Amino Acids PDF

Amino acids Tal Yardeni, PhD The central dogma Created with BioRender.com The common amino acids  Amino acids The first amino acid, asparagine, was discovered in 1806 by French chemists (Louis- Nicolas Vauquelin and Pierre Jean Robiq...

Amino acids Tal Yardeni, PhD The central dogma Created with BioRender.com The common amino acids  Amino acids The first amino acid, asparagine, was discovered in 1806 by French chemists (Louis- Nicolas Vauquelin and Pierre Jean Robiquet) Threonine is the last of the 20 common amino acids that was discovered (1935) by William Cumming Rose. William Cumming Rose also determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth. The names of some of the amino acid are derived from the source were they first isolated: Asparagine – asparagus Glutamate - Gluten Tyrosine – Greek tyros (cheese) Glycine – Glykos (sweet, because of its sweet taste)  Amino acids In 1902, Emil Fischer and Franz Hofmeister, proposed (independently) that proteins are formed from many amino acids There are correlations between amino acid sequences and the 3-D structures of proteins Functional correlations: The sequence of the amino acid can assign the protein to known families (e.g., secreted proteins, membrane protein, cytoplasmic protein, transcription factor, etc..) Similarity of amino acid sequences of the same protein in different species give critical information about evolutionary pathways Mutations and disease  Amino acids - Structure All 20 common amino acids shared the same structure: Amino group (NH3+) Carboxyl group (COO-) Hydrogen group R group All bonded to the same α-carbon atom The amino acids are different from each other in their R group. The R group is different by structure, size and electric charge. Therefore, its defines the characteristics of the amino acids which, define the structure and function of the protein.  Stereochemistry )‫(ארגון מרחבי של האטומים‬ The central atom is the chiral center The four groups can appear in two spatial compositions Amino acids have two possible stereoisomers Since they are non-superimposable mirror images of each other, they represent a class of stereoisomers called enantiomers The amino acid residues in proteins are almost all L stereoisomer. Only 1% are the D configurations.  Amino Acids are Amphoteric Can react either as acids or as bases, depending on circumstances: In aqueous acid solution, the carboxyl is a base - accepts a proton In aqueous base solution, the amino is an acid - loses a proton  The pH scale is indicates the activity of hydrogen (H+) ions in the solution pH 0-6 – Acidic pH 7- Neutral pH 8-14 -Basic pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa and titration curve pKa pKa and titration curve pKa  pKa and titration curve pH = 1 pH = 7 pH = 11  pKa and titration curve pKa values of carboxylic acid and α-amino groups are around 2.2 and 9.4, respectively Amino acids are dipolar ions At physiological pH, amino groups are protonated and carboxylic acid groups are unprotonated (in conjugate base form ,carboxylate) Dipolar ions = zwitterions bear charged groups of opposite polarity, net charge = 0  Isoelectric point The isoelectric point (pI), is the pH where the amino acid is without electrical charge Classification of amino acids by the R group Most useful classification by side chain polarity: Nonpolar R groups Uncharged polar R groups Charged polar R groups Structure of proteins depends on tendency for: Polar and ionic side chains to be hydrated Nonpolar side chains to associate with each other rather than with water therefore to be hydrophobic Disulfide Bond Formation: Oxidation of Two Thiols  Isoelectric point pH at which a molecule carries no net electric charge is its isoelectric point. For monoamino, monocarboxylic acids, like glycine pI = (pK1 + pK2)/2)  Isoelectric point for basic amino acids pI = (pKR + pK2)/2 for basic amino acids (lysine, arginine and histidine)  Isoelectric point for acidic amino acids pI = (pK1 + pKR)/2 for acidic amino acids (aspartate and glutamate)  Uncommon amino acids Amino acids that have been chemically modified after they have been incorporated into a protein ( posttranslational modification) Phosphorylation: Serin Threonine Tyrosine  Uncommon amino acids Amino acids that have been Hydroxylation: addition of OH. chemically modified after they Derivative of Proline: founds in have been incorporated into a collagen protein ( posttranslational modification)  Uncommon amino acids Amino acids that have been Carboxylation : addition of COO-. chemically modified after they Derivative of Glutamate: founds in have been incorporated into a prothrombin; blood clotting protein ( posttranslational modification)  Uncommon amino acids Amino acids that have been chemically modified after they have been incorporated into a protein ( posttranslational modification) Desmosine: derivative of 4 lysine residues and found in fibrous protein, elastin (protein found in connective tissue ).  