#metabolites

To metabolize is to breakdown a chemical to its simpler component forms for cells to use. Psilocybin is a psychedelic compound found in fungi of several genera including Psilocybe, Panaeolus, and Copelandia. Inside the body, it influences the functional molecular mechanisms of several organs, mainly the brain, kidneys, and liver. On its own psilocybin is not as effective. To produce its infamous hallucinogenic effect in the brain, it must be converted to psilocin. Psilocin is the main active molecule, which is derived from the prodrug psilocybin.

There are two ways of getting these metabolites inside the body: oral ingestion (for example, eating the "magic mushrooms") and intravenous injection. When orally ingested, the mushrooms are digested in the usual way. Eventually, the psilocybin in the mushrooms reaches the liver where it is converted to psilocin. An enzyme, alkaline phosphatase, acts on psilocybin such that its phosphate group (PO₄³⁻) is replaced with a hydroxyl group (−OH). Psilocin is further acted upon by diverse enzymes to obtain products which are either excreted through urine or contribute to other functions in hepatocytes (liver cells) as psilocin metabolites.

There is a format to convert chemical equations to sentences. Nevertheless, I firmly believe that one must have the convenience of remembering their organic chemistry without having a stroke. Behold,

psilocin + monoamine oxidase = 4-hydroxyindole-3-acetaldehyde

psilocin + glucuronosyltransferase = psilocin glucoronide (PCG)

psilocin + aldehyde reductase = 4-hydroxytryptophol

psilocin + aldehyde dehydrogenase = 4-hydroxyindole-3-acetic acid (4HIAA)

The fates of each of these products are an elaborate article on their own, and I will be happy to write them should you be interested. Let me know!

Now, we remember that the primary effects due to which human beings consume psilocybin-containing mushrooms are caused by psilocin in the brain. The exact step-by-step mechanism has not yet been outlined; however, general molecular interactions have been found in studies. This psychoactive compound shows an interesting resemblance to serotonin the neurotransmitter. The psilocin binds to 5-HT2A (a molecule in a cell membrane which responds specifically to serotonin i.e., a serotonin receptor) with high affinity, which is believed to be essential for hallucinogenic effect. It also binds to other receptors with varying affinities, although their significance is yet to be understood.

Psilocybin and its metabolized products are completely removed from the body after 24 hours of consumption. The kidneys take pride in detoxifying circulating blood by creating the waste product urine; psilocin consumed can be detected in blood plasma 6-8 hours after consumption. Majority of the psilocin excreted through urine is in the form of psilocin-O-glucoronide. Psilocybin that remains psilocybin is also excreted through urine by the kidneys.

Introducing psilocybin in the body through veins produces effects of similar intensity as the former method. Whereas it remains as an active compound in the blood for a shorter duration. Turton et. al. conducted an fMRI (functional magnetic resonance imaging) study to compare the subjective experience of intravenous psilocybin injection interestingly explains how their participants’ descriptions of their experiences were influenced by the MRI scanner environment and the 1960s, when psychedelics were first introduced to western culture.

bibliography:

Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addiction biology. 2002 Oct;7(4):357-64.

Tylš F, Páleníček T, Horáček J. Psilocybin–summary of knowledge and new perspectives. European Neuropsychopharmacology. 2014 Mar 1;24(3):342-56.

Specific microbiota identified which prevents obesity. Thoughts health innovators?

Obesity and its associated illness type 2 diabetes (T2D) have reached epidemic proportions. Increased food intake and lack of exercise are two main contributing factors, with past research firmly establishing an important role of gut microbiota in metabolic disorders. However, the exact mechanism linking gut microbiota to obesity is yet to be identified. Now, a study from researchers at the…

Metabolite Produced By Gut Bacteria From Pomegranates Reduces IBD

A microbial metabolite, Urolithin A, derived from a compound found in berries and pomegranates, can reduce and protect against inflammatory bowel disease (IBD).

One Step Closer to Finding Out How Wine May Protect Your Neurons

Let there be no misunderstanding: heavy alcohol intake has severe harmful effects. But, for several years, researchers have been finding that moderate wine intake can be beneficial in delaying the onset of cognitive impairments associated with aging and neurodegenerative diseases like Parkinson’s and Alzheimer’s disease.

Dr. Esteban-Fernández from the Institute of Food Science Research in Madrid and her colleagues have been investigating the molecular mechanisms underlying the neuroprotective actions of wine, recently published in Frontiers in Nutrition.

Instead of investigating wine directly, they studied the compounds that are left after the wine has passed through the gut: the so-called wine-derived human gut metabolites. They selected some of these metabolites based on their presence in the urine and feces of people consuming wine on a regular and moderate basis. To explore the neuronal effect of these compounds, they added them to human cells under stress conditions that normally lead to neuronal cell dysfunction and death. These conditions are related to the initial stages of some neurodegenerative disorders.

They found that the metabolites are protecting the cells from dying due to the stress conditions. The most striking result, however, was that the metabolites are active at different points in the cell signaling cascade that is leading to this cell death. The exact composition of the wine metabolites is therefore important in the protective neuronal effect. And this composition depends on your gut microbiota composition, as the intestinal flora breaks down the wine into the different metabolites.

“Neuroprotective Effects of Selected Microbial-Derived Phenolic Metabolites and Aroma Compounds from Wine in Human SH-SY5Y Neuroblastoma Cells and Their Putative Mechanisms of Action” by A. Esteban-Fernández, C. Rendeiro, J. P. E. Spencer, D. Gigorro del Coso, M. D. González de Llano, B. Bartolomé and imageM. V. Moreno-Arribas in Frontiers in Nutrition. Published online March 14 2017 doi:10.3389/fnut.2017.00003

A Blood Test For Autism

An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the Autism spectrum of disorder (ASD), based upon a recent study. The algorithm, developed by researchers at Rensselaer Polytechnic Institute, is the first physiological test for autism and opens the door to earlier diagnosis and potential future development of therapeutics.