AMINO ACIDS – Comprehensive Exam Notes

Introduction to Amino Acids

Amino acids are fundamental organic compounds that serve as the building blocks of proteins. They are characterized by the presence of two primary functional groups and a unique side chain (R group) that imparts specific properties to each amino acid.

Structural Definition

General formula:

H2N—C—COOH

 |

 R

Where the amino group (-NH₂) is basic, and the carboxyl group (-COOH) is acidic. The side chain (R group) varies among amino acids, determining their distinct chemical and physical properties.

Key Structural Features

There are 20 standard amino acids that are incorporated into proteins.
All are α-amino acids, meaning the amino group is attached to the carbon atom adjacent to the carboxyl group.
Except for glycine, all amino acids are chiral and possess a stereocenter at the α-carbon, making them optically active.
In naturally occurring proteins, amino acids predominantly exist in the L-configuration, which is crucial for biological functions.

Biological Significance of Amino Acids

Function	Description	Examples
Protein Synthesis	Form the structural and functional components of all proteins	All 20 amino acids
Neurotransmitter Production	Serve as precursors for neurotransmitters in the nervous system	Glutamate, GABA, Glycine, Serine
Hormone Precursors	Precursor molecules for vital hormones	Tyrosine → Thyroid hormones, Catecholamines; Tryptophan → Serotonin, Melatonin
Nitrogen Transport	Transport nitrogen in the bloodstream	Alanine, Glutamine
Energy Production	Deaminated amino acids enter the TCA cycle for energy	Glucogenic amino acids
Gluconeogenesis	Precursor molecules for glucose synthesis	Alanine, Glutamine, Aspartate
Fatty Acid Synthesis	Provide carbon skeletons for lipid biosynthesis	Citrate derived from amino acids
Nucleic Acid Synthesis	Contribute nitrogen and carbon for purines and pyrimidines	Glycine, Aspartate, Glutamine
Heme Synthesis	Essential for hemoglobin and other hemoproteins	Glycine
Creatine Synthesis	Energy storage in muscles	Glycine, Arginine, Methionine
Detoxification	Convert ammonia to urea for excretion	Glutamate, Arginine

Classification of Amino Acids

1. Based on Chemical Structure (R group nature)

A. Aliphatic Amino Acids

R groups are alkyl chains. Examples include Glycine, Alanine, Valine, Leucine, Isoleucine.

Glycine (Gly, G): Smallest, no chiral center, flexible
Alanine (Ala, A): Simple aliphatic
Valine (Val, V): Branched chain
Leucine (Leu, L): Branched chain
Isoleucine (Ile, I): Branched chain

B. Hydroxyl Group Containing

Examples include Serine and Threonine, which are involved in phosphorylation and other modifications.

Serine (Ser, S): Site of phosphorylation
Threonine (Thr, T): Has two chiral centers

C. Sulfur Containing

Includes Cysteine and Methionine, important for disulfide bonds and methyl group donation.

Cysteine (Cys, C): Forms disulfide bonds (-S-S-)
Methionine (Met, M): Essential amino acid, methyl donor

D. Acidic Amino Acids and Their Amides

Examples include Aspartic acid, Glutamic acid, Asparagine, Glutamine.

Aspartic acid (Asp, D): Negative charge at physiological pH
Glutamic acid (Glu, E): Negative charge
Asparagine (Asn, N): Neutral
Glutamine (Gln, Q): Neutral

E. Basic Amino Acids

Includes Lysine, Arginine, Histidine, which carry positive charges at physiological pH.

Lysine (Lys, K): Positively charged
Arginine (Arg, R): Positively charged, guanidino group
Histidine (His, H): Partial positive charge, imidazole ring

F. Aromatic Amino Acids

Contain aromatic rings, involved in UV absorption and precursor roles.

Phenylalanine (Phe, F): Essential, precursor for tyrosine
Tyrosine (Tyr, Y): Precursor for catecholamines
Tryptophan (Trp, W): Essential, precursor for serotonin and melatonin

G. Imino Acid

Proline (Pro, P): Cyclic structure, disrupts secondary structures like α-helices.

2. Based on Polarity and Hydrophobicity

Non-polar (Hydrophobic): Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp
Polar Uncharged (Hydrophilic): Ser, Thr, Cys, Tyr, Asn, Gln
Polar Negative (Acidic): Asp, Glu
Polar Positive (Basic): Lys, Arg, His

3. Nutritional Classification

Essential Amino Acids: Cannot be synthesized by the body; must be obtained from diet. Includes Val, Leu, Ile, Lys, Met, Phe, Thr, Trp, His, Arg (in children).
Non-essential Amino Acids: Synthesized by the body. Includes Ala, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser, Tyr.
Conditionally Essential: Required under certain conditions like illness or stress. Includes Arg, Cys, Gln, Tyr, His, Pro, Gly.

