Proteins PDF

 PROTEINS - In neutral solution, amino groups tend to accept - a naturally occurring, unbranched polymer in which protons (H+), producing a positively charged the monomer units are amino acids species. CHARACTERISTI...

 PROTEINS - In neutral solution, amino groups tend to accept - a naturally occurring, unbranched polymer in which protons (H+), producing a positively charged the monomer units are amino acids species. CHARACTERISTICS OF PROTEIN - Proteins are the most abundant substances in nearly - The net result is that in neutral solution, amino all cells next to water. acid molecules have the structure: - All proteins contain the elements carbon, hydrogen, oxygen, and nitrogen; most also contain sulfur. o Casein contains phosphorus. - A ZWITTERION is a molecule that has a o Hemoglobin contains iron. positive charge on one atom and a negative charge on another atom, but which has no net FUNCTIONS OF PROTEINS charge.  Enzymes o Low pH: acidic solution  Defense proteins o High pH: basic solution  Transport proteins - In an acidic solution, the —COO- zwitterion  Regulatory proteins accepts a proton (H+) to form a positively  Structural proteins charged ion.  Movement proteins  Nutrient proteins PROPERTIES OF AMINO ACIDS - In a basic solution, the —NH3+ of the zwitterion loses a proton, and a negatively 1. CHIRALITY OF AMINO ACIDS charged species is formed. - All amino acids are chiral, except GLYCINE. - This means that the structures of 19 of the 20 standard amino acids possess a CHIRAL CENTER at this location, so enantiomeric ABBREVIATIONS AND SYMBOLS FOR forms exist for each of these amino acids. COMMONLY OCCURING AMINO ACIDS o D-configuration: bacterial cell walls, antibiotics o L-configuration: all amino acids in proteins - Fischer Projection Formula for Amino Acids o The —COOH group is put at the top of the projection formula, the R group at the bottom. This positions the carbon chain vertically. o The —NH2 group is in a horizontal position. Positioning it on the left denotes the L isomer and positioning it on the right denotes the D isomer. 2. ACID-BASE PROPERTY OF AMINO ACIDS - Amino acids can have negative, zero, or positive charge depending on the pH of the aqueous environment. - In neutral solution, carboxyl groups tend to lose protons (H+), producing a negatively charged species.  o Major inhibitory neurotransmitter in the spinal cord o Precursor in the synthesis of heme, purine and creatine o α-helix breaker  ALANINE - R: —CH3 [methyl group] BASED ON POLARITY - Major gluconeogenic amino acid  NON-POLAR  Functions:  POLAR NEUTRAL o Can be converted to pyruvate by  POLAR ACIDIC transamination via ALT/SGPT  POLAR BASIC o Plays a role in the removal of Ammonia o Can be seen in cell walls of bacteria  NON-POLAR AMINO ACIDS - an amino acid that contains one amino group, one carboxyl group, and a nonpolar side chain Characteristics: o hydrophilic o generally found in the interior of proteins, where there is limited contact BRANCHED CHAIN AMINO with water ACIDS o no net charge - Branched Amino Acids o can be aromatic or aliphatic o Valine: —CH3CHCH3 [isopropyl group] o Leucine: —CH2CHCH3CH3 [isobutyl group] o Isoleucine: —CH3CHCH2CH3 [sec-butyl group]  Functions: o Alternative sources of energy - Maple Syrup Urine Disease [MSUD] o Defect of branched chain α-keto acid dehydrogenase o Inability to metabolize branched chain amino acids  GLYCINE - R: H  PROLINE - Simplest amino acid - R: aliphatic cyclic structure, - ONLY ACHIRAL AMINO ACID and the nitrogen is bonded to  Functions: two carbon atoms o Important component of collagen - ONLY IMINO ACID o Conjugated to bile acids, drugs and other - Function: α-helix breaker metabolites  - Sx: diarrhea, dermatitis, dementia, and possibly even death  METHIONINE - R: methylthioether group - Sulfur-containing amino acid  Functions: o Start codon: AUG  POLAR AMINO ACIDS o Involved in transfer of methyl groups as S-  3 types of polar amino acids have varying degrees adenosylmethionine (SAM) of affinity for water. - Norepinephrine → Epinephrine o Polar Neutral - Nortriptyline → Amitriptyline o Polar Acidic - Nordiazepam → Diazepam o Polar Basic o Precursor in the synthesis of homocysteine and - hydrophilic (“water-loving”) cysteine - often found on the surfaces of proteins  PHENYLALANINE - R: benzyl group - Aromatic amino acid - Most hydrophobic among the aromatic group  POLAR NEUTRAL AMINO ACIDS  Functions: - an amino acid that contains one amino group, o Converted to tyrosine via phenylalanine one carboxyl group, and a side chain that is polar but neutral hydroxylase - side chain: neither acidic nor basic o PHENYLKETONURIA: deficiency of - hydrophilic phenylalanine hydroxylase - no net charge - Sx: permanent intellectual disability, light skin and hair, seizures, developmental  TYROSINE delays, behavioral problems, and - R: phenyl ring psychiatric disorders - aromatic amino acid - CI: Aspartame, Phenylalanine  Functions: precursor of endogenous compounds - Treatment: remove Phenylalanine in diet o Catecholamines: DA, NE, EPI o Thyroid hormones: T3, T4 o Melanin: dark pigment found in the skin that serves as protection from excessive UV rays  SERINE AND THREONINE (ALCOHOLIC AMINO ACIDS) - R: hydroxyl groups - Serine: hydroxymethyl - Threonine: hydroxyethyl  TRYPTOPHAN  Function: site of phosphorylation of proteins - R: indole ring  CYSTEINE  Function: precursors of endogenous compounds - R: sulfhydryl group [—SH] o Serotonin: 5-hydroxytryptamine; regulation - Cysteine is a DIMER. of mood, cognition, vomiting reflex, - Two cysteine residues are linked via a covalent vasoconstriction disulfide bond o Melatonin: sleep-wake cycle in the pineal  Functions: gland o Participates in the biosynthesis of Coenzyme A o Vitamin B3 [Niacin] o Plays an important role in the stabilization of - Pellagra: deficiency of Vitamin B3 proteins   HISTADINE - R: imidazole ring - Only amino acid with near physiologic pH  Functions:  ASPARAGINE o Precursor of histamine - R: carboxamide [4-C]  Functions: o Precursor of aspartate o L-asparaginase: treatment of acute lymphocytic leukemia  ARGININE - R: guanidino group  GLUTAMINE  Functions: precursor of endogenous compounds - R: carboxamide [5-C] o Urea  Functions: o Nitric oxide o major Nitrogen carrier in the blood o Creatine Precursor of glutamate  POLAR ACIDIC AMINO ACIDS - an amino acid that contains one amino group and two carboxyl groups, the second carboxyl group being part of the side chain - side chain bears a negative charge BASED ON NUTRITIONAL REQUIREMENT  ASPARTIC ACID,  NON-ESSENTIAL ASPARTATE  ESSENTIAL - R: carboxyl groups [—  CONDITIONALLY ESSENTIAL COOH]  Functions:  NON-ESSENTIAL AMINO ACID o Previously used as a cardiac marker for - Non-essential amino acids can be synthesized in myocardial infarction the body o Converted to oxaloacetate via the enzymes - Dispensable amino acid AST/SGOT NON-ESSENTIAL AMINO ACIDS  GLUTAMIC ACID, Alanine GLUTAMATE Arginine - R: carboxyl group [—COOH] Asparagine  Function: major excitatory NT Aspartate Cysteine Glutamate Glutamine Glycine Proline Serine  POLAR BASIC AMINO ACIDS Tyrosine - an amino acid that contains two amino groups and one carboxyl group, the  CONDITIONALLY ESSENTIAL AMINO second amino group being part of the side ACIDS chain - amino acids that may be synthesized in the body - side chain bears a positive charge but not in adequate amounts or sufficient quantities - Examples: Arginine, Histidine  LYSINE - R: amino group [ε amino group] BASED ON METABOLIC FATE  Functions: precursor of L-carnitine  EXCLUSIVELY KETOGENIC  EXCLUSIVELY GLUHOGENIC  BOTH KETOGENIC AND GLUCOGENIC  EXCLUSIVELY GLUCOGENIC  OXYTOCIN - carbon skeletons are converted into pyruvate, 2- - regulates uterine contractions and lactation oxoglutarate, succinyl-CoA, fumarate, and - target tissues: uterus and breasts oxaloacetate and they act as glucose precursors - During delivery, stretching of the cervix of the - NOTE: All amino acids not classified as uterus stimulates the release of oxytocin which, in exclusively ketogenic or both ketogenic and turn, enhances contraction of smooth muscle cells glucogenic are exclusively glucogenic. in the wall of the uterus. - After delivery, it stimulates milk ejection (“let- EXCLUSIVELY KETOGENIC down”) from the mammary glands in response to Alanine Glutamate Glutamine the mechanical stimulus provided by a suckling Serine Histidine Arginine infant. Glycine Methionine Valine Cysteine Asparagine  VASOPRESSIN Aspartate Proline - regulates the excretion of water by the kidneys; it also affects blood pressure  EXCLUSIVELY GLUCOGENIC - another name: Antidiuretic Hormone (ADH) - carbon skeletons are catabolized to acetyl-CoA or - This name relates to vasopressin’s function in the acetoacetate and can therefore lead to production of kidneys, which is to decrease urine output in order fatty acids or ketone bodies to decrease water elimination from the body. Such - PURELY KETOGENIC AMINO ACIDS action is necessary when the body becomes o Leucine dehydrated. o Lysine  SMALL PEPTIDE NEUROTRANSMITTERS - ENKEPHALINS are pentapeptide neurotransmitters produced by the brain itself that bind at receptor sites in the brain to reduce pain. - Two best-known enkephalins: Met-enkephalin and Leu-enkephalin o Met-enkephalin: Tyr–Gly–Gly–Phe–Met o Leu-enkephalin: Tyr–Gly–Gly–Phe–Leu  SMALL PEPTIDES ANTIOXIDANTS - GLUTATHIONE (Glu–Cys–Gly) is present in  BOTH KETOGENIC AND GLUCOGENIC significant concentrations in most cells and is of - metabolism of some amino acids may lead to the considerable physiological importance as a formation of more than one metabolic intermediates regulator of oxidation–reduction reactions. of the Citric Acid Cycle - Specifically, glutathione functions as an antioxidant, protecting cellular contents from oxidizing agents such as peroxides and superoxides (highly reactive forms of oxygen often generated within the cell in response to bacterial invasion).  