Sickle cell anemia and valine biochemistry

I know it’s not tis that season, but would you be my Valine-tine? Today in #20DaysOfAminoAcids, another protein letter to fall in love with! And with 3 times the carbon as Ala’s chain, there’s 3 times as much to love! Unless this hydrophobe winds up on the surface of proteins, where it can cause diseases like sickle cell anemia… But in addition to branching off on that segue, I’ll discuss branched chain amino acids (BCAAs) and why it’s “essential” to read this post… erm, I mean it’s essential to eat valine… blog form (text old, video new): http://bit.ly/valinevalue It’s Day 3 of #20DaysOfAminoAcids - the bumbling biochemist’s version of an advent calendar. Amino acids are the building blocks of proteins. There are 20 (common) ones, each with a generic backbone 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. More on amino acids in general here http://bit.ly/aminoacidstoproteins  But today the bumbling biochemist puts in a valiant effort to tell you about valine and convince why it’s of great value! Day 1 we looked at glycine (Gly, G) which just had a teeny-weeny H (hydrogen) as its R group. Then yesterday we stepped up in size with the next-smallest, Alanine (Ala, A) which had a methyl (CH₃) group for an R. Add 2 more methyl (CH₃) groups branching off the end of yesterday’s amino acid alanine (Ala, A) & you get VALINE (Val, V), BUT it’s not quite that simple. In fact, unlike Ala, our bodies can’t even make Val at all - it’s an “essential” amino acid meaning we need to get it from food. (don’t confuse essential in the dietary sense for essential in the biological sense - when we say amino acids like alanine are “nonessential” we aren’t saying we don’t need them, we’re just saying that we don’t need to get them “pre-made” in our food because our bodies can make (synthesize) them from other molecules we eat and/or break down. (we’ll talk more about this later in the post) It’s a lucky coincidence that the side chain (aka R group - the “unique part” of an amino acid) of V is shaped like a V! The name actually comes from the related valeric acid, whose name comes from the valerian plant it’s found in. Speaking of finding it - let’s start by talking about how it was discovered - a half-century-long saga of how its structure was uncovered! This holiday classic to be (if I get my say…) begins back in 1856 with a chemist named von Gorup-Besanez who wanted a glance at the chemicals in glands. He minced up some pancreas and extracted stuff out of it. He found the amino acids leucine and tyrosine (the ones he was looking/testing for) but he also found something that behaved a lot like leucine but was less soluble in boiling alcohol. He figured out the empirical formula C₅H₁₁NO₂ - so he knew the thing he’d found was made up of carbon, hydrogen, nitrogen, & oxygen - and he even knew how many atoms each there were compared to one another, but not how those atoms connected. https://doi.org/10.1021/cr60033a001 In the 80s (the 1880s that is) other groups found it in albumin and sprouts of Lupinus luteus and Vicia stativa. So it was found in a variety of places, but those scientists didn’t try to find out the linkages. Other scientists did. But they all had a hard time figuring out how the atoms were hooked up. Was it 3C in a row? 1 and 2? Was the nitrogen stuck to the end of 1 long chain? So basically most of the first half a year of research on what we now know as valine was different chemists synthesizing different possible linkages and then comparing how those compounds behaved compared to the real deal Gorup-Besanez had found in the pancreas. But they were still having problems because their synthesis products contained a mix of stereoisomers. Yesterday we saw how alanine, unlike glycine is chiral - meaning it has non-superimposable mirror images (like your right & left hands). Glycine is not chiral because it has 2 of the same thing sticking off its central carbon (Cα) and you need 4 different things to be chiral. But all the other amino acids, including valine, have those 4 different things, so they are chiral. Finished in comments