4. Metabolic Fate

Glucogenic: Can be converted to glucose via TCA cycle intermediates. Examples: Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Met, Pro, Ser, Thr, Val.
Ketogenic: Can be converted to ketone bodies. Examples: Leu, Lys.
Both: Can form both glucose and ketone bodies. Examples: Ile, Phe, Trp, Tyr.

5. Side Chain pKa and Ionization

Amino acids with ionizable side chains have specific pKa values, influencing their charge at different pH levels. For example, Asp (pKa ≈ 3.86), Glu (pKa ≈ 4.25), His (pKa ≈ 6.00), Cys (pKa ≈ 8.33), Tyr (pKa ≈ 10.07), Lys (pKa ≈ 10.53), Arg (pKa ≈ 12.48).

Physical and Chemical Properties

Physical Properties

Colorless, crystalline solids
Taste varies: sweet (Gly, Ala), tasteless (Leu), bitter (Arg, Ile)
Soluble in water; insoluble in organic solvents
High melting points (>200°C)
Optically active (except glycine)

Chemical Properties

Zwitterion Formation

At neutral pH, amino acids exist as zwitterions with both positive and negative charges, crucial for their behavior in electrophoresis and solubility.

Ionic Behavior and pI

The isoelectric point (pI) is the pH at which the amino acid has zero net charge, calculated based on pKa values.

Reactions of Amino Groups

Ninhydrin reaction: detection of amino acids (purple color)
Sanger's reaction: N-terminal amino acid identification
Edman degradation: protein sequencing

Reactions of Carboxyl Groups

Esterification: protection during synthesis
Decarboxylation: formation of biogenic amines

Reactions of Side Chains

Specific reactions include disulfide bond formation in cysteine, oxidation, and various tests for detection and analysis.

Analytical Techniques for Amino Acids

Paper chromatography
Thin layer chromatography (TLC)
Ion exchange chromatography
High-performance liquid chromatography (HPLC)
Electrophoresis
Mass spectrometry

Functions of Individual Amino Acids

Each amino acid has unique roles, from structural components like collagen (Proline, Glycine) to neurotransmitter precursors (Tryptophan, Tyrosine) and metabolic intermediates.

Clinical Conditions Related to Amino Acid Metabolism

Disorder	Defect	Accumulated Compound	Symptoms
Phenylketonuria (PKU)	Phenylalanine hydroxylase deficiency	Phenylalanine	Mental retardation, fair skin, musty odor; treat with low-Phe diet
Alkaptonuria	Homogentisate 1,2-dioxygenase deficiency	Homogentisic acid	Black urine, ochronosis, arthritis
Maple Syrup Urine Disease (MSUD)	Branched-chain α-keto acid dehydrogenase deficiency	Leucine, Isoleucine, Valine	Urine smells like maple syrup, neurological deterioration

Neurotransmitter Synthesis from Amino Acids

Key pathways include glutamate to GABA, tryptophan to serotonin and melatonin, tyrosine to dopamine, norepinephrine, epinephrine, and thyroid hormones, and arginine to nitric oxide.

Amino Acid Pool and Metabolism Overview

The body maintains an amino acid pool (~100 g), sourced from diet, protein turnover, and synthesis. These amino acids are utilized for protein synthesis, nitrogenous compounds, energy, gluconeogenesis, ketogenesis, and urea formation.

Transamination: Key Reaction

Amino acids transfer their amino groups to α-ketoglutarate, forming glutamate and corresponding keto acids, catalyzed by transaminases such as ALT and AST.

Summary of Reactions and Tests

Reaction	Group Involved	Reagent	Product	Application
Ninhydrin reaction	-NH₂	Ninhydrin	Purple color	Detection of amino acids
Sanger's reaction	-NH₂	FDNB	DNP-amino acid	N-terminal identification
Edman degradation	-NH₂	PITC	PTH-amino acid	Protein sequencing

Visual Aids and Diagrams

For detailed structures and pathways, search Google Images for diagrams such as amino acid structures, titration curves, metabolic pathways, and reaction mechanisms to enhance understanding and exam preparation.

Nucleic Acids