Uncommon amino acids Ornithine and Citrulline are intermediates/ metabolites in the biosynthesis of Arginine and in the urea cycle. Non-proteinogenic amino acid.  Amino acid synthesis Essential amino acid are amino acids that cannot be synthesized from scratch by the organism and must come from the diet. Non-essential amino acid are amino acids that can be synthesized in sufficient quantities in the body. Conditionally essential amino acids are amino acids that usually not essential, except in times of illness and stress, such as prematurity in the infant or individuals in severe catabolic distress.  Amino acid synthesis While most bacteria and plants can synthesize all 20 amino acids, mammals can synthesize only half of them. All amino acids are derived from intermediates in glycolysis, citric acid cycle or the pentose phosphate pathway. Amino acid synthesis (Bacteria) Glycolysis is the process in which glucose is broken down to produce energy. Amino acids are synthesized from intermediates in the glycolysis network: 3-Phosphoglycerate: Serine, Glycine, Cysteine Phosphoenolpyrovate: Tryptophan, Phenylalanine, Tyrosine Pyruvate: Alanin, Valin, Leucine, Isoleucine Amino acid synthesis (Bacteria) Pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid: Ribose 5-phosphate: Histidine Erythrose 4-phosphate: Tryptophan, Phenylalanine, Tyrosine Amino acid synthesis (Bacteria) Citric acid cycle is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. Alpha-ketoglutarate: Glutamate, Glutamine, Proline, Arginine Oxaloacetate: Aspartate, Asparagine, Isoleucine, Methionine, Threonine, Lysine  Amino acid catabolism Amino acids can be acquired through the breakdown of intracellular or ingested dietary proteins. Amino acids can enter three metabolic routes within the body: Recycled to synthesize new proteins Combine with cofactors and substances to create amino acid derivatives Amino Acid Derivatives: Intermediates Some amino acids/derivatives can function as hormones or regulatory molecules: A. Neurotransmitters: GABA (glutamate decarboxylation product) and dopamine (a tyrosine derivative). B. Mediators of allergic reactions: histamine (histidine decarboxylation product). C. Hormone: Thyroxine (tyrosine derivative).  Amino acid catabolism Amino acids can be acquired through the breakdown of intracellular or ingested dietary proteins. Amino acids can enter three metabolic routes within the body: Recycled to synthesize new proteins Combine with cofactors and substances to create amino acid derivatives Catabolized into their functional groups and carbon skeletons. This process releases ammonium, which moves into the urea cycle and produces intermediates for energetic metabolic pathways Urea cycle  Metabolic disorders Phenylketonuria (PKU) Tyrosinemia Homocystinuria Maple syrup urine disease (MSUD)  Phenylketonuria (PKU) PKU is a genetic condition inherited from both parents, in which the body is unable to use one of the amino acid, phenylalanine (PHE). PHE is found in all protein foods such as meat, eggs, fish, milk and cheese and to a lesser extent in cereals, vegetables and fruits. In PKU, PHE can not be converted to TYR, and so PHE accumulates in the blood, this excess can retard physical and intellectual development.  Tyrosinemia Tyrosinemia is caused by a lack of the enzyme needed to metabolize tyrosine. The most common form of this disorder mostly affects the liver and the kidneys.  Homocystinuria Homocystinuria is a disorder of amino acid metabolism that is caused by a lack of the enzyme cystathionine beta-synthase, which is needed to metabolize the amino acid homocysteine. This disorder can cause a number of symptoms, including decreased vision, intellectual disability, and skeletal abnormalities.  Maple syrup urine disease (MSUD) Metabolic disorder affecting branched-chain amino acids (Leucine, Isoleucine and Valine). The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness.