understanding amino acids and proteins

8/6/2019 Understanding Amino Acids and Proteins

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AMINO ACIDS, PEPTIDES, AND PROTEINS

REVIEW

(I) Carboxylic Acid

y Properties of Carboxylic Acid In aqueous solution, carboxylic acid is in equilibrium with carboxylate ion whose negative

charge is delocalized over two equivalent oxygen atoms (resonance). p.755

Generally,

In acidic solution at low pH, carboxylic acid is almost completely undissociated and exists

almost entirely as RCO2H. p.758

In basic solution at high pH, carboxylic acid is almost completely dissociated and exists

almost entirely as RCO2-. p.758

At physiological pH of 7.3 , carboxylic acids are mostly dissociated. p.758

[See appendix for acidity of some common carboxylic acids.]


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y Substituent Effects on Acidity of Carboxylic AcidsBecause the dissociation of carboxylic acid is an equilibrium process, any factor that

stabilizes the carboyxlate anion will drive equilibrium to the right and result in increased

acidity. p.759

For example,

[Note: chlorine is an electron-withdrawing atom.]

(II) Amines

Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been

replaced by a substituent such as an alkyl or aryl group.

http://en.wikipedia.org/wiki/Amine

Heterocylic amines, compounds in which the nitrogen at om occurs as part of a ring, are

common. p.918


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y Properties of Amines Amines contain a nitrogen atom with a lone pair of electrons, making amines both basic and

nucleophilic. p.916

In aqueous solution, equilibrium is established in which water acts as an acid and transfers a

proton to the amine. p.921

[See appendix for basicity of some common amines.]

Generally,

In acidic solution at low pH , almost all amines are protonated. p.927

In basic solution at high pH , almost all amines are unprotonated. p.927

At physiological pH of 7.3 , amines are mostly protonated. p.927

y ArylaminesArylamines are generally less basic than alkylamines due to resonance. p.924


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idin

e

y

es

y

es are

as

c

as s

rong as alkylamines

p.949

(pKa = 5.25

i

!idin

: It is weakly basic (due to inductivee

ect of thesecond nitrogen). p.950

"

# # #

$

%

& '

tion of C&

box

li'

A'

id with A!

in

Since amines are basic and carboxylic acid groups are acidic we have an acid and base

reaction.

RNH2 + RCOOH

RNH3+

+ RCO2-

carboxylatesalt

Heating thecarboxylatesalt above100oC will cause dehydration, thus forming amide.The

overall reaction is:

This reaction iscommonly found in living organisms. But instead of producing amide as

shown above, the reaction is facilitated bycomplex enzyme mechanisms.

http://homepage.mac.com/tminehan/spring334pdfs/11&12Bnew.pdf

http://www.mnstate.edu/jasperse/Chem360/Handouts/Ch%2019%20Reactions%20%28p%

201-6%29.pdf


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(

)V

0

A1

id2

s

Amides (RCONH2) are nonbasic and are poor nucleophiles, unlike amines. This is because

amides are hybrids of two resonance forms. p.922

(

V0

3

hiols

Thiols arecompounds having thestructure RSH where R H.

http://goldbook.iupac.org/T06359.html

Thiolscan be oxidized (ie. byBr2 or I2) to yield disulfides (RSSR). The reaction iseasily

reversed, and a disulfidecan be reduced (ie. by zinc and acid) back to a thiol.p.668

[Advanced: In cells the oxidizing agent can be H2O2 and the reducing agent can beFADH2.]

A4 )

N5

AC) 6

7

A1

ino8 9

ids are moleculescontaining an amino group, carboxyl group, sidechain and

hydrogen attached to thecentral carbon. They are difunctional as theycontain both a

carboxyl group (acidic) and an amino group (basic).


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Recall that at physiological pH of 7.3, carboxyl group is deprotonated while amino group is

protonated. Thus, amino acids exist in aqueous solution primarily in the form of a diplor ion,

also called z@

itterion.

A zwitterions is a compound with no overall electrical charge, but contains separate partswhich are positively and negatively charged.

Amino acid zwitterions are internal salts and therefore have many of the physical properties

associated with salts. They are soluble in water but insoluble in hydrocarbons. p.1017

--------------------

Amino acids are also amphiprotic: they can react as acids or as bases, depending on the

circumstances.

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Nearly all proteins in all species are built from the same 20A

- amino acids. They are called

alpha amino acids because the amine is attached to the carbon in the alpha position to the

carbonyl. In humans, ten of the amino acids are essential. In other words the body cannot

manufacture these 10, so they must be ingested directly.

Nineteen of the twenty amino acids are primary amines, RHN2, and differ only in the nature

of the side chain attached to theB

carbon. Proline is a secondary amine and the only

amino acid whose nitrogen and E carbon atoms are part of a ring.

Except for glycine, H2NCH2COOH, the E carbons of amino acids are chirality centers. Two

enantiomers of each are therefore possible, but nature uses only one to build proteins. The

naturally occurring E - amino acids are often referred to as L amino acids. The nonnaturally

occurring enantiomers are called Damino acids.


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CLASSIFICATION OF AMINO ACIDS

The 20 common amino acids can be further classified as neutral, acidic or basic, depending

on the structure of their side chains. Fifteen of the t wenty have neutral side chains, two

(aspartic acid and glutamic acid) have an extra carboxylic acid function in their side chains,

and three (lysine, arginine, and histidine) have basic amino groups in their side chains. Note

that both cysteine and tyrosine, although usually classified as neutral, nevertheless have

weakly acidic side chains that can be deprotonated in a sufficiently basic solution.

At physiological pH of 7.3, the side-chain carboxyl groups of aspartic acid and glutamic acid

are deprotonated and the basic side-chain nitrogens of lysine and arginine are protonated.

Histidine, however, which contains a heterocyclic imidazole ring in its side chain, is not quite

basic enough to be protonated at pH 7.3. Note that only the pyridine -like doubly bonded

nitrogen in histidine is basic. The other is nonbasic because its lone pair of electrons forms

part of the aromaticity.


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Amino acids may also be classified as polar or non-polar according to their side chains. See

below. (For details, see appendix)


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ISOELECTRIC POINTS

In acid solution, an amino acid is protonated and exists primarily as a cation. In basic

solution, an amino acid is deprotonated and exists primarily as an anion.

The isoelectric point of an amino acid is the pH value at which the amino acid is exactly

balanced between anionic and cationic forms. The ioselectric point is dependent on the

structure of the amino acid. In particular, the side chain of the amino acid determines theisoelectric point.

We can take advantage of the differences in isoelectric points to separate a mixture of

amino acids. Using a technique known as electrophoresis , a mixture of amino acids is placed

near the center of a strip of paper or gel. The paper or gel is moistened with an aqueous

buffer of a given pH, and electrodes are connected to the ends of the strip. When an electric

potential is applied, those amino acids with negative charges (those that are deprotonated

because the pH of the buffer is above their isoelectric poin t) migrate slowly toward the

positive electrode. At the same time, those amino acids with positive charges (those that

are protonated because the pH of the buffer is below their isoelectric point) migrate toward

the negative electrode.

Different amino acids migrate at different rates, depending on their isoelectric points and on

the pH of the aqueous buffer, thereby separating the mixture.

[Note: the separated amino acids are made visible by spraying with ninhydrin.]


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POLYPEPTIDES AND PROTEINS

In nature, individual amino acids are linked together in chains as polypeptides and proteins.

The amino acids found in polypeptides or proteins are known as residues.

The diagrams below show the condensation of the amino acids alanine and serine to form a

depeptide. The amino acids are bonded together by a peptide link (amide bond) .


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Each peptide link forms:

y between the carboxyl group and an amino groupy with loss of a water moleculeFurther condensation reactions between amino acids build up a polypeptide or protein.

y For each amino acid added to a protein chain, one water molecule is lost.y Most common proteins contain more than 100 amino acids.The long, repetitive sequence of -N-CH-CO- atoms that make up a continuous chain is called

the proteins backbone. By convention, peptides are written with the N-terminal amino

acid (the one with the free -NH2 group) on the left and the C-terminal amino acid (the one

with the free -CO2H group) on the right.

The amide bond that links different amino acids together in peptides is no different from

any other amide bond. Amide nitrogens are nonbasic because their unshared electron pair

is delocalized by interaction with carbonyl group.

Hydrolysis breaks down a protein into its separate amino acids. For example,


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A second kind of covalent bonding in peptides occurs when a disulfide linkage, RS -SR, is

formed between two cysteine residues. A disulfide is formed by mild oxidation of a th iol,

RSH, and is cleaved by mild reduction.

A disulfide bond between cysteine residues in different peptide chains links the otherwise

separate chains together, while a disulfide bond between cysteine residues in the same

chain forms a loop.

PROTEIN STRUCTURE

Proteins are usually classified as either fibrous or globular, according to their three-dimensional shape. Fibrous proteins, such as the collagent in tendons and connective tissue

and the myosin in muscle tissueee, consists of polypeptid e chainsss arranged side by side in

long filaments. Because these proteins are tough and insoluble in water, they are used in

nature of structural materials. Globular proteins , by contrast, are usually coled into

compact, roughly spherical shapes. These proteins are generally soluble in water and are

mobile within cells.Most of the 3000 or so enzymes that have been characterized to date

are globular proteins.

Proteins are so large that the word structure takes on a broader meaning than it does with

simpler organic compounds. In fact, chemists speak of four different levels of structure

when describing proteins:


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Primary Structure

The primary structure of a protein is the actual sequence of amino acidsjoined by peptide

links.

eg. ala-gly-lys-cys-asn-arg-gly-leu-try-val..

Secondary Structure

The secondary structure of a protein is a region in which there are regular structures. There

are two types, an E -helix and a F -sheet, each held together by hydrogen bonds between

C=O and N-H.


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Tertiary Structure

The tertiary structure refers to the three dimensional shape formed when the peptide chain

curls and folds. Five forces create the tertiary structure.

(1) covalent disulfide bonds between two cysteine amino acids on different part of the

chain;

(2) electrostatic (ionic) interactions mostly between acidic and basic side chains such as -

CH2COO-

and NH3+;

(3) hydrogen bonds between polar side chains such as C H2OH and CH2CONH2;

(4) Van der Waals forces;

(5) hydrophobic side chains pushed away from water (toward the center) of protein.

Quaternary Structure

When two or more polypeptide chians bind together, they form the quaternary structure of

the protein. The same five forces at work in the tertiary structure can also act to form the

quaternary structure.

-------------------

When the conformation is disrupted, the protein is said to be denatured. A denaturedprotein has lost most of its secondary, tertiar y, and quaternary structure. Denaturation is

accompanied by changes in both physical and biological properties. Solubility is drastically

decreased (usually).Most enzymes also lose all catalytic activity when denatured, since a

precisely defined tertiary structure is required for their action. Although most denaturation

is irreversible, cases are also known where spontaneous renaturation of an unfolded protein

to its stable tertiary structure occurs. Renaturation is accompanied by a full recovery of

biological activity.


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APPENDIX

p.756


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p.923


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understanding amino acids and proteins

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