Amino Acids NH3NH3NH3NH3+ CO2CO2CO2CO2 – an  -amino acid that is an intermediate in the biosynthesis of ethylene + H 3 NCH 2 CH 2 CO 2 – a  -amino acid that is one of the structural units present in coenzyme A + H 3 NCH 2 CH 2 CH 2 CO 2 – a  -amino acid involved in the transmission of nerve impulses    They are classified as , , , etc. amino acids according the carbon that bears the nitrogen.

Table 27.1 CCOO – RR H H3NH3NH3NH3N + The major differences among the side chains: Size and shape Electronic characteristics Glycine is achiral. All of the other amino acids in proteins have the L -configuration at their  carbon.

Table 27.1 General categories of  -amino acids nonpolar side chains polar but nonionized side chains acidic side chains basic side chains

Properties of Glycine The properties of glycine: high melting point: (when heated to 233°C it decomposes before it melts) solubility: soluble in water; not soluble in nonpolar solvent O OH H 2 NCH 2 C – O O H 3 NCH 2 C + more consistent with this than this called a zwitterion or dipolar ion

Acid-Base Properties of Glycine The zwitterionic structure of glycine also follows from considering its acid-base properties. A good way to think about this is to start with the structure of glycine in strongly acidic solution, say pH = 1. At pH = 1, glycine exists in its protonated form (a monocation). OOH H 3 NCH 2 C +

Acid-Base Properties of Glycine Therefore, the more stable neutral form of glycine is the zwitterion. OOH H 3 NCH 2 C + typical carboxylic acid: pK a ~5 – OO H 3 NCH 2 C +

The measured pK a of glycine is Glycine is stronger than a typical carboxylic acid because the positively charged N acts as an electron-withdrawing, acid-strengthening substituent on the  carbon. Acid-Base Properties of Glycine OOH H 3 NCH 2 C + typical carboxylic acid: pK a ~5

Acid-Base Properties of Glycine – OO H 3 NCH 2 C + The pK a for removal of this proton is This value is about the same as that for NH 4 + (9.3). HO– – OO H 2 NCH 2 C A proton attached to N in the zwitterionic form of nitrogen can be removed as the pH is increased further.

Isoelectric Point pI – OO H 3 NCH 2 C + – OO H 2 NCH 2 C OOH H 3 NCH 2 C + pK a = 2.34 pK a = 9.60 The pH at which the concentration of the zwitterion is a maximum is called the isoelectric point. Its numerical value is the average of the two pK a s. The pI of glycine is Can be used for identification or purification

Titration Curve Alanine

Table 27.3 Amino Acids with Acidic Side Chains Aspartic acid pK a1 = 1.88 pK a2 =3.65 pK a3 =9.60 pI =2.77 H3NH3NH3NH3N CC O O – H + OCCH 2 O– For amino acids with acidic side chains, pI is the average of pK a1 and pK a2.

Table 27.3 Amino Acids with Basic Side Chains Lysine pK a1 = 2.18 pK a2 =8.95 pK a3 =10.53 pI =9.74 H3NH3NH3NH3N CCOO – H + CH 2 CH 2 CH 2 CH 2 NH 3 + For amino acids with basic side chains, pI is the average of pK a2 and pK a3.

Synthesis of Amino Acids From  -Halo Carboxylic Acids CH 3 CHCOH BrO 2NH32NH32NH32NH3 + H2OH2OH2OH2O CH 3 CHCO NH3NH3NH3NH3O+ – (65-70%) + NH 4 Br

Strecker Synthesis NH 4 Cl NaCN CH 3 CH O CH 3 CHC NH2NH2NH2NH2N CH 3 CHCO NH3NH3NH3NH3 O + – (52-60%) 1. H 2 O, HCl, heat 2. HO –

Using Diethyl Acetamidomalonate C C C OCH 2 CH 3 HOO CH 3 CH 2 O CH 3 CNH O Can be used like as diethyl malonate.

Example 1. NaOCH 2 CH 3 2. C 6 H 5 CH 2 Cl O O CH 3 CH 2 OCCCOCH 2 CH 3 H CH 3 CNH O O O CH 3 CH 2 OCCCOCH 2 CH 3 CH 2 C 6 H 5 CH 3 CNH O (90%)

Example O O CH 3 CH 2 OCCCOCH 2 CH 3 CH 2 C 6 H 5 CH 3 CNH O HBr, H 2 O, heat O O HOCCCOH CH 2 C 6 H 5 H3NH3NH3NH3N + O HCCOH H3NH3NH3NH3N + (65%) –CO 2

Acylation of Amino Group The amino nitrogen of an amino acid can be converted to an amide with the customary acylating agents. O H 3 NCH 2 CO –++ CH 3 COCCH 3 OO CH 3 CNHCH 2 COH O O (89-92%)

Esterification of Carboxyl Group The carboxyl group of an amino acid can be converted to an ester. The following illustrates Fischer esterification of alanine. + CH 3 CH 2 OH HClO H 3 NCHCO – + CH 3 (90-95%)O H 3 NCHCOCH 2 CH 3 + CH 3 – Cl

Ninhydrin Test Amino acids are detected by the formation of a purple color on treatment with ninhydrin. OH O O OH +O H 3 NCHCO – + R O O O N O –ORCH + CO 2 + H2OH2OH2OH2O +

Decarboxylation Decarboxylation is a common reaction of  - amino acids. An example is the conversion of L -histidine to histamine. Antihistamines act by blocking the action of histamine. CH 2 CHCO 2 – NH3NH3NH3NH3 + NHNHNHNH N CH 2 CH 2 NH 2 NHNHNHNH N enzymes + CO 2,

Neurotransmitters OHOHOHOH CO 2 – H H H H3NH3NH3NH3N + L -3,4-Dihydroxyphenylalanine HOHOHOHO L -DOPA for Parkinsons Disease OHOHOHOH CO 2 – H H H H3NH3NH3NH3N + L -Tyrosine OHOHOHOH H H H H2NH2NH2NH2N HOHOHOHO Dopamine

Neurotransmitters OHOHOHOH H H H OH H2NH2NH2NH2N HOHOHOHO Norepinephrine OHOHOHOH H H OH HOHOHOHO Epinephrine CH 3 NH H

Peptides Peptides are compounds in which an amide bond links the amino group of one  -amino acid and the carboxyl group of another. An amide bond of this type is often referred to as a peptide bond. CH 3 OC H3NH3NH3NH3N + H C O C N H H C O – H Alanylglycine N-terminusC-terminus Ala—GlyAG