GENERAL STRUCTURAL CHARACTERISTICS OF PROTEINS BIOCHEMICALLY IMPORTANT SMALL - MONOMERIC PROTEIN is a protein in which PEPTIDES only one peptide chain is present.  HORMONES - MULTIMERIC PROTEIN is a protein in which  NEUROTRANSMITTERS more than one peptide chain is present.  ANTIOXIDANTS  Protein subunits: peptide chains present in multimeric proteins; may all identical to each  SMALL PEPTIDE HORMONES other or different kinds of subunits may be - Two best-known peptide hormones: OXYTOCIN present and VASOPRESSIN  Insulin: a multimeric protein with two protein - Each hormone is a nonapeptide (nine amino acid subunits residues) with six of the residues held in the form of o 21 amino acid residues a loop by a disulfide bond formed from the o 30 amino acid residues interaction of two cysteine residues.  BASED ON CHEMICAL COMPOSITION  ALPHA HELIX - SIMPLE PROTEIN is a protein in which only - a protein secondary structure in which a single amino acid residues are present. protein chain adopts a shape that resembles a coiled - CONJUGATED PROTEIN is a protein that has spring (helix), with the coil configuration one or more non-amino acid entities present in its maintained by hydrogen bonds structure in addition to one or more peptide chains.  Prosthetic group is a non-amino acid group present PROPERTIES OF ALPHA HELIX STRUCTURE in a conjugated protein. 1. The twist of the helix forms a right-handed, or clockwise, spiral. 2. The hydrogen bonds between C=O and N—H entities are orientated parallel to the axis of the helix. 3. A given hydrogen bond involves a C=O group of one amino acid and a N—H group of another amino acid located four amino acid residues further along the spiral. This is because one turn of the spiral includes 3.6 amino acid residues. 4. All of the amino acid R groups extend outward from the spiral. 5. There is not enough room for the R groups within the spiral. - Many α helices have predominantly hydrophobic R groups projecting from one side of the axis of the helix and predominantly hydrophilic R groups LEVELS OF PROTEIN STRUCTURE projecting from the other side. These amphipathic  PRIMARY STRUCTURE helices are well adapted to the formation of  SECONDARY STRUCTURE interfaces between polar and nonpolar regions such  TERTIARY STRUCTURE as the hydrophobic interior of a protein and its  QUARTERNARY STRUCTURE aqueous environment. - Alpha Helix Breakers  PRIMARY STRUCTURE o Glycine - order in which amino acids are linked together in a o Proline protein o Large R groups - order of attachment of the amino acids to each other o Charged R groups through peptide bonds - NOTE: The primary structure of a protein is the  BETA PLEATED SHEET SEQUENCE OF AMINO ACIDS in a protein - a protein secondary structure in which two fully chain—that is, the order in which the amino acids extended protein chain segments in the same or are connected to each other. different molecules are held together by hydrogen bonds  SECONDARY STRUCTURE - hydrogen bonding can be: - arrangement in space adopted by the backbone o INTERMOLECULAR (between two portion of a protein different chains) - two most common types of secondary structure: o INTRAMOLECULAR (a single chain o alpha helix (α helix) folding back on itself) o beta pleated sheet (β pleated sheet) - In molecules where the β pleated sheet involves a - type of interaction responsible for both of these single molecule, several U-turns in the protein chain types of secondary structure is hydrogen bonding arrangement are needed in order to form the between a carbonyl oxygen atom of a peptide structure. linkage and the hydrogen atom of an amino group of another peptide linkage farther along the protein backbone  SUPERSECONDARY STRUCTURE - Motifs: repetitive supersecondary structure - Characteristic combinations of a secondary structure 10 to 40 residues in length that recur in different proteins - They bridge the gap between the less specific regularity of a secondary structure and the highly specific folding of a tertiary structure. The same motif can perform similar functions in different proteins.  