MSG myth debunking and glutamate biochemistry

Glutamate, ionic “bonds,” salts, chemophobia, acidic amino acids, transamination, MSG myth, etc…. MSG? Fine by me! It’s just a salt of glutamate, so why does everyone gotta hate? From giving food its rich umami taste, to helping your cells safely remove nitrogenous waste, there’s a lot to love about this protein letter, so today I want to help you get to know it better! It’s more “popular” for its role as a brain messenger, but for those functions to brain experts I shall defer - instead, I hope you won’t become irate if I focus on some of the other (just as, if not more so) vital functions of glutamate (Glu, E)!

It’s Day 19 of #20DaysOfAminoAcids - the bumbling biochemist’s version of an advent calendar. Amino acids are the building blocks of proteins. There are 20 (common) genetically-specified ones, each with a generic backbone with to allow for linking up through peptide bonds to form chains (polypeptides) that fold up into functional proteins, as well as unique side chains (aka “R groups” that stick off like charms from a charm bracelet). Each day I’m going to bring you the story of one of these “charms” - what we know about it and how we know about it, where it comes from, where it goes, and outstanding questions nobody knows.

Those generic parts are attached to a central “alpha carbon” (Ca), which is also attached to one of 20 unique side chains (“R groups”) which have different properties (big, small, hydrophilic (water-loving), hydrophobic (water-avoided), etc.) & proteins have different combos of them, so the proteins have different properties. And we can get a better appreciation and understanding of proteins if we look at those letters. So, today let’s look at Glutamate (Glu, E)!

Glutamate is best known for its role a a neurotransmitter - a brain signaling molecule that nerve cells (neurons) use to communicate to other neurons. Want to send a message? - ship out some glutamate into the space between the cells (synapse) and that glutamate will bind to special receptors on the other cell, channels will open, and ions will rush in, leading to a change in charge that makes other channels open easier, sets off signaling cascades, etc. It’s cool stuff - but so many people find it cool that its role as an excitatory neurotransmitter tends to get all the spotlight. So today I want to tell you about some of the other aspects of glutamate that are just as - if not even more - important, yet are way further down the search results if you Google it.

Glutamate isn’t only important for neurons - it’s important for ALL our cells - really important - because it’s one of the key ways we can recycle amino acids while safely handling the nitrogen part. I’m going to tell you about this key role in “transdeamination” in a minute, but first I want to address something that might show up along with the brain stuff in your Google search - I’m talking about the myth that MSG added to food causes all sorts of symptoms like headaches, racing heart, tingling limbs, etc.

MSG stands for MonoSodium Glutamate and it’s just the sodium salt of glutamate. It gets added to food sometimes because glutamate is responsible for that rich “5th flavor,” umami. “Salt” is just another name we give to a neutral ionic compound - ions, by definition, are charged, thanks to their imbalance of protons & electrons (more below). So in order to get a salt you have to have a positive thing(s) (cation) and a negative thing (anion) - but you can mix and match. Stick a sodium ion (Na⁺) with a chloride ion (Cl⁻) and you get NaCl, or as you might know it better, table salt. If, instead of a chloride ion you stick the sodium with a glutamate anion, you get monosodium glutamate (MSG). Add in some disputed science and xenophobia and you get the myth that MSG causes a variety of strange symptoms.

I’m not just going to tell you it’s not true - it isn’t, but I want you to really understand what’s going on - especially since part of the reason the whole MSG myth has flourished is because of misunderstanding and chemophobia fueled by commercial opportunism (i.e. if it has a weird chemical name it must be dangerous so we’ll not use weird names on our labels…). Remember, dihydrogen monoxide is just a fancy name for water (and, for the lab nerds out there, DTT by any other name would still smell just as eggy) so don’t let companies profit off chemophobia!

finished in comments

[thebumblingbiochemist]

Please note that I am in no way judging people for being misled - I recognize that chemistry knowledge is an immense privilege that not everyone has a chance to gain which is why I want to help share it with others. And I’m also not saying that all chemicals are good in all contexts - I just think it’s important to not immediately equate “chemical” with “bad”. Thank you for coming to my TED talk…Steps off soapbox to continue telling you about MSG - or, let’s spell it out why don’t we - MonoSodium Glutamate

My first task - convince you that chemistry is really really really cool! It’s like a magical molecular dance underlying everything, so let me introduce you to some of the key players. Biochemical molecules are a bit like LEGOs - from carbohydrates (simple sugars like glucose to more complex storage forms like starches, glycogen etc.) to lipids (fats, cell membrane pieces, etc.) to proteins and even mixtures of them - glycoprotein anyone? - they’re all made up of the same kinds of pieces - atoms. Atoms are the basic units of elements - think black LEGOs vs. blue LEGOs except that, instead of colors, the difference between elements (e.g. carbon (C) vs nitrogen (N)) is the # of protons they have.

Protons are little positively charged things & they’re one of 3 key subatomic particles - they hang out with neutral neutrons in a dense central atomic nucleus and then negatively-charged electrons (which have an equal but opposite charge despite being itty-bitty-er) whizz around them in an electron cloud. You can never know exactly where an electron will be - but there are places they most like to hang out, which we call “orbitals.”

At the physical chemistry (p-chem) level, it’s not really like this, but it can be really helpful to think of electron orbitals as “shells” or onion layers. The periodic table is like a “menu” of all the known elements - as you look down a column (these columns are frequently called groups or families), you add a layer but keep the same number of electrons in the outermost shell in the element’s neutral form - and, conveniently, that # is the same as the column # (i.e. carbon is in the 4th column (of the main groups of the table) & it has 4 valence electrons in its neutral form whereas nitrogen, in the 5th column has 5, & oxygen, in the 6th column has 6). These outermost electrons are called valence electrons - they’re the most energetic and, being furthest away from the positive pull of the nucleus, they’re “least loyal” to the atom they come from, and more liable to interact with electrons of neighboring atoms and even leave altogether.

Why would they want to do that? For reasons outside the scope of this post, atoms are usually most stable (and thus happiest) if they have a full “outer shell” like the elements in the last column (the Noble gases) do - for most of the elements we commonly deal with in biochemistry, this means having an octet - 8 electrons in the outer shell (an exception is hydrogen, which only wants 2 because its outer shell is an inner shell for everyone else (except helium). Hydrogen only has a single proton, so you can’t expect it to reign in a ton of electrons! In fact, H often has trouble controlling the single one and, when it loses it (like if it leaves a covalent bond without it) you’re left which just a proton (and a neutron) which is why we often refer to H⁺ as a proton. Note: we call proton donators acids and proton acceptors bases, as will come into play later.

As you can see by the little ⁺ in our proton example, if a neutral molecule loses an electron, the # of protons > # electrons, so it becomes positively-charged (cationic) and if a neutral molecule gains an electron, # of protons < # of neutrons, so it becomes negatively-charged (anionic). “Ionic” just refers to a charged thing and things usually don’t really want to be charged. So there’s this kind of compromise atoms have to make with regards to getting that full outer shell vs becoming charged, and what decision they make has to do with things like how close they are to full and how well they can handle the charge (for example, communal electron sharing through “resonance” aka “electron delocalization) as occurs in the carboxylate ions we’ll look at, helps)

If they do decide to go charged, they commonly also get “help” from other molecules - since opposite charges attract, cations are attracted to anions & vice versa - so even when Na (which has one electron it doesn’t want in a shell all to itself) gives up an electron to Cl (which just needs one to complete its shell) to give you Na⁺ & Cl⁻, those ions hang out together through an “ionic bond” which is really just a strong attraction - unlike covalent bonds (like those linking together amino acids) which involve electron sharing (i.e. orbitals unite!)

Glutamic acid is the neutral form of Glu and, like aspartic acid (Asp, D), it’s capped off by a carboxylic acid group -(C=O)-OH (the difference between Glu & Asp is that Glu has a longer linker (2 methylene (-CH₂) groups versus one). So Glu & Asp have a second carboxyl group (the first being in the generic backbone part which gets lost during peptide bond formation (amino acid letter linking). As the name “acid” implies, they’re willing to give up a proton - sometimes…

Willingness to give up a proton (acid strength) is characterized by the pKa, which tells you the pH at which half of the thing will be protonated - above the pKa (more basic/alkaline conditions), there are fewer protons around, so the thing is more likely to deprotonate whereas below the pKa (more acidic conditions) there are more protons around, so it’s likely to be protonated. Protonation is reversible so the deprotonated form can “change its mind” - act as a base and take a proton - thus we can call the deprotonated form of an acid its “conjugate base” and, by comparing the pKa to the pH you can predict which form will dominate.