Lecture 3 amino acids
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Lecture 3: Amino Acids. Bonus seminar today at 3PM 148 Baker (bonus point assignment due on Wed. in class or electronically by email) Quiz next Wed. (9/7) Introduction to amino acid structure Amino acid chemistry. +. +. +. +. COO -. COO -. COO -. COO -. H 3 N. H 3 N. H 3 N. H 3 N.

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Lecture 3: Amino Acids

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Lecture 3 amino acids

Lecture 3: Amino Acids

  • Bonus seminar today at 3PM 148 Baker (bonus point assignment due on Wed. in class or electronically by email)

  • Quiz next Wed. (9/7)

  • Introduction to amino acid structure

  • Amino acid chemistry


Uncharged polar side chains

+

+

+

+

COO-

COO-

COO-

COO-

H3N

H3N

H3N

H3N

C

C

H

H

C

C

H

H

H

C

OH

H

CH2

CH2

CH3

Glycine

Gly

G

OH

Serine

Ser

S

Threonine

Thr

T

OH

Tyrosine

Tyr

Y

Uncharged polar side chains


Uncharged polar side chains1

+

H3N

Uncharged polar side chains

COO-

C

H

R-S- + H+

R-SH

CH2

SH

R-O- + H+

R-OH

Cysteine

Cys

C


Formation of cystine

Formation of cystine


Uncharged polar side chains2

+

+

COO-

COO-

H3N

H3N

C

C

H

H

CH2

CH2

C

CH2

O

NH2

C

Asparagine

Asn

N

O

NH2

Glutamine

Gln

Q

Uncharged polar side chains


Amino acids

Amino acids

  • Polar, uncharged amino acids

    • Contain R-groups that can form hydrogen bonds with water

    • Includes amino acids with alcohols in R-groups (Ser, Thr, Tyr)

    • Amide groups: Asn and Gln

    • Usually more soluble in water

      • Exception is Tyr (most insoluble at 0.453 g/L at 25 C)

    • Sulfhydryl group: Cys

      • Cys can form a disulfide bond (2 cysteines can make one cystine)


Charged polar acidic side chains

+

+

COO-

COO-

H3N

H3N

C

C

H

H

Charged polar (acidic) side chains

CH2

CH2

CH2

C

C

O

O-

O

O-

Aspartic acid

Asp

D

Glutamic acid

Glu

E


Amino acids1

Amino acids

  • Acidic amino acids

    • Amino acids in which R-group contains a carboxyl group

    • Asp and Glu

    • Have a net negative charge at pH 7 (negatively charged pH > 3)

    • Negative charges play important roles

      • Metal-binding sites

      • Carboxyl groups may act as nucleophiles in enzymatic interactions

      • Electrostatic bonding interactions


Charged polar basic side chains

+

+

+

COO-

COO-

H3N

H3N

H3N

C

C

H

H

Charged polar (basic) side chains

COO-

C

H

CH2

CH2

CH2

CH2

CH2

CH2

CH2

C

HC

NH

CH2

NH

H+N

C

NH3+

CH

NH2

NH2+

Lysine

Lys

K

Histidine

His

H

Arginine

Arg

R


Amino acids2

Amino acids

  • Basic amino acids

    • Amino acids in which R-group have net positive charges at pH 7

    • His, Lys, and Arg

    • Lys and Arg are fully protonated at pH 7

      • Participate in electrostatic interactions

    • His has a side chain pKa of 6.0 and is only 10% protonated at pH 7

    • Because His has a pKa near neutral, it plays important roles as a proton donor or acceptor in many enzymes.

    • His containing peptides are important biological buffers


Nonstandard amino acids

Nonstandard amino acids

  • 20 common amino acids programmed by genetic code

  • Nature often needs more variation

  • Nonstandard amino acids play a variety of roles: structural, antibiotics, signals, hormones, neurotransmitters, intermediates in metabolic cycles, etc.

  • Nonstandard amino acids are usually the result of modification of a standard amino acid after a polypeptide has been synthesized.

  • If you see the structure, could you tell where these nonstandard amino acids were derived from?


