Amino Acid Chemistry.pdf

Amino Acid Chemistry: An Introduction Foundation - I Module Johar Iqbal Faculty of Medicine 2024-2025  Organism Human Being, other organisms Orga...

Amino Acid Chemistry: An Introduction Foundation - I Module Johar Iqbal Faculty of Medicine 2024-2025  Organism Human Being, other organisms Organ Systems Cardiovascular System Organs Heart, Artery, Vein Tissues Connective tissue Cells Cardiac Myocyte Glycoproteins, Lipoproteins, Biomolecules Proteoglycans, Glycolipid, Nucleoproteins Carbohydrates Proteins Lipids Nucleic Acids Organism: At molecular level an organism is made up of four basic biomolecules Protein Protein Amino Acids  Objectives Define amino acids, their structure Properties of amino acids – Asymmetry – Amphoteric – Isoelectric pH [Isoelectric point (pI)], Zwitterion Classification: Amino Acids Nitrogen Balance Derivatives of Amino Acids  General Overview Over 300 naturally occurring amino acids 20 proteinogenic amino acids Biosynthesis of Purine, Porphyrin, Pyrimidine and urea Role in nerve transmission and hormone synthesis  Amino Acid All amino acids of physiological significance in human body, posses L-α configuration Structure of Amino Acids  Asymmetry (Chirality) All amino acids are chiral except Glycine  Amphoteric Properties of Amino Acids Amphoteric substances act as acids or bases. – They are acids when they donate protons. – They are bases when they accept protons. Amino acids can act as acids or bases. – When placed in an acidic solution (low pH), they act as bases by accepting protons and becoming positively charged. – In basic solutions (high pH), they act as acids by donating protons and becoming negatively charged.  ALANINE CH3 O - + + NH3 CH C - O H+ OH- Acid Basic Solution Solution CH3 O CH3 O + NH2 CH C - NH3 CH C O OH NET CHARGE NET CHARGE +1 -1  Amino Acids function as buffers (discussed in the coming tutorial) because they can neutralize small increases of acid or base. Proteins are one of the major buffering systems in the body. Histidine has maximum buffering capacity due to the imidazole group  Amino Acid exist as Zwitterion Any molecule containing equal amount of positively and negatively charged functional groups, simultaneously, is known as Zwitterion.  ISOELECTRIC POINT (pI) A Zwitterion, which is electrically neutral overall, can only exist at a specific pH value. This pH value, called the isoelectric point, is different for each amino acid. Amino acids with hydrocarbon R groups attain their isoelectric point between pH 5.0 and 7.0 ex. Leucine pH = 6.0 Basic amino acids need high pH values to reach their isoelectric points. ex. Arginine pH = 10.8  Acidic amino acids need low pH values. ex. Aspartic acid pH = 3.0 Proteins also have isoelectric points depending on the amino acids that make them up. – At their pI, proteins become insoluble in the solution, clump together, and precipitate out of the solution.  Classification of Amino Acids Based on the type and nature of the ‘R’ group ØIt is the properties of the R group that determine the property of the amino acid and ultimately the protein ØIt also defines the hydrophobicity, polarity and charges on amino acids Based on polarity (Water solubility) Based on the essentiality in diet Based on fate, i.e., gluconeogenic/ketogenic capacity  AMINO ACIDS Acidic or their Aliphatic Hydroxyl Sulfur amides Glycine (Simplest) Aspartate Serine Alanine BCAA* Cysteine Asparagine Threonine Valine (Val) Valine Methionine Glutamate Tyrosine Leucine (Leu) Leucine Glutamine Isoleucine (Iso) Isoleucine Basic Aromatic Imino Arginine (Guanidino gp) Tyrosine Histidine (Imidazole gp) Tryptophan (Indole gp) Proline Lysine (ε-amino) Phenylalanine *BCAA – Branched Chain Amino Acid  AMINO ACIDS POLAR NON-POLAR Uncharged Acidic Basic Valine Alanine Leucine Isoleucine Glycine Phenylalanine Serine Tryptophan Lysine Proline Threonine Aspartate Histidine Methionine Asparagine Glutamate Arginine Tyrosine Glutamine Cysteine  Hydrophobic (Non-Polar) Amino Acid Proteins folding occurs in a manner that amino acid with hydrophobic side chains are in the interior (core) of the molecule and those with hydrophilic side chains are on the surface (periphery).  Hydrophobic (Non-Polar) Amino Acid Valine, leucine and isoleucine are branched-chain amino acids whose metabolism is abnormal in maple syrup urine disease. Proline is a secondary amine whose presence in a protein disrupts normal secondary structures. Sickle cell anemia, a sickling disease of red blood cells, results from the substitution of polar glutamate by nonpolar valine at the sixth position in the β subunit of hemoglobin Methionine, another sulfur-containing amino acid, is a part of S-adenosylmethionine (SAM), a methyl donor in biochemical pathways  Hydrophilic (Polar) Amino Acid Serine and threonine are sites for O-linked glycosylation of proteins, a post-translational modification that should be associated with the golgi bodies Asparagine is a site for N-linked glycosylation of proteins, a post-translational modification that should be associated with the endoplasmic reticulum Cysteine contains sulfur and can form disulfide bonds to stabilize the shape (tertiary structure) of protein. Destroying disulfide bonds denatures proteins.  Nitrogen Balance Nitrogen balance is the normal condition in which the amount of nitrogen incorporated into the body each day exactly equals the amount excreted. Nitrogen intake = Nitrogen excreted  Negative Nitrogen Positive Nitrogen Balance occurs when Balance occurs when the nitrogen loss exceeds the amount of nitrogen intake intake exceeds the amount excreted Intake < Excretion Intake > Excretion Causes Causes – Protein Malnutrition – Growth (Kwashiorkor) – Pregnancy – Dietary deficiency of even – Recovery phase of injury or one essential amino acid surgery – Starvation – Recovery from conditions – Uncontrolled Diabetes associated with negative nitrogen balance – Infection  Based on dietary essential Essential Amino Acids Arginine and histidine are vPhenylalanine (P) semi-essential amino acids vValine (V) (essential only during periods of positive nitrogen vThreonine (T) balance). vTryptophan (T) vIsoleucine (I) Complete or Adequate vMethionine (M) Proteins: supply all of the vHistidine (H) essential amino acids. (Animal Proteins) vArginine (A) Incomplete Proteins: Low in vLeucine (L) one or more of the essential vLysine (L) amino acids (Vegetable PVT. TIM HALL always argues, never tires Proteins) Gluconeogenic/ Ketogenic  21st amino Acid Selenocysteine  Amino Acid Derivatives Important Derivative Tryptophan: Serotonin, Melatonin, Niacin Tyrosine: Dopamine, Norepinephrine, Epinephrine Histidine: Histamine Derivatives Amino Acids Nitric Oxide Arginine is the precursor Spermine Synthesized from Ornithine It is formed by decarboxylation of L- GABA (Gamma- glutamate, a reaction catalyzed by L- aminobutyric acid) glutamate decarboxylase. It is the chief inhibitory neurotransmitter in the brain.  Q1-Which of the following amino acids is non-polar? A. Lysine B. Serine C. Leucine D. Threonine  Q2-Which of the following amino acids is more likely to a have pI