Basic Amino Acids MCAT + Histidine Tautomerization | MCAT

[@medcatmcat]

Polar and nonpolar amino acids coming tomorrow and the day after!

[@codyko7178]

Isn't histidine aromatic as well?

[@medcatmcat]

@@codyko7178 Histidine is aromatic; that is a really good point. However, because its function as a base is so important, it's main "identity" is as a base rather than as an aromatic amino acid-so much so that most MCAT content books omit it from the aromatic amino acid lists.

[@forgentlesoul4054]

I still am quite confused as to why histidine (pKa = 6) isn't considered weakly acidic but basic? and you clearly indicated that arginine and lysine having overall charge of +1 from the diagram 8:20 but you call them polar (not charged)? Great video :) I see you uploaded them 3 yrs ago but I still find it very useful thx

[@medcatmcat]

Hello! I'm glad you find them useful. The classification of histidine is frustrating. It is a good reminder of another high-yield concept, though, which is the definition of pKa: the pH at which an equal amount of protonated and nonprotonated species will exist of that particular molecule. If we solve the Henderson-Hasselbach equation and give [A-] and [HA] the same value, we see that pKa must equal pH. This reminds us of an even more fundamental concept-not easy, but fundamental-which is that when we talk about histidine, singular, we actually mean an unfathomable number of histidine molecules. For simplicity, we say histidine is neutral at physiologic pH, 7.4, because the pH > pKa, and the proton that histidine sometimes likes to have is taken by the solution. However, because there are a ton of histidine molecules, some of them are going to be protonated, and in fact, because the pKa is reasonably close to the pH, a nonsignificant number of them will be found protonated in the body. What's more is that the entirety of the body is not homogenous, and some local enzymes and environments in the body will favor one form over another-a little bit of hand-waving here since this is above my pay grade. Let me know if that makes sense.

[@jarrettleto]

Histidine is a tough one, and I wanted to clarify something you said. You said "Histidine is going to be neutral at any pH above 6", but I don't think that's completely correct. I'm honestly still trying to wrap my head around this because a question in AAMC material said histidine was positive at pH of 8 (which really doesn't make sense to me but ok), so I think its important to point out to people watching. Side chain pka of around 6 means at pH of 6, then 50% of histidine's R group is protonated (positive) and half is deprotonated (neutral) so it would carry a net charge of ~0.5+ of pH 6. I believe its isoelectric point is right around 7.5 or 7.4 (physiological pH) so that is the point where it is truly neutral. Even a pH of 7 would give you a charge of ~+0.1 or +0.09 on histidine, technically.

[@medcatmcat]

An individual molecule of histidine does not carry a partial positive or negative charge-it either has the proton or it doesn't. What you're probably thinking of is the total concentration of a bunch of histidine molecules in solution. The Henderson-Hasselbach equation applies to concentration of species, not an individual molecule. In other words, what I am saying is that unless the question specifies otherwise, the histidine you randomly select from the solution will be neutral as pH > pKa. What AAMC question are you referring to?