Nonstandard amino acids1

Nonstandard amino acids


Nonstandard amino acids2

Nonstandard amino acids


Peptide bonds

+

+

O

R2

O

R1

H

H3N

H3N

O-

C

C

OH

C

C

H

N

H

H

O

R2

O

R1

O-

C

C

C

N

C

H

H

H

+ H2O

Peptide bonds

  • Proteins are sometimes called polypeptides since they contain many peptide bonds

+


Structural character of amide groups

Structural character of amide groups

  • Understanding the chemical character of the amide is important since the peptide bond is an amide bond.

  • These characteristics are true for the amide containing amino acids as well (Asn, Gln)

  • Amides will not ionize:

O

O

NH2

R

C

NH2

R

C


Acid base properties of amino acids

Acid-base properties of amino acids

The dissociation of first proton from the -carboxyl group is

The dissociation of the second proton from the -amino group

Gly0 + H2O

Gly- + H3O+

Gly+ + H2O

Gly0 + H3O+

[Gly0][H3O+]

[Gly-][H3O+]

K1=

K2=

[Gly+]

[Gly0]

The pKa’s of these two groups are far enough apart that they can be approximated by Henderson-Hasselbalch

[Gly0]

[Gly-]

pK1 + log

pK2 + log

pH =

pH =

[Gly+]

[Gly0]


Titration curve of glycine

+

H3N

COO-

Neutral

form

C

H

H

Titration curve of glycine


Titration of gly

+

+

H3N

H2N

H3N

COO-

COOH

COO-

C

H

C

C

H

H

pK1

pK2

H

H

H

Gly+

Gly-

Gly0

Titration of Gly

pH 2.3

pH 9.6

From the pK values we can calculate the pI (isoelectric point) where the amino acid is neutral.

pI ≈ average of (pK below neutral+ pKabove neutral)

So, for Gly,

pI = (pK1 + pK2)/2

= (2.3 + 9.6)/2 ≈ 6


General rules for amino acid ionization

General rules for amino acid ionization

  • Alpha carboxylic acids ionize at acidic pH and have pKs less than 6; So in titrating a fully protonated amino acid, alpha carboxylic acids lose the proton first.

  • Alpha amino groups ionize at basic pH and have pKs greater than 8; So after acids lose their protons, amino groups lose their proton.

  • Most of the 20 amino acids are similar to Gly in their ionization properties because their side chains do not ionize at biological pHs.

  • However, there are 5 exceptions worth noting (the amino acids with polar charged side chains)

  • Glu, Asp, Lys, Arg, His

  • Each has 3 ionizible groups and thus, 3 pKs.


Lecture 3 amino acids

+

+

COOH

COOH

H3N

H3N

C

C

H

H

CH2

CH2

CH2

C

C

O

OH

O

OH

Aspartic acid

Asp

D

Glutamic acid

Glu

E

Charged polar (acidic) side chains

2.1

2.0

9.5

9.8

3.9

4.1


How to calculate the pi of a compound with more than 2 p k s

How to calculate the pI of a compound with more than 2 pKs

  • Find the amino acid form with no net charge (total charge = 0).

  • Take the pK of the amino acid form going towards +1 form as the lower pK.

  • Next find the amino acid form going towards the -1 form.

  • Finally, average these two pKs to get the pI.


Titration curve of aspartic acid

Titration curve of aspartic acid

The neutral form of Asp is close to pH 2.8

Take the pKs for +1 and -1 from this point and average to get approximate pI,

pI = (pK3 + pK1)/2 = (2.0 + 3.9)/2 = 2.95


Lecture 3 amino acids

+

+

+

COOH

COOH

H3N

H3N

H3N

C

C

H

H

Charged polar (basic) side chains

1.8

2.2

1.8

COOH

9.2

9.3

C

H

9.0

CH2

CH2

CH2

CH2

CH2

CH2

CH2

C

HC

6.0

NH

CH2

NH

H+N

C

NH3+

CH

NH2

NH2+

Lysine

Lys

K

10.8

Histidine

His

H

Arginine

Arg

R

12.5


Titration curve of arginine

Titration curve of arginine

The neutral form of Asp is close to pH 10.8

Take the pKs for +1 and -1 from this point and average to get approximate pI,

pI = (pK2 + pK3)/2 = (9.0 + 13.0)/2 = 11.0


Acid base properties of amino acids1

Acid-base properties of amino acids


More rules for amino acid ionization

More rules for amino acid ionization

  • Carboxylic acid groups near an amino group in a molecule have a more acidic pK than isolated carboxylic groups.

