Condensation Reactions

• Two molecules combine with the generation of a smaller molecule

Condensation Reactions

• Reaction of Acetic Acid and Ethanol

Looking at the Reaction Mechanism

1. The carbonyl carbon is:• Electron deficient• In a trigonal planar geometry

• 120º between substituents

2. The carbonyl oxygen is pulling electrons towards it

• Resonance stabilization3. The Lone Pair of the alcohol oxygen can react

with the carbonyl carbon to set the whole thing in motion

4. Remember your VSEPR Geometry

Condensation Reactions: Making Lipids from Sugars and Fatty Acids

• Your cells can synthesize lipids from glycerol and fatty acids in a condensation reaction

Condensation Reactions: Polymerizing Carbohydrate Monomers

Condensation Reactions: Forming a Peptide Bond

1. What are the amino acids in the figure?

2. What function group is formed?

Its not really this simple, but it illustrates a point!

Hydrolysis: The Opposite of Condensation

•In a hydrolytic reaction, we add the elements of water (H+ and OH-) across a bond

•Many enzymes use this kind of reaction to degrade polymers

•Lipases: Hydrolyze lipid esters

•Glycosidases: Hydrolyze carbohydrate polymers

•Peptidases: Hydrolyze peptide bonds

•Compound Name + ase : Usually indicates a hydrolase (but not always!)

•If it isn’t a compound name and ase, then it usually does something else:

•Lyase

•Reductase

•Kinase

•Transferase

Hydrolysis of Sugar Polymers

• We add water across the Glycosidic Bond of Maltose to break it and generate 2 monomers

• Catalyzed by a glycosidase (Maltase perhaps?)

Hydrolysis of Peptides

• Dipeptide (What are the amino acids) is hydrolyzed to ???

• Catalyzed by a peptidase or a protease

Amino Acids

• Amino acids are the building blocks of proteins

• They consist of an amino group bonded to an -carbon, a hydrogen bonded to the -carbon and a carboxylic acid

Amino Acids and Stereochemistry

• The -carbon is all amino acids except for glycine is chiral– Stereoisomers exist that is non-superimposable– Any carbon with 4 different substituents can be

chiral• We describe the chirality of the -carbon as

being Levorotary or Dextrorotary– L- or D-– Refers to how the molecule rotates polarized light

Amino Acids and Stereochemistry

Amino Acid Side Chains: Where the Action is!

• The amino acids are classified according to the chemical character of the R-grop attached to the -carbon

• Important Criteria:– Polar or Nonpolar side chains– Acidic or Basic– Charged or uncharged Polar residues

Side Chain Classification

1. Nonpolar (hydrophobic) Amino Acids

G, A, V, L, I, P, F, W, M

• These amino acids have aliphatic side chains

– Phenylalanine and Tryptophan are aromatic• Proline is cyclic

– Induces turns in proteins

Side Chain Classification

2. Polar, Uncharged Amino Acids

S, T, Y, C, N, Q

• S, T, Y have hydroxyl groups (-OH)• C has a sulfhydryl (-SH)• N and Q have amide side chains

– Uncharged at neutral pH

Side Chain Classification

3. Acidic Amino Acids

D and E have carboxylic acids on their side chains

• The side chains are negatively charged at neutral pH

– This means the pKa’s of the side chains are less than 7

Side Chain Classification

4. Basic Amino Acids

H, K and R have side chains that are positively charged at neutral pH

• Because these side chains have basic groups, they accept protons at pH values lower than the pKa of the side chain

Titrating Amino Acids

• Free amino acids can have up to 3 pKa values associated with them– Carboxylic acid– Amino group– R-group

• The carboxylic acid group has the lowest pKa (~2.0)

• The pKa of the -amino is around 9-10• D, E, H, C, Y, K and R have R-groups that can

ionize and their pKa’s range from ~4 to 12

Titrating and Amino Acid: Alanine1. We’ll start at a pH of 1

• The carboxylic acid and the amino group are protonated

2. As we start adding base, more and more of the carboxylic acids start losing protons until we reach pH 2.34 (the pKa of COOH)

3. At this concentration, [NH3

+CHCH3COOH]=[NH3+CHCH3COO-]

(same as we learned with regular titrations)

• As we add more base, we deprotonate all the carboxylic acids

2. Midway up the sharp slope increase

3. For alanine, this is the isoelectric point

• As we add more base, we’ll start deprotonating the -amino group until we reach pH=9.69 (the pKa of the group)

2. [NH3+CHCH3COO-]=[NH2CHCH3COO-]

• Finally we can keep adding base until the only species is: NH2CHCH3COO-

Titrating and Amino Acid: Histidine1. We’ll start at a pH of 1, the only species is

the fully protonated form.

• pK1 (COOH) = 1.82

• pK2 (Imidazole nitrogen) = 6.0

• pK3 (Amino) = 9.17

2. As we start adding base, the pH increases as the carboxylic acid converts to carboxylate

• At pK1, the concentration of the carboxylate specie equals the concentration of the carboxylic acid species

1. As we add more base, we start deprotonating the imidazole nitrogen

• At pK2, the conc. of the deprotonated imidazole group equals that of the protonated state

• The pI is reached then the imidazole group is completely deprotonated

• As we add more base, we’ll start deprotonating the -amino group until we reach pH=9.17 (the pKa of the group)

Amino Acid Titrations

• At the isoelectric point, the molecule has zero net charge• The pH where this occurs is called the pI• We can calculate the pI of an amino acid using the following equation:

• We average the pK values from the higher pKa that lost a hydrogen and the lowest pKa that is still protonated

• For example: Histidine– pK1 = 1.82– pK2 = 6.0– pK3 = 9.17– We’d use the last two values– Usually it will be the alpha amino and the R group pK’s that are used

€

pI = pK1 + pK2

2But we must take care to use the correct pK values!

The Peptide Bond

• Amino acids are joined together in a condensation reaction that forms an amide known as a peptide bond

The Peptide Bond

• A peptide bond has planar character due to resonance hybridization of the amide

• This planarity is key to the three dimensional structure of proteins