<article_title>Amino_acid</article_title>
<edit_user>96.54.32.44</edit_user>
<edit_time>Friday, February 25, 2011 1:38:26 AM CET</edit_time>
<edit_comment>/* Zwitterions */ expanded the original zwitterion subsection and set up a separate subsection to describe the isoelectric point</edit_comment>
<edit_text>Zwitterions
The amine and carboxylic acid functional groups found in amino acids allow <strong><strike>it</strike></strong><strong>them</strong> to have amphiprotic properties.&lt;ref name=&quot;Creighton&quot; /&gt; Carboxylic acid groups (-CO&lt;sub&gt;2&lt;/sub&gt;H) can be deprotonated to become negative carboxylates (-CO&lt;sub&gt;2&lt;/sub&gt;&lt;sup&gt;-&lt;/sup&gt; ), and α-amino groups (NH&lt;sub&gt;2&lt;/sub&gt;-) can be protonated to become positive α-ammonium groups (&lt;sup&gt;+&lt;/sup&gt;NH&lt;sub&gt;3&lt;/sub&gt;-). At pH values greater than the pKa of the carboxylic acid group (mean for the 20 common amino acids is about 2.2, see the table of amino acid structures above), the negative carboxylate ion predominates. At pH values lower than the pKa of the α-ammonium group (mean for the 20 common α-amino acids is about 9.4) the nitrogen is predominantly protonated as a positively charged α-ammonium group. Thus at pH between 2.2 and 9.4, the predominant form adopted by α-amino acids contains a negative carboxylate and a positive α-ammonium group as shown in structure (2) on the right, so has net zero charge. This molecular state is known as a zwitterion, which comes from the German word Zwitter meaning &quot;hermaphrodite&quot; or &quot;hybrid&quot;.&lt;ref&gt;&lt;/ref&gt; Below pH 2.2, the predominant form will have a neutral carboxylic acid group and a positive α-ammonium ion (net charge +1), and above pH 9.4, a negative carboxylate and neutral α-amino group (net charge -1). The fully neutral form (structure (1) on the right) is a very minor species in aqueous solution throughout the pH range (less than 1 part in 10^7). Amino acids also exist as zwitterions in the solid phase, and crystallize with salt-like properties unlike typical organic acids or amines.</edit_text>
<turn_user>96.54.32.44<turn_user>
<turn_time>Friday, February 25, 2011 1:35:09 AM CET</turn_time>
<turn_topicname>Overemphasis of the neutral form</turn_topicname>
<turn_topictext>Practically all the figures in this article show neutral amino and carboxylic acid on the same molecule. Zwitterions are mentioned, but almost as an aside. In reality, amino acids in neutral aqueous solution and in crystalline solid state are zwitterions. The ratio of zwitterion to neutral at pH 7 is about 10^7 to one. At more acidic pH, the carboxylate becomes protonated, but so is the amino group. At high pH the amino group is deprotonated, but so is the carboxylate. Nowhere on the pH scale are there significant concentrations of the neutral carboxylic acid and neutral amino group on the same molecule.96.54.32.44 (talk) 06:52, 16 February 2011 (UTC) It all comes down to convention. Amino acids are very widely depicted in the scientific literature in their neutral forms, and Wikipedia's role is to report on what others write. We shouldn't aim to defy convention in order to be technically more accurate. We are writing about "amino acids", after all, not "ammonium carboxylates". If anything needs to be changed, I would suggest adding further discussion of their true chemical structure, more than the current degree ("almost as an aside"). 148.177.1.210 (talk) 20:33, 16 February 2011 (UTC)So Wikipedia is an encyclopedia that subscribes to inaccuracy?96.54.32.44 (talk) 19:05, 17 February 2011 (UTC)If reliable sources describe the world inaccurately, then yes, so do we. Wikipedia:Verifiability, not truth. 148.177.1.210 (talk) 19:13, 17 February 2011 (UTC)Interesting discussion. The fully uncharged form can exist in nonpolar solvents (e.g. cyclohexane), hence the picture is not an error, generally speaking. Biophys (talk) 20:55, 17 February 2011 (UTC)The zwitterion form is depicted in many textbooks, e.g. Fersht, Structure and Mechanism in Protein Science, 3rd Ed.(1999) pp.2-3. The biochemical standard state is described as aqueous solution, pH 7, 1 atm pressure 298 K (Tinoco, Sauer and Wang, Physical Chemistry, Principles and and Application in Biological Sciences, 3rd Ed (1995) p.139. If we are to consider amino acids in terms of biochemistry, that should be the defining state. Moreover, amino acids are barely soluble in non polar solvents precisely because of the huge thermodynamic penalty of either desolvating the zwitterion or converting to the neutral form. 96.54.32.44 (talk) 00:33, 18 February 2011 (UTC)Of course it would be better to use a good picture with zwitterionic form if we have it.Biophys (talk) 04:32, 18 February 2011 (UTC)There are already a couple of images showing the zwitterion. The problem is that they appear as an aside, while the virtually non-existent neutral form is emphasized in 24images, including the main table of structures. Ironically, the structures show aspartate and glutamate with deprotonated side-chain carboxylates despite the fact that the pKa values dictate that alpha-carboxylic acid will deprotonate before the side chain does. There are indeed plenty of sources with all the amino acids in zwitterion form, the only issue being copyright of images. Most of the amino acids were discovered prior to the formulation of Brønsted-Lowry description of acid/base behaviour, hence older texts adhered to the older convention. 