  • Amino groups near a carboxylic acid group also have a more acidic pK than isolated amines.

  • Aromatic amines like His have a pK about pH 6.

  • When titrating an amino acid that is fully protonated (ie starting at pH = 1), the alpha carboxylic acids lose their proton first (all free amino acids have this group), then side chain carboxylic acids, then aromatic amine side chains (His), then alpha amino groups, then side chain amino groups.

  • These rules apply to small peptides too.


Amino acids are optically active

Amino acids are optically active

  • All amino acids are optically active (exception Gly).

  • Optically active molecules have asymmetry; not superimposable (mirror images)

  • Central atoms are chiral centers or asymmetric centers.

  • Enantiomers -molecules that are nonsuperimposable mirror images


Asymmetry

Asymmetry

  • Molecules are classified as Dextrorotatory (right handed), D or Levrotatory (left handed) L depending on whether they rotate the plane of plane-polarized light clockwise or counterclockwise determined by a polarimeter


Asymmetry1

Asymmetry

  • Fischer projections are a shorthand way to write molecules with chiral centers


Asymmetry2

Asymmetry

  • For -amino acids the arrangement of the amino, carboxyl, R, and H groups about the C atom is related to glyceraldehyde


Asymmetry3

Asymmetry

  • All -amino acids from proteins have the L-stereochemical configuration


Diastereomers

Diastereomers

  • Stereoisomers or optical isomers are molecules with different configurations about at least one of their chiral centers but are otherwise identical

  • Since each asymmetric center in a chiral molecule can have two possible configurations, a molecule with n chiral centers has 2n different possible stereoisomers and 2n-1enantiomeric pairs

  • Ex. Threonine and Isoleucine both have two chiral centers, and thus 4 possible stereoisomers.


Diastereomers1

Diastereomers

*

*


Diastereomers2

Diastereomers

  • Special case: 2 asymmetric centers are chemically identical (2 asymmetric centers are mirror images of one another)

  • A molecule that is superimposable on its mirror image is optically inactive (meso form)


Cahn ingold prelog or rs system

Cahn-Ingold-Prelog or (RS) System

  • The 4 groups surrounding a chiral center a ranked as follows: Atoms of higher atomic number bonded to a chiral center are ranked above those of lower atomic number.

  • Priorities of some common functional groups SH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > CH3 > 2H > 1H

  • Prioritized groups are assigned letters W, X, Y, Z, so that W > X > Y > Z

  • Z group has the lowest priority (usually H) and is used to establish the chiral center.

  • If the order of the groups W X Y is clockwise, as viewed from the direction of Z, the configuration is (R from the latin rectus, right)

  • If the order of the groups W X Y is counterclockwise, as viewed from the direction of Z, the configuration is (S from the latin sinister, left)


Cahn ingold prelog or rs system1

Cahn-Ingold-Prelog or (RS) System


Cahn ingold prelog or rs system2

Cahn-Ingold-Prelog or (RS) System


Cahn ingold prelog or rs system3

Cahn-Ingold-Prelog or (RS) System


Prochiral centers have distinguishable substituents

Prochiral centers have distinguishable substituents

  • Prochiral molecules can be converted from an achiral to chrial molecule by a single substitution

  • Molecules can be assigned a right side and left side for two chemically identical substituents.

  • True for tetrahedral centered molecules

  • Example is ethanol


Prochiral centers

Prochiral centers


Planar objects can also be prochiral

Planar objects can also be prochiral

  • Stereospecific additions in enzymatic reactions

  • If a trigonal carbon is facing the viewer so that the substituents decrease in a clockwise manner it is the re face

  • If a trigonal carbon is facing the viewer so that the substituents decrease in a counterclockwise manner it is the si face

  • Acetaldehyde example


Nomenclature

Nomenclature

  • Glx can be Glu or Gln

  • Asx can be Asp or Asn

  • Polypeptide chains are always described from the N-terminus to the C-terminus


Nomenclature1

Nomenclature

  • Nonhydrogen atoms of the amino acid side chain are named in sequence with the Greek alphabet


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