TERTIARY STRUCTURE - Overall three-dimensional shape of a protein that results from the interactions between amino acid side chains (R groups) that are widely separated from each other within a peptide chain CLASSIFICATION OF PROTEINS - A DOMAIN is a section of the protein structure  BASED ON SHAPE sufficient to perform a particular chemical or  BASED ON FUNCTION physical task such as binding of a substrate or other ligand. BASED ON SHAPE Most domains are modular in nature, that is,  FIBROUS PROTEIN contiguous in both primary sequence and three-  GLOBULAR PROTEIN dimensional space.  MEMBRANE PROTEIN Fibrous protein is a protein whose molecules have an elongated shape with one dimension much longer than the others. Globular protein is a protein whose molecules have  QUARTERNARY STRUCTURE peptide chains that are folded into spherical or globular - Quaternary protein structure is the organization among the various peptide chains in a multimeric shapes. Membrane protein is a protein that is found protein. - Most multimeric proteins contain an even number associated with a membrane system of a cell. of subunits (two subunits = a dimer, four subunits = a tetramer, and so on). The subunits are held together mainly by hydrophobic interactions between amino acid R groups. - The noncovalent interactions that contribute to tertiary structure (electrostatic interactions, hydrogen bonds, and hydrophobic interactions) are also responsible for the maintenance of quaternary structure. - The noncovalent interactions that contribute to quaternary structure are, however, more easily disrupted. - An example of a protein with quaternary structure is hemoglobin, the oxygen-carrying protein in blood. It is a tetramer in which there are two identical α chains and two identical β chains. Each chain enfolds a heme group, the site where oxygen binds to the protein.  FIBROUS PROTEIN VS. GLOBULAR PROTEINS PROPERTY FIBROUS GLOBULAR PROTEINS PROTEINS Solubility Water-insoluble Dissolves in water Structure a single type of often contain secondary several types of structure secondary structure Function structural involved in functions that metabolic provide support chemistry,  HEMOGLOBIN and external performing - transports oxygen from the lungs to tissue protection functions such a tetramer (four peptide chains) with each subunit as catalysis, also containing a heme group, the entity that binds transport, and oxygen regulation - with four heme groups present, a hemoglobin molecule can transport four oxygen molecules at the  KERATIN same time. - Particularly abundant in nature, where it is found in - Iron atom: at the center of the heme molecule that protective coatings for organisms actually interacts with the O2 - Major protein constituent of hair, feathers, wool, fingernails and toenails, claws, scales, horns, turtle  MYOGLOBIN shells, quills, and hooves - Functions as an oxygen storage molecule in muscles - Introduction of disulfide bridges within the several - MONOMER: a single peptide chain and a heme levels of coiling structure determines the unit “hardness” of an α keratin - Myoglobin has a higher affinity for oxygen than - “Hard” keratins, such as those found in horns and does hemoglobin. nails, have considerably more disulfide bridges than - Thus, the transfer of oxygen from hemoglobin to their softer counterparts found in hair, wool, and myoglobin occurs readily. Oxygen stored in feathers myoglobin molecules serves as a reserve oxygen source for working muscles when their demand for oxygen exceeds that which can be supplied by hemoglobin. MYOGLOBIN VS. HEMOGLOBIN MYGLOBIN HEMOGLOBIN Monomeric protein Tetrameric protein Single peptide chain α2β2  COLLAGEN 1 heme unit 4 polypeptide chains - most abundant of all proteins in humans (30% of 4 heme units total body protein), is a major structural material in Binds to single oxygen Binds to four oxygen tendons, ligaments, blood vessels, and skin; it is molecule molecules also the organic component of bones and teeth Oxygen storage Oxygen transport - predominant structural feature within collagen Non-cooperative binding Cooperative binding molecules is a triple helix formed when three chains of amino acids wrap around each other to give a BASED ON FUNCTION ropelike arrangement of polypeptide chains 1. Catalytic proteins. Proteins are probably best known for their role as catalysts. Proteins with the role of biochemical catalyst are called enzymes. 2. Defense proteins. These proteins, also called immunoglobulins or antibodies, are central to the functioning of the body’s immune system. 3. Transport proteins. These proteins bind to particular small biomolecules and transport them to other locations in the body and then release the small molecules as needed at the destination  location. E.g., hemoglobin, transferrin, LDL and  IMMUNOGLOBULINS HDL - a glycoprotein produced by an organism as a protective response to the invasion of 4. Messenger proteins. These proteins transmit microorganisms or foreign molecules signals to coordinate biochemical processes - serve as antibodies to combat invasion of the body between different cells, tissues, and organs. E.g., by antigens insulin, glucagon, human growth hormone o Antigen: a foreign substance, such as a bacterium or virus, that invades the human 5. Contractile proteins. These proteins are necessary body for all forms of movement. Muscles are composed o Antibody: a biochemical molecule that of filament-like contractile proteins that, in counteracts a specific antigen response to nerve stimuli, undergo conformation changes that involve contraction and extension. E.g., actin and myosin, long flagella of sperm 6. Structural proteins. These proteins confer stiffness and rigidity to otherwise fluid-like biochemical systems. Collagen is a component of cartilage, and a keratin gives mechanical strength as - The importance of immunoglobulins is amply and well as protective covering to hair, fingernails, tragically demonstrated by the effects of AIDS feathers, hooves, and some animal shells. (acquired immunodeficiency syndrome). The AIDS virus upsets the body’s normal production of 7. Transmembrane proteins. These proteins, which immunoglobulins and leaves the body susceptible span a cell membrane, help control the movement to what would otherwise not be debilitating and of small molecules and ions through the cell deadly infections. membrane. Many such proteins have channels - CD4 cells (also known as CD4+ T cells) are white through which molecules can enter and exit a cell. blood cells that fight infection. CD4 cell count is an Such protein channels are very selective, often indicator of immune function in patients living with allowing passage of just one type of molecule or HIV and one of the key determinants for the need of ion. opportunistic infection (OI) prophylaxis. CD4 cell counts are obtained from bloodwork as part of 8. Storage proteins. These proteins bind (and store) laboratory monitoring for HIV infection. small molecules for future use. E.g., ferritin, myoglobin  PROTEIN HYDROLYSIS AND DENATURATION 9. Regulatory proteins. These proteins are often - When a protein or smaller peptide in a solution of found “embedded” in the exterior surface of cell strong acid or strong base is heated, the peptide membranes. They act as sites at which messenger bonds of the amino acid chain are hydrolyzed, and molecules, including messenger proteins such as free amino acids are produced. insulin, can bind and thereby initiate the effect that - Protein digestion is simply enzyme-catalyzed the messenger “carries.” Regulatory proteins are hydrolysis of ingested protein. often the molecules that bind to enzymes (catalytic The hydrolysis of cellular proteins to amino acids is proteins), thereby turning them “on” and “off” and an ongoing process, as the body resynthesizes thus controlling enzymatic action. needed molecules and tissue. 10. Nutrient proteins. These proteins are particularly important in the early stages of life, from embryo to infant. Casein, found in milk, and ovalbumin, found in egg white, are two examples of such proteins.  PROTEIN DENATURATION - Partial or complete disorganization of a protein’s 11. Buffer proteins. These proteins are part of the characteristic three-dimensional shape as a result of system by which the acid-base balance within body disruption of its secondary, tertiary, and quaternary fluids is maintained. structural interactions. - Protein denaturation does not affect the primary 12. Fluid-balance proteins. These proteins help structure of a protein. maintain fluid balance between blood and - Often, for limited denaturation changes, it is surrounding tissue. Two well-known fluid-balance possible to find conditions under which the effects proteins, found in the capillary beds of the of denaturation can be reversed; this restoration circulatory system, are albumin and globulin. process, in which the protein is “refolded,” is called renaturation.  Denaturing Agents Interaction Heat Disrupts H-bonding, hydrophobic interactions, often irreversible Extreme pH Disrupts ionic interaction Organic solvents or Disrupts hydrophobic detergents interactions Mercaptoethanol Disrupts disulfide bonds Heavy metal salts Disrupts disulfide bonds