Amino Acids & Proteins Part 1 PDF

Cellular Biology & Homeostasis AMINO ACIDS & PROTEINS Part 1 VP 2024 Clara Camargo, DVM Learning Objectives 1. Understand the general structure of the amino acids and proteins 2. Explain the importance of the amino acid side chains and how it influence the amino acid physicochemical characteristics...

Cellular Biology & Homeostasis AMINO ACIDS & PROTEINS Part 1 VP 2024 Clara Camargo, DVM Learning Objectives 1. Understand the general structure of the amino acids and proteins 2. Explain the importance of the amino acid side chains and how it influence the amino acid physicochemical characteristics 3. List and briefly describe the amino acids derivatives, peptides and polypeptides and list their physiological relevance 4. Describe the digestion and absorption of dietary proteins in monogastric. Compare it with the digestion and absorption of carbohydrates and lipids 5. Describe the amino acids catabolism TERMINOLOGY/ABBREVIATONS Acidic Peptides Amino acids Physiological pH Amino group Polar amino acid Antibody Polypeptides Basic Proteinogenic amino acid Carboxyl group Proteins Contractile proteins Splicing Glucogenic amino acid Standard amino acid Ketogenic amino acid Structural proteins Metabolic proteins Transcription Nonpolar amino acid Translation Oligopeptides Transport proteins Peptide bond AMINO ACIDS (AA) & PROTEINS CH₃(CH₂)nCOOH RCH(NH₂)nCOOH Protein structure https://www.youtube.com/watch?v=Q7dxi4ob2O4 (CH₂O)n From: Silbernagl. Color Atlas of Physiology AMINO ACIDS & PROTEINS – Central Dogma of molecular biology Chemical structure of DNA https://youtu.be/7vMaAQ6zb7g DNA replication https://youtu.be/oCFN5WUoLRI How DNA is packed https://youtu.be/ttu3sCFpp-M DNA transcription https://youtu.be/-AnsJILjbz8 Translation https://youtu.be/tTlZQQtoq5Q From: Silbernagl. Color Atlas of Physiology Proteins are the products of our genes  Central dogma of molecular biology: DNA → RNA → Protein Transcription → Splicing → Translation Nucleus Ribosome Endo. Retic Golgi App Vesicles What Organelles are involved in protein synthesis? AMINO ACIDS & PROTEINS - Function Proteins are:  The most abundant & functionally diverse molecules in living systems  ALL physiological processes depend on these molecules  Diverse, and share fundamental common structural function of being linear polymers of AA’s Category Examples Function Metabolic Proteins Enzymes & Peptide Hormones Direct and Regulate Metabolism Contractile Proteins Actin & Myosin Permit Movement Structural Proteins Collagen & Keratin Form tissues & bones Transport Proteins Albumin & Hemoglobulin Move essential molecules thru bloodstream Antibody Immunoglobulins Fight infections ( Viruses, Bacteria etc) AMINO ACIDS & PROTEINS - Function Transport Proteins Channels Enzymes Membrane Proteins Signal Proteins Hormone Receptors Second Messengers Structure Proteins AA, PEPTIDES, POLYPEPTIDES and PROTEINS Protein  Biologically occurring sequencing of amino acid (AA) monomers linked by peptide bonds  Formed when the carboxyl group of 1 AA reacts with the amino group of another AA Peptides are distinguished from proteins based on the size of the chain  Shortest peptides are dipeptides. tripeptides, tetrapeptides…  Peptides → 50 or fewer amino acids  Oligopeptides: 2-20 AA  Polypeptides: 21-50 AA (long, continuous unbranched peptide chain) AA → Peptides → Proteins PEPTIDE BOND - Condensation Reaction Condensation reaction: It is NOT a spontaneous reaction ATP dependent AMINO ACIDS (AA’s) Only ~ 20 commonly seen in mammalian proteins AA structure determines how they interact with each other > 300 in nature AA are composed of: 1.An Amino Group 2.An Acid (Carboxyl Group) 3.A distinct side chain (R-Group) bonded to the α-carbon  Side chain determines role of AA in the protein Proteinogenic AA Standard amino acids encoded by DNA Nonstandard amino acids are synthesized by chemical modification of standard amino acids Selenocysteine: 21st proteinogenic AA (coded by a “STOP” codon). THE 20 STANDARD AMINO ACIDS Special case Special case Special case THE 20 STANDARD AMINO ACIDS In proteins, most carboxyl and amino groups of amino acids are combined through peptide bonds Therefore, these groups are not available for chemical reactions Thus, the chemical nature of the side chain determines the role that the amino acid plays in a protein The side (R-)chain distinguishes 1 AA from another AA  R-group can be polar, nonpolar, negatively charged, or positively charged) Particularly how the protein folds into its native conformation AMINO ACIDS NON-POLAR SIDE CHAINS Each have a nonpolar side chain that does not gain or lose protons or participate in hydrogen or ionic bonds The side chains of these amino acids can be regarded as ‘oily’ or lipid-like, which promotes hydrophobic interactions In proteins found in aqueous solution, the side chains tend to cluster together in the interior of the protein (hydrophobic effect) Glycine: no side chain! Only H atom AMINO ACIDS - Proline Differs from other nonpolar amino acids: side chain & alpha-amino nitrogen form a rigid, five-membered ring structure Secondary instead of Primary amino group (called imino group) Unique geometry of proline: Imino group  Formation of the fibrous structure (i.e.; Collagen)  Interrupts the α-helices in globular proteins From: Harvey and Ferrier. Biochemistry AMINO ACIDS Uncharged Polar Side Chains AA with Uncharged Polar Side Chains Have zero net charge at physiologic pH Serine, threonine, & tyrosine o Have a polar hydroxyl group: Participate in H+ bond formation Asparagine & glutamine side chain o Contain carbonyl group & an amine group, o Can also participate in hydrogen bonds Side chain of cysteine contains a sulfhydryl group (thiol, -SH group) o Important for disulfide bonds formation between proteins Cysteine and tyrosine side chain can lose a proton at an alkaline pH Cysteine: -SH bond is slightly polarized, but it‘s overall behaves as a nonpolar molecule AMINO ACIDS Charged - Acidic side chain AA with Polar Acidic Side Chains Proton donors  Aspartic Acid and Glutamic Acid Glutamic acid At physiological pH the side chains are: Fully ionized and negatively charged From: Harvey and Ferrier. Biochemistry aspartate and glutamate → negative charge of amino acid molecule Glutamic acid → glutamate Aspartate AMINO ACIDS Charged – Basic side chain Proton acceptors At physiological pH the side chains are: Fully ionized and positively charged  Histidine‘s side chain:  Can be either (+) charged or Neutral  depending on the environment‘s pH  Important function as buffer NON-POLAR AMINO ACIDS AND POLAR AMINO ACIDS Location of nonpolar amino acids in soluble protein and membrane protein AMINO ACIDS DERIVATIVES Tyrosine:  Triiodothyronine (T3) & thyroxine (T₄) → thyroid hormones  Dopamine Taurine:  Bile acids Glutamate:  GABA → is an inhibitory neurotransmitter Tryptophan:  Serotonin → neurotransmitter, plays key role in digestion, mood, sleep, healing... Histidine:  Histamine → mediator of allergic reactions Lysine:  Carnitine → lipid oxidation AMINO ACIDS FYI DERIVATIVES Synthesis of important neurotransmitters: Hydroxylation of tyrosine yields: L-DOPA- >decarboxylated to form the neurotransmitter dopamine In some neurons dopamine is hydroxylated to form norepinephrine PEPTIDES with physiological relevance Oxytocin: peptide hormone (9 AA peptide) produced in the hypothalamus (uterine contractions and milk secretion) Antidiuretic hormone (ADH): 9 peptide produced in the hypothalamus and essential for maintenance of water balance Creatine: tripeptide involved in energy production in muscle and cardiac cells Bradykinin: 9 peptide, vasoactive substance Angiotensin II, 10 pep, a potent vasoconstrictor Melanin: tripeptide, a pigment occurring in several tissues, synthesized from tyrosine via DOPA POLYPEPTIDES with physiological relevance Gastrin Glucagon o Stomach hormone o Produced by α-cells of the pancreas o Stimulates secretion of gastric glands o Stimulates glycogenolysis CCK (cholecystokinin) o Stimulates pancreas and liver secretion (i.e.; bile from gall bladder) Atrial Natriuretic Peptide (ANP): o Produced in the heart (atrium) o Essential for regulation of blood volume and pressure PROTEIN DIGESTION and AA METABOLISM Unlike fats and carbohydrates, AA are not stored by the body o No protein exists just for storage of amino acids They must be: o Obtained from the diet (9 AA are essential) o Released through the degradation of body protein o De novo synthesis (from intermediate metabolites) PROTEIN DIGESTION – Dietary protein Starts in the stomach → gastric juice (HCl and pepsinogen) Protein Digestion Enzymes of luminal-phase digestion  Gastrin stimulates HCL and pepsinogen secretion  HCl → kills bacteria and denature protein (facilitates enzymatic hydrolysis)  Pepsinogen is activated → pepsin → protein hydrolysis Continues in the small intestine by pancreatic enzymes Cunningham’s Textbook of Veterinary Physiology Veterinary Physiological Chemistry Protein Digestion PROTEIN DIGESTION and ABSORPTION Membranous-phase digestion Enterocyte (brush border) absorption:  peptidases  amino acids, dipeptides and tripeptides Cunningham’s Textbook of Veterinary Physiology Cunningham’s Textbook of Veterinary Physiology Protein Digestion PROTEIN DIGESTION – Fate of dietary AA after absorption Most amino acids are removed by the liver on “First Pass” (Hepatic Portal Circulation), never reaching the systemic circulation. Liver helps keep blood amino acid concentrations stable during periods of amino acid absorption. The blood amino acid concentration, as with the blood glucose concentration, is usually kept relatively constant. AA are used in the liver for protein synthesis and energy production. During the absorptive period, amino acids for peripheral (non hepatic) protein synthesis must come from that portion of amino acids that escape hepatic catabolism. AA METABOLISM (green) AA METABOLISM - DEGRADATION In liver  AA catabolism  into ammonia (NH3)/urea (amine part of AA) and α-keto acids (the carbon skeletons of AA) The carbon skeletons of the α-keto acids are converted to common intermediates of energy-producing metabolic pathways  Which can be metabolized by central pathways of metabolism All AA’s in excess of biosynthetic needs are rapidly degraded → AA are not stored! (i.e.; gluconeogenesis, glycolysis, TCA cycle) to:  CO2 and H2O  Glucose, fatty acids, or ketone bodies AA METABOLISM - DEGRADATION Little free ammonia is excreted in urine, most is used in synthesis of urea  Urea cycle  Most important route for disposing of nitrogen from the body  Urea is excreted by the kidneys in urine “ NOTHING IS LOST, NOTHING IS CREATED, EVERYTHING IS TRANSFORMED Antoine Lavoisier ”