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MODULE 2  PHARMACOGNOSY  BIOCHEMISTRY PHARMACOGNOSY I. INTRODUCTION Indigenous  plant grows in their native countries PHARMACOGNOSY is applied science that deals w/ the biological, Naturalized  grew in foreign l...

MODULE 2  PHARMACOGNOSY  BIOCHEMISTRY PHARMACOGNOSY I. INTRODUCTION Indigenous  plant grows in their native countries PHARMACOGNOSY is applied science that deals w/ the biological, Naturalized  grew in foreign land other than their native countries biochemical & economic features of drugs of Natural Substances  found in nature that comprise whole plants & herbs biologic origin & their constituents. Derivatives/ Extractives  refers to single substance/s which are considered  the discipline of medicinal chemistry as chief constituents of the drugs  study of drugs of biologic origin CRUDE DRUGS  vegetable or animal drugs that consist of natural substances Focuses: 1. Identification of plants and animals that have undergone only the presence of COLLECTION & DRYING. 2. Chemistry DRUG CONSTITUENTS 3. Evaluation, preservation & use or application of crude drugs Natural  directly obtained from nature 4. Toxicology  Ex: Camphor from Camphor Plants 5. History, distribution, collection and Semi-synthetic from chemical modification of a natural constituent selection Ex: Camphor  pinene  pine trees 6. Preparation and commerce Totally Synthetic manufactures from chemical synthesis Three disciplines (Basic) devoted to drugs Ex: Camphor from Cyclopentacliene 1. Pharmacology  which dealt w/ drug actions & effects 2. Pharmacognosy  covering all information on medicines PREPARATION OF CRUDE DRUGS from natural sources plants, animals, Collection  select the species to cultivate & microorganism Harvesting  gathering the samples at a specific & proper period or 3. Medicinal Chemistry  the science of synthetic drugs season Constituents:  manual labor or mechanical devices 1. Active Constituents  compounds that are responsible for Drying  removal of moisture the therapeutic effect.  -bacterial & fungal growth 2. Inert Constituent  are differentiated to active  -hydrolysis constituents  facilitates milling & grinding  have no pharmacologic activity  Examples: Cellulose, Starch, Lignin,  remove bulk  convert the drug to a form that is Albumin, Suberin, more convenient for handling. Coloring matter  fixes the constituent Secondary Constituents  ensure good keeping qualities  are influenced by three principal factors Curing  special drying process 1. Heredity (genetic composition)  drying + curing agent 2. Ontogeny (Stage of Development)  enhance the properties of the active ingredient 3. Environmental Factors  can produce variations  ex: Cascara sagrada in secondary plant reduced glycosides MgO x 1 yr oxidized glycoside constituents include soil, (irritating) (less irritating) climate, associated flora, & methods of cultivation Garbling final step in the preparation of crude drugs Drug Biosynthesis/ Biogenesis  study of the biochemical physical process of removing extraneous material pathways leading to the Packaging, storage, preservation formation of secondary for protection & marketability constituents used as drugs. Preservation of Crude Drugs: Exposure of the drug to 65C Temperature  simplest form in preventing BRIEF HISTORY insect attacks & other form of destruction Papyrus Ebers  Egyptian document Methyl Bromide  is used in the fumigation of large lots of crude drugs  Details the use of plant & animals in medicine Chloroform (Carbon Tetrachloride)  used to control Insect Attack by  By George Ebers adding few drops to the container Dioscorides  Greek Physician Methods of Evaluation of Crude Drugs  De Materia Medica Organoleptic or morphological (leaves, barks, roots, stem) description of ~600 medicinal plants   color, odor, taste, size, shape, & special features, Claudius Galen Greek pharmacist-physician  “Galenical Pharmacy” like touch, texture method of processes of preparing Microscopic  detects cellular tissues, trichomes, stomata, starch formulas containing animal & plant drugs granules, calcium oxalate crystals aleurone grains C.A. Sydler  Coined the term Pharmacognosy Chemical  isolation, purification, identification  pharmakon “drug” Physical  moisture contents, specific gravity, optical rotation,  gnosis “knowledge”  refractive, melting point, viscosity, & solubility J.A. Schmidth First one to use the term Pharmacognosy in literature Biological  antifertility activity, anti ulcers activity, etc. Joseph  French Pharmacist Caventou  Quinine w/ the collaboration of Pelletiere CLASSIFICATION OF DRUGS Pierre  Phytochemist Morphologic  Based on the part used Robiquet  Codein Classification  Ex: Root crop, seed gums, etc  Narcotine Taxonomic  Based on the natural relationship or Rudolf Brandes  German Pharmacist  Hyoscyamine Classification phylogeny Philip Geiger  Atropine w/ the collaboration of Rudolf Brandes  Ex: Plant Families: Rutaceae Theophrastus  Father of Botany Pharmacologic  Based on therapeutic activity Classification  Ex: Hallucinogens, Anticholinergic Chemical  Based on the chemical class of the Classification constituents II. CARBOHYDRATES & RELATED COMPOUNDS A. Monosaccharides  simplest CHO units Carbohydrates  most abundant group of organic molecules in  cannot by hydrolyzed into simpler sugar nature  undergoes mutarotation  is the first product formed during Photosynthesis 1. Diose (2C)  Hydroxyacetaldehyde 2. Triose (3C) First product of synthesis is Glucose  Aldotriose: Glyceraldehydes  Ketotriose: Dihydroxyacetone Polyhydric aldehydes & Ketones 3. Tetrose (4C) – Erythrose Aldehyde: RCOH 4. Pentose (5C) Ketones: RCOR ▪Ribose  aldopentose product of gum hydrolysis Contain C, H, O in the Empiric Formula found in RNA (Ribonucleic Acid) ▪Ribulose Ketopentose Functions: -Source of Energy (Glucose ▪Xylose  Aldopentose -Storