UNIT 2: Proteins PDF

PINES CITY COLLEGES COLLEGE OF PHARMACY Magsaysay Avenue, Baguio City 2600 Tel. No. (074) 445-2210 Loc. 51 Fax : (074) 445-2208...

PINES CITY COLLEGES COLLEGE OF PHARMACY Magsaysay Avenue, Baguio City 2600 Tel. No. (074) 445-2210 Loc. 51 Fax : (074) 445-2208 www.pcc.edu.ph UNIT 2: PROTEINS I. Introduction to Amino Acids - Building blocks of proteins→ chemical properties determine the biologic activity of the protein - Dictates the growth, repair, and maintenance of all cells II. Structure - Contains at least one of both amino and carboxylic functional groups The N-terminal end amino group and the C-terminal end carboxyl group bond to the α-carbon, with the amino group of one amino acid linking with the carboxyl group of another, forming a peptide bond - Amphoteric in nature since it possess both basic and acidic group - Zwitterion is a form of amino acid that has both positive and a negative charge but has no net charge - Polypeptide: a chain of amino acids - In human serum, proteins average about 100-150 amino acids in polypeptide chains. Amino acids differ from one another by the chemical composition of their R-group - Classifications of amino acids 1. According to structure 2. According to Polarity 3. According to Metabolic Fate 4. Nutritional Classification III. Essential Amino Acids 1. Arginine (Arg) - Complex amino acid often found at the catalytic site in proteins and enzymes due to its amine-containing side chain - Uses a. Used in cell division, wound healing, protein synthesis stimulation, immune function, and hormone release b. Increases the size and activity of the thymus gland, which manufactures T lymphocytes Prepared by: Giana Grace Manuel, RPh 1  c. Required for the generation of urea → necessary for the removal of toxic Ammonia from the body d. Good for liver disorders such as cirrhosis of the liver and fatty liver e. Required for the synthesis of creatine → Degrades to creatinine 2. Histidine (His) - Basic amino acid due to its Imidazole side chain - Uses a. Direct precursor of histamine b. Important source of carbon atoms in the synthesis of C in purine c. Growth and repair of tissues and maintenance of myelin sheaths that protect nerve cells d. Manufacture of red and white blood cells e. Protection of the body from heavy metal toxicity f. ⬆Levels: stress and psychological disorders like anxiety and schizophrenia g. ⬇Levels: contribute to rheumatoud arthritis and may be associated with nerve deafness 3. Isoleucine (Ile) - Branched-chain amino acid - Uses a. Helps maintain, heal, and repair tissue, skin, and bones b. Helps regulate blood glucose levels and maintain energy levels 4. Leucine (Leu) - Branched chain amino acid - Uses a. Boosts the healing of muscle, skin, and bones in conjunction with valine and isoleucine b. Lowers blood glucose and acids in increasing growth hormone production c. Necessary for the optimal growth of infants and for nitrogen balance in adults 5. Lysine (Lys) - Has a net positive charge which makes it one of the three basic amino acids - Uses a. Needed for proper growth and bone development in children b. Maintains proper nitrogen balance in adults c. Plays a role in the production of antibodies and lowers triglyceride levels (lipids) d. Helps in the absorption and conservation of calcium and plays an important role in the formation of Collagen 6. Methionine (Met) - Uses a. Helps initiate the translation of messenger RNA (mRNA) by being the first amino acid to be incorporated into the N-terminal position of all proteins b. Intermediate biosynthesis of cysteine, lecithin and taurine c. Source of sulfur, required by the body for normal metabolism and growth d. Assists the breakdown of fats Prepared by: Giana Grace Manuel, RPh 2  e. Helps diminish muscle weakness, prevents brittle hair f. Helps to detoxify lead and other heavy metals g. Reacts with adenosine triphosphate to contribute to the synthesis ofmany important substances, including epinephrine and choline 7. Phenylalanine (Phe) - Has a benzyl side chain which contributes to its hydrophobic nature - Uses a. Promotes alertness and vitality, elevates mood, decreases pain, aids memory and learning, and is used to treat arthritis and depression b. Used by the brain to produce norepinephrine c. Interferes with the production of serotonin, another neurotransmitter in large quantities d. Used as an antidepressant and analgesic e. Uses an active transport channel to cross the blood brain barrier f. Plays a key role in the biosynthesis of other amino acids g. Part of the composition of aspartame 8. Threonine (Thr) - Alcohol containing amino acid - Uses a. Important in the formation of protein, collagen, elastin, and tooth enamel b. Maintain proper protein balance in the body and aids liver function, metabolism, and assimilation c. Important in the production of neurotransmitters and health of nervous system 9. Tryptophan (Trp) - Aromatic amino acid - Formed from proteins during digestion by the action of proteolytic enzymes - Uses a. Precursor for serotonin and melatonin, a neurohormone and powerful antioxidant b. Precursor of Niacin c. Natural relaxant, helps alleviate insomnia by indusingsleep, soothes anxiety, and reduces depression d. Used in the treatment of migraine headaches, aids in weight control by reducing appetite, and helps control hyperactivity in children e. Adequate amount of Pyridoxine is necessary for formation of tryptophan, which in turn is required for the formation of serotonin 10. Valine (Val) - Branched chain amino acid - Uses a. Needed for muscle metabolism and coordination, tissue repair, and maintenance of nitrogen balance b. Used by muscke tissue as an energy source Prepared by: Giana Grace Manuel, RPh 3  c. Used in the treatments for muscle, mental, and emotional problems, anxiety, liver and gallbladder disease IV. Non-Esssential Amino Acids 1. Alanine (Ala) - One of the simplest of the amino acids - Product of breakdown of DNA or the dipeptides, anserine and carnosine, and the conversion of pyruvate, a pivotal compound in carbohydrate metabolism - Uses a. Strengthens the immune system through the production of antibodies b. Beta alanine is a constituent of pantothenic acid and coenzyme A c. Aids in metabolism of glucose d. Helps in reducing the buildup of toxic substances that are released into muscles cells when muscle protein is broken down quickly to meet aenergy needs e. Plays a major role in the transfer of nitrogen from peripheral tissue to the liver 2. Asparagine (Asn) - First amino acid to be isolated in 1806 - One of the principal and the most abundant of the amino acids involved in the transport of nitrogen - Β-amide of aspartic acid synthesized from aspartic acid and ATP - Uses a. Maintains balance in the CNS b. Converts one amino acid into another via amination and transamination c. Required by the Nervous System and plays an important role in the synthesis of Ammonia 3. Aspartic Acid (Asp) - Alanine with one of the β-hydrogens replaced by a carboxylic acid group - Uses a. Plays a vital role in metabolism during cinstruction of other amino acids and metabolites in the citric acid cycle b. A metabolite in the urea cycle and participates in gluconeogenesis, the generation of glucose from non- sugar carbon substances c. Helps to protect the liver by aiding in the removal of excess ammonia d. Enhances the production of immunoglobulins 4. Cysteine (Cys) - With sulfhydryl group - Named after cystine, its oxidized dimer - Important structural and functional component of many proteins and enzymes - Precursor to glutathione - Potentially toxic and is catabolized in the GIT and blood - Absorbed during digestion as cystine, which is more stable in the GIT - Uses a. As a constituent in the food, pharmaceutical and personal care industries Prepared by: Giana Grace Manuel, RPh 4  b. Production of flavors c. N-acetylcysteine 5. Glutamic Acid (Glu) - Synthesized from a number of amino acids, and when an amino group is added to glutamic acid, it forms the important amino acid glutamine - One of the two amino acids that have a net negative charge making it very polar molecule - Uses a. Aids in cognitive functions, such as learning and memory b. Important in the metabolism of fats and sugars c. Aids in transporting potassium into the spinal fluid (BBB) d. Serves as neurotransmitters and dysregulation has been linked to epileptic seizures e. Brain fuel f. Present in a wide variety of foods and is responsible for one of the five tastes of human sense of taste 6. Glutamine(Gln) - Most abundant amino acid in the body - Involved in more metabolic processes than any other amino acid - Uses a. Brain fuel b. Provides fuel for a healthy digestive tract c. Assists in maintaining the proper acid/alkaline balance in the body d. Converted to glucose when more glucose is required for energy and aids in immune function e. Basis of the building blocks for the synthesis of RNA and DNA f. Transports ammonia to the liver, where it is converted into less toxic urea and then excreted by the kidneys g. Used in the treatment of serious illnesses, injury, trauma, burns, and cancer treatment-related side effects and in wound healing for post operative patients 7. Glycine (Gly) - Simplest amino acid synthesized in the body - Only amino acid that is not optically active because it has no streoisomers - Uses a. Used by the liver to to help in the detoxification of compounds and to help in the synthesis of bile acids b. Major inhibitory neurotransmitters in the CNS, especially in the spinal cord, brainstem and retina c. Synthesis of heme d. Essential for the synthesis of nucleic acids, proteins, peptides, purines, ATP, porphyrins, glutathione, creatine, bile salts, glucose, glycogen, and other amino acids e. Found in the skin and connective tissues, it is useful for repairing damaged tissues and promoted healing f. Metal complexing agent g. Improves glycogen storage h. Retards muscle degeneration Prepared by: Giana Grace Manuel, RPh 5  8. Proline (Pro) - Precursor of hydroxyproline which is manufactured into collagen, tendons, ligaments, and heart muscle by the body - Uses a. Involved in wound healing b. Plays important role in molecular recognition c. Component in certain medical wound dressings that use collagen to stimulate wound healing d. Work with vitamin C to promote healthy connective tissue e. Helps in healing cartilage and strengthening joints, tendons and heart muscle 9. Serine (Ser) - An alcohol because it contains a methyl side chain which has a hydroxyl group - Uses a. Fundamental for proper metabolism of fats and fatty acids b. Important role in the body’s synthetic pathways for pyrimidines, purines, creatine and porphyrins c. Component of myelin sheath surrounding nerve fibers d. Aids in the production of Immunoglobulind and antibodies for preservation of a healthy immune system e. Included as a natural moisturizing agent in many skin care preparations 10. Tyrosine(Tyr) - Metabolically synthesized from phenylalanine to become the para-hydroxy derivative of phenylalanine - Uses a. Precursor of adrenal hormones epinephrine, norepinephrine, and dopamine and the thyroid hormones, including thyroxine b. Aids in the functions of adrenal, thyroid, and pituitary glands c. Stimulates metabolism and nervous system d. Mood elevator, suppresses appetite, helps reduce body fat e. Useful in the treatment of chronic fatigue, narcolepsy, anxiety, depression, low sex drive, allergies and headaches V. Additional Amino Acids A. New Amino Acids 1. Selenocysteine (Sec) - Not coded directly in the genetic code - Encoded by a UGA codon, which is a stop codon - Present in several enzymes, such as formate dehydrogenases, glycine reductases, and some hydrogenases 2. Pyrrolysine (Pyr) - Twenty second naturally occurring genetically encoded amino acid - Used by some archaea in enzymes that are part of their methane-producing metabolism - Lysine derivative - Encoded by UAA, UGA, UAG codon, normally a stop codon Prepared by: Giana Grace Manuel, RPh 6  B. Less Common Amino Acids 1. Hydroxyproline and Hydroxylysine - Found in collagen - Contains an extra hydroxyl group which provides extra hydrogen-bonding opportunities 2. Selenocysteine - Resembles cysteine in structure, albeit with selenium atom replacing sulfur atom in the side chain - Appears in a few proteins such as glutathione peroxidase 3. Ornithine - Similar to lysine with an amino group at the end of its side chain - Important player in the urea cycle - Precursor to arginine and certain polyamides 4. Citrulline - Derived from carboxylation of ornithine on the side chain - Important in the urea cycle 5. Homocysteine - Intermediate in the catabolism of methionine - Closely connected to the functioning of methyl-donor compound 6. Gamma-aminobutyric Acid (GABA) - Important neurochemical that inhibits neuronal action by binding to a specific receptors both pre- and post- synaptic VI. Classification of Amino Acids A. According to Structure Aliphatic Amino Acids - Prosthetic group is either a branched chain or a straight chain and does not have a cyclic structure 1. Neutral Amino acids a. Hydrocarbon containing - Glycine - Alanine - Valine - Leucine - Isoleucine b. Sulfur containing - Cysteine - Methionine Prepared by: Giana Grace Manuel, RPh 7  c. Hydroxyl containing - Serine - Threonine 2. Acidic Amino Acids a. Aspartic acid b. Glutamic acid 3. Basic Amino Acids a. Asparagine b. Glutamine c. Lysine d. Arginine Aromatic Amino Acids - Those having benzene 1. Phenylalanine 2. Tyrosine 3. Tryptophan 4. Tyrosine Heterocyclic Amino Acids 1. Proline 2. Histidine B. According to Polarity Non Polar Polar 1. Alanine 1. Arginine 2. Isoleucine 2. Asparagine 3. Leucine 3. Aspartic acid 4. Methionine 4. Cysteine 5. Proline 5. Glutamic acid 6. Phenylalanine 6. Glutamine 7. Tryptophan 7. Glycine 8. Tyrosine 8. Histidine 9. Valine 9. Lysine 10. Serine 11. Threonine Prepared by: Giana Grace Manuel, RPh 8 C. Nutritional Classification Non Essential Amino Acids - Amino acids that can be sythesized in the body Semi-essential Amino Acids - Can be synthesized by adults but not by growing children - Arginine and Histidine Essential Amino Acids - Cannot be sythesized by the body - Amino acids that needs to be supplied from diet - Failure to obtain essential amino acids can result in degradation of body’s proteins, muscle etc. - Tyrosine is produced from phenylalanine, so if diet is deficient in phenylalanine, tyrosine will be required as well D. According to Metabolic Fate - The carbon skeleton of amino acids can serve as a precursor for the synthesis of glucose or fat or both Glucogenic Amino Acids - Generate precursors of glucose or glycogen, such as pyruvate or a citric acid cycle intermediate Ketogenic Amino Acids - Generate ketone bodies - Synthesize fat from amino acids Examples: degraded to acetyl-coA or acetoacetyl-coA 1. Leucine 2. Lysine Glycogenic and Ketogenic Amino Acids - Precursors for glucose and fat synthesis Examples: 1. Isoleucine 2. Phenylalanine 3. Tryptophan 4. Tyrosine 5. Threonine Prepared by: Giana Grace Manuel, RPh 9 VII. Amino Acids as Drugs 1. D-Penicillamine (D-dimethylglycine) - Metabolite of penicillin employed in chelation therapy of Wilson’s disease - Can effectively chelate copper 2. N-acetylcysteine - Used in cystic fibrosis and chronic renal insufficiency - Can function as an antioxidant - Used as antidote for acetaminophen overdose. 3. Gabapentin - Used as an anticonvulsant Prepared by: Giana Grace Manuel, RPh 10