Phosphorylation

of K+ channels (that let pass through Ca2+ ions) decreases the K+ current

involved in action potential termination (repolarization), therefore depol-

arization is prolonged and the Ca2+ influx is significantly increased.

With high terminal synapse Ca2+ levels, the release of neurotransmitters

results. (Hill et al, 2004).

References

[1] Lehninger, Nelson, David L., and Cox, Michael M. (2005). Principles of 

Biochemistry, 4th Ed. W.H. Freeman and Company: New York, p. 428 and 860

[2] Hill, Richard W., Wyse, Gordan A. and Anderson, Margaret. (2004).

Animal Physiology, 1st Ed. Sinauer Associates, Inc: Sunderland, Mass.

USA. p. 328

[3] Lodish, Harvey et al. (2008). Molecular Cell Biology, 6th Ed. W. H. 

Freeman and Company:New York. p. 1023

[4] Gaginella, Timothy S. (1995). Serotonin in the Intestinal Tract: 

A Synopsis. In Gaginella, T. S. and Galligan, J. J. (1995). Serotonin and 

Gastrointestinal Function, 1st Ed. (p.1-5). CRC Press, Inc: Boca Raton, 

Florida.

[5] Bouchez, Colette. (2008). Serotonin: 9 Questions and Answers. 

Reviewed by Nazario, Brunilda, MD. In WebMD: Depression Health 

Center. Retrieved Sept. 26, 2008, from