96.54.32.44 (talk) 19:05, 19 February 2011 (UTC) I asked WP:Chemicals for input, since this is a fundamental question to presenting the diagrams of these types of structures in many articles. DMacks (talk) 19:19, 19 February 2011 (UTC) For what its worth, I checked three textbooks that I have; one biology, one biochemistry, and one organic chemistry (all from the mid 1990s). They all depict amino acids as the neutral compounds. Looking at http://www.britannica.com/EBchecked/topic/20691/amino-acid I see the same. So the suggestion that this is the standard convention seems accurate. Because the protonation state of each amino group and each carboxylic acid group is going to vary depending on conditions (solvent, pH, etc.), defaulting to all neutral representations makes sense, despite the fact that zwitterions and various other charged states are going to be the predominant forms under typical conditions. -- Ed (Edgar181) 21:05, 19 February 2011 (UTC) I agree with you all that the zwitterion is an acceptable form in physiological PH (Conributor 96.54.32.44). What form you Wiki guys want to use is up to you all. I agree the neutral form cannot exist at physiological PHs. This fact does not prevent the neutral form's existence. The molecule could exist, due to equilibrium, at low, possibly undetectable, concentrations. If people here come to an agreement on what ionized form to show, can someone do the following? I only wish the contradicting views in the main Amino Acid page be corrected. Please, someone with the authority to edit the Amino acid page edit the All Caps sentence in the first paragraph. The sentence looks bad. I assume the author of all-caps sentence meant amino acids cannot exist at physiological PHs in a neutral form. An outright declaration of contradicting views on a main Wikipedia page is confusing to the general public.69.229.121.10 (talk) 05:21, 20 February 2011 (UTC)The only all-caps sentence I see in recent article history was inserted and then removed 6 seconds later a few hours ago. DMacks (talk) 09:44, 20 February 2011 (UTC) I don't necessarily suggest that all the figures be changed, but rather am concerned that the zwitterion form, which is the predominant form under biochemical conditions is barely mentioned, and one might expect the subject of amino acids to be of interests to biochemists or individuals trying to learn something of biochemistry. The paragraph labelled Zwitterion digresses into discussing isoelectric points, saying the following: "The amine and carboxylic acid functional groups found in amino acids allow it to have amphiprotic properties.[9]" No problem. "At a certain pH, known as the isoelectric point, an amino acid has no overall charge since the number of protonated ammonia groups (positive charges) and deprotonated carboxylate groups (negative charges) are equal.[18] The amino acids all have different isoelectric points. The ions produced at the isoelectric point have both positive and negative charges and are known as a zwitterion, which comes from the German word Zwitter meaning "hermaphrodite" or "hybrid".[19]" One could be misled to understand that the zwitterion only occurs at the isoelectric point, whereas it is actually present as the major form from ~pH 2.2 (mean alpha-carboxylic acid pKa) through to ~pH 9.4 (mean pKa of the alpha-ammonium ion). At pH &lt; 2.2, the positive ion predominates, and at pH &gt; 9.4 the negative ion predominates. "Amino acids can exist as zwitterions in solids and in polar solutions such as water, but not in the gas phase.[20] Zwitterions have minimal solubility at their isolectric point" True enough, except the "can" implies other possibilities without specifying what they are. Given all the information presented in the structure figures, one might think that the zwitterion is a special case rather than the major form present. "and an amino acid can be isolated by precipitating it from water by adjusting the pH to its particular isoelectric point." which is only really true for the hydrophobic amino acids; more polar amino acids reach a minimum point in their pH/solubility curve, but are still relatively quite soluble. What I suggest is a rewrite, dividing into two paragraphs: Zwitterions The α-amino and carboxylic acid functional groups found in amino acids allow them to have amphiprotic properties.[9] Carboxylic acid groups can be deprotonated to become negative carboxylates, and α-amino groups can be protonated to become positive α-ammonium groups. At pH values greater than the pKa of the carboxylic acid group (mean for the 20 common amino acids is about 2.2, see the table of amino acid structures above), the negative carboxylate ion predominates. At pH values lower than the pKa of the α-ammonium group (mean for the 20 common α-amino acids is about 9.4) the nitrogen is predominantly protonated as a positively charged α-ammonium group. Thus at pH between 2.2 and 9.4, the predominant form adopted by α-amino acids contains a negative carboxylate and a positive α-ammonium group as shown in structure (2) on the right, so is net zero charge. This molecular state is known as a zwitterion, which comes from the German word Zwitter meaning "hermaphrodite" or "hybrid".