# Amino acids

> Chemistry · CIE A-Level
> Source: https://www.owlsprep.com/study/cie-9701-u25-amino-acids/

This sub-topic covers the core structure, acid-base properties, and key chemical behaviour of α-amino acids, the monomer building blocks of proteins. You will learn how pH affects their ionic form and reactivity.

**Prerequisites:** [Brønsted-Lowry acid-base theory](https://www.owlsprep.com/study/cie-9701-u08-acids-and-bases/); [Functional group chemistry of amines and carboxylic acids](https://www.owlsprep.com/study/cie-9701-u18-carboxylic-acids-and-derivatives/)

## Learning objectives

- Recall the general structure of an α-amino acid
- Describe amphoteric behaviour of amino acids
- Explain zwitterion formation as a function of pH
- Distinguish between essential and non-essential amino acids
- Predict the overall charge of an amino acid at any given pH

## General Structure of α-Amino Acids

All amino acids that form naturally occurring proteins are α-amino acids. This means the amino group ($-NH_2$) and carboxylic acid group ($-COOH$) are both bonded to the same (α) carbon atom, along with a hydrogen atom and a variable side chain called the R-group.

**α-amino acid** — A carboxylic acid with an amino group bonded to the α-carbon (the carbon adjacent to the carboxyl group)

*Notation:* NH₂CH(R)COOH

*Example:* Glycine (R = H), alanine (R = CH₃)

$$NH_2-CH(R)-COOH$$

**Worked example:** Draw the condensed and general structure of alanine, which has an R-group of $-CH_3$.

1. Recall that the central α-carbon of an α-amino acid has four substituents: $-NH_2$, $-COOH$, $-H$, and the R-group.
2. Substitute the R-group $R = -CH_3$ into the general structure to get the condensed formula:

   $$H_2N-CH(CH_3)-COOH$$

## Zwitterions and Amphoteric Behaviour

Amino acids contain both an acidic carboxyl group and a basic amino group, so they are amphoteric, meaning they can react as both acids and bases. In neutral solution, an intramolecular proton transfer occurs from the carboxyl group to the amino group, forming a doubly charged ion called a zwitterion.

**Zwitterion** — A neutral molecule with equal numbers of positive and negative charges, giving an overall net charge of zero

> **Key Property**
>
> Amino acids are least soluble at their isoelectric point because zwitterions have no net charge to interact with water molecules, so they often precipitate out of solution.

**Worked example:** Show the formation of a zwitterion from glycine (R = H).

1. Start with the un-ionised structure of glycine:

   $$H_2N-CH_2-COOH$$
2. A proton ($H^+$) transfers from the acidic carboxyl group to the basic amino group
3. The resulting zwitterion has an overall charge of zero:

   $$^+H_3N-CH_2-COO^-$$

**Check your understanding**

Check your understanding of pH effects

1. What is the overall charge of glycine at pH 1 (strongly acidic)?

   - Negative (-1)
   - Zero
   - Positive (+1)
   - Depends only on the R-group

   *Why:* In acidic conditions, the carboxylate ion accepts a proton to become neutral $-COOH$, while the amino group remains protonated $-NH_3^+$, giving an overall charge of +1.

## Effect of pH on Amino Acid Charge

The overall charge of an amino acid depends directly on the pH of the solution, due to protonation and deprotonation of ionisable groups. At low pH (acidic conditions), high $H^+$ concentration means the carboxylate group accepts a proton, leaving the amino group protonated, giving an overall charge of +1. At high pH (alkaline conditions), high $OH^-$ concentration removes a proton from the protonated amino group, leaving the carboxyl group deprotonated, giving an overall charge of -1.

**Isoelectric point (pI)** — The pH at which an amino acid exists predominantly as a zwitterion, with no overall net charge

**Worked example:** Draw the structure of alanine at pH 12 (strongly alkaline) and state its overall charge. Alanine has $R = -CH_3$, a neutral side chain.

1. At high pH, all acidic groups are deprotonated, and all protonated basic groups lose their protons.
2. Alanine only has one carboxyl and one amino group: the amino group becomes $-NH_2$ (neutral) and the carboxyl group becomes $-COO^-$ (-1 charge):

   $$H_2N-CH(CH_3)-COO^-$$
3. Adding the charges: $0 + (-1) = -1$, so the overall net charge is -1.

> **Exam tip:** Always account for ionisable R-groups (acidic $-COOH$ or basic $-NH_2$) when calculating overall charge, they add extra charges that are easy to miss.

## Classification and Key Reactions

Amino acids are classified as essential or non-essential based on whether the human body can synthesise them. Non-essential amino acids are produced by the body, while essential amino acids must be obtained from the diet. Amino acids undergo all reactions typical of amines and carboxylic acids, including esterification of the carboxyl group and acylation of the amino group.

**Worked example:** Write the balanced equation for esterification of glycine with excess ethanol under acidic conditions.

1. In acidic conditions, the amino group is protonated ($-NH_3^+$) and the carboxyl group is un-ionised ($-COOH$), which undergoes esterification with alcohol.
2. The reaction produces an ester and water, as shown:

   $$^+H_3N-CH_2-COOH + C_2H_5OH \rightleftharpoons ^+H_3N-CH_2-COOC_2H_5 + H_2O$$

## Common pitfalls

- **Wrong:** Assuming amino acids have an overall charge of zero at all pH values
  - Why it fails: Net charge changes with pH; only at the isoelectric point is charge zero
  - Correct: For any pH question, determine if the solution is acidic, neutral, or alkaline, then protonate/deprotonate all ionisable groups accordingly
- **Wrong:** Forgetting that R-groups can be ionisable and affect overall charge
  - Why it fails: Exam questions often use amino acids with acidic/basic side chains, ignoring these leads to incorrect charge values
  - Correct: Always check the R-group structure for additional ionisable groups when calculating net charge
- **Wrong:** Drawing zwitterions with a negative charge on the nitrogen atom
  - Why it fails: Proton transfer adds a proton to the amino group, so it carries a positive charge
  - Correct: Zwitterions of neutral amino acids always have $^+NH_3-$ (positive) and $-COO^-$ (negative)
- **Wrong:** Confusing essential and non-essential amino acids based on biological importance
  - Why it fails: Classification is based on whether the body can synthesise the amino acid, not how important it is
  - Correct: Remember: essential = must be obtained from diet, body cannot synthesise it; non-essential = body can make it

## Cheatsheet

| pH Condition | Dominant Structure (neutral R-group) | Overall Net Charge |
| --- | --- | --- |
| Strongly acidic (< pI) | $^+H_3N-CH(R)-COOH$ | +1 |
| At isoelectric point (= pI) | $^+H_3N-CH(R)-COO^-$ | 0 |
| Strongly alkaline (> pI) | $H_2N-CH(R)-COO^-$ | -1 |
| General un-ionised α-amino acid | $NH_2CH(R)COOH$ | 0 |

## What's next

Amino acids are the monomer building blocks that form peptides and proteins via condensation polymerisation. Understanding their structure and pH-dependent behaviour is critical to explaining protein solubility, electrophoresis, and denaturation. This topic forms the foundation for understanding how proteins fold and function, which is a core exam topic. It also links directly to earlier work on organic functional group reactions, which is often assessed alongside amino acid chemistry.

- [Carboxylic acid derivatives](https://www.owlsprep.com/study/cie-9701-u26-overview/)

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