Myristoylation, HID-1, nutmeg, and colon cancer

I recently came across a possible encoded message that was about an "apo-HID." "Apo" in biology means a molecule that is missing an important subpart such that it no longer does what it is usually supposed to do.

There is an enzyme called "HID-1." It looks like an "apo" version of it exists when myristoylation fails to occur:

Finally, we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus.

"HID-1 is a peripheral membrane protein primarily associated with the medial- and trans- Golgi apparatus," 2011, online at https://pmc.ncbi.nlm.nih.gov/articles/PMC4875289/

In eukaryotes, most proteins must undergo alternative splicing and extensive modifications, such as protein glycosylation, phosphorylation, or lipidation, after synthesis to reach their active and functional forms. Indeed, attachment of lipid groups is vital for proteins to achieve their final native structure and to allow intracellular transport for them to reach the appropriate cellular localization. Protein lipidation can be divided into four major types: N-myristoylation, S-palmitoylation, prenylation, and glycosylphosphatidylinositol anchor conjugation.

N-myristoylation is a ubiquitous protein lipid modification that occurs cotranslationally in eukaryotes and involves attachment of myristic acid to the N-terminal glycine (Gly) of a wide range of substrate proteins.

"Protein N-myristoylation: functions and mechanisms in control of innate immunity," 2021, online at https://pmc.ncbi.nlm.nih.gov/articles/PMC7966921/

What is myristic acid? It's a saturated fatty acid. (See https://webbook.nist.gov/cgi/cbook.cgi?ID=C544638.) It's found in butter, coconut oil, palm kernel oil, and especially in nutmeg oil:

Nutmeg butter has 75% trimyristin, the triglyceride of myristic acid and a source from which it can be synthesised. Besides nutmeg, myristic acid is found in palm kernel oil, coconut oil, butterfat, 8–14% of bovine milk, and 8.6% of breast milk as well as being a minor component of many other animal fats. It is found in spermaceti, the crystallized fraction of oil from the sperm whale. It is also found in the rhizomes of the Iris, including Orris root.

Downloaded from https://en.wikipedia.org/wiki/Myristic_acid on October 8, 2024.

Myristic acid appears to have an anti-tumor effect in the human body. 

Myristic acid has been widely confirmed to have strong antitumour effects, which induce apoptosis of many kinds of tumor cell[s], such as breast cancer cells, prostate cancer cells, stomach cancer cells, liver cells, and other.

"Antimicrobial potential of myristic acid against Listeria monocytogenes in milk," 2019, https://www.nature.com/articles/s41429-019-0152-5. 

Nutmeg itself in mice has been demonstrated to help prevent the formation of colon cancer tumors. See "Modulation of Colon Cancer by Nutmeg," 2015, https://pmc.ncbi.nlm.nih.gov/articles/PMC6334305/.

HID-1 is more highly expressed in cancers generally. See https://www.proteinatlas.org/ENSG00000167861-HID1/pathology. Perhaps I found a valid message pointing to a need to increase the N-myristoylation of HID-1 to help prevent cancer tumors. It would be interesting to look at whether the myristic acid content of milk has been decreasing at the same time as there has been an increase in colon cancers in young adults.

[Update: Because milk has myristic acid and milk/dairy consumption is very high globally, I think there is something even more complicated going on than just the presence or absence of myristic acid. The process of N-myristoylation apparently uses the compound CoA-HS:

Downloaded from https://alchetron.com/Myristoylation on October 8, 2024.

What if our dairy processing nowadays is making it so there is either too much or too little CoA-HS and so affecting N-myristoylation? It would be interesting to see what other small molecules nutmeg contains in conjunction with HID-1 and myristic acid. Is there a lithium version of this myristoylation ingredient (e.g., CoA-LiS) that causes myristoylation to happen differently? Is there a -1 sulfur anion that messes with the process? Or, what would happen if there were two-proton hydrogen in place of the usual H+ ion? How I wish I had better technology to see what is in my food!]