[19] Below pH 2.2, the predominant form will have a neutral carboxylic acid group and a positive α-ammonium ion (net charge +1), and above pH 9.4, a negative carboxylate and neutral α-amino group (net charge -1). The fully neutral form (structure (1) on the right) is a very minor species in aqueous solution throughout the pH range (less than 1 part in 10^7). Amino acids also exist as zwitterions in the solid phase, and crystallize with salt-like properties unlike typical organic acids or amines. Isoelectric point At pH values between the two pKa values, the zwitterion predominates, but coexists in dynamic equilibrium with small amounts of net negative and net positive ions. At the exact midpoint between the two pKa values, the trace amount of net negative and trace of net positive ions exactly balance, so that average net charge of all forms present is zero.[18] This pH is known as the isoelectric point pI, so pI = (pKa1 + pKa2) / 2. The individual amino acids all have slightly different pKa values, so have different isoelectric points. Amino acids have zero mobility in electrophoresis at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids. Zwitterions have minimum solubility at their isolectric point and some amino acids (particularly with non-polar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point. "but not in the gas phase.[20]" Reference cited does not really say this. It's based on theoretical calculations for certain metal complexes of glycine, so "gas phase" exists as a computational state rather than one that can be experimentally achieved.\ 96.54.32.44 (talk) 08:37, 20 February 2011 (UTC) I'm sorry, I don't have any of my basic biochemistry textbooks on hand to cite chapter and verse, but I'm sure you will find this discussed in Metzler, or Creighton, or Lehninger, particularly the old Blue Lehninger (1975) rather than the newer Ouija board versions of "Lehninger". 96.54.32.44 (talk) 08:44, 20 February 2011 (UTC) To me, that looks like an excellent revision. Many thanks, Walkerma (talk) 03:41, 21 February 2011 (UTC)Sounds like improvement. "Gas phase" may refer to something observed by Mass spectrometry. Do not forget that isolectric points also depend on the presence of side-chain charge (Arg, Lys, His, Asp, Glu, etc.). Biophys (talk) 20:38, 21 February 2011 (UTC)Reference (20) discusses transition metal complexes of amino acids, where the amino rather than the ammonium group acts as the ligand, thus metal complex formation significantly alters the normal pKas of the free amino acid. It may be interesting chemistry, but is straying far away from typical biochemical behaviour of the amino acids. Mass spec, as far as I know, always deals in ions so that they can be accelerated and deflected by electric and magnetic fields and detected by deposition of charge at the detecting anode. In conventional mass spec, amino acids are usually derivatized to enhance their volatility. Gas phase infra-red spectroscopy should be able to tell the difference between zwitterion and neutral molecule, but I'm not aware of any literature on the topic.I did not go into the isoelectric points of amino acids with charged side chains in order to keep things straightforward, but if you like they could be included, as in following paragraph: Isoelectric point At pH values between the two pKa values, the zwitterion predominates, but coexists in dynamic equilibrium with small amounts of net negative and net positive ions. At the exact midpoint between the two pKa values, the trace amount of net negative and trace of net positive ions exactly balance, so that average net charge of all forms present is zero.[18] This pH is known as the isoelectric point pI, so pI = ½(pKa1 + pKa2). The individual amino acids all have slightly different pKa values, so have different isoelectric points. For amino acids with charged side chains, the pKa of the side chain is involved. Thus for Asp, Glu with negative side chains, pI = ½(pKa1 + pKaR), where pKaR is the side chain pKa. Cysteine also has potentially negative side chain with pKaR = 8.14, so pI should be calculated as for Asp and Glu, even though the side chain is not significantly charged at neutral pH. For His, Lys and Arg with positive side chains, pI = ½(pKaR + pKa2). Amino acids have zero mobility in electrophoresis at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids. Zwitterions have minimum solubility at their isolectric point and some amino acids (particularly with non-polar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point. Then of course, I could add an explanation of why the particular pKas are chosen for calculation of pI and so on. I personally prefer the simpler version but either would do. 96.54.32.44 (talk) 22:53, 21 February 2011 (UTC)I think you should simply go ahead and make the changes you prefer. If others disagree on details, they would fix your text a little.Biophys (talk) 17:49, 22 February 2011 (UTC)OK, I have put the two paragraphs into the main page. I dropped the old ref 20: the article simply did not support the statement in the original text. 96.54.32.44 (talk) 01:35, 25 February 2011 (UTC)</turn_topictext>
<turn_text>OK, I have put the two paragraphs into the main page. I dropped the old ref 20: the article simply did not support the statement in the original text. 96.54.32.44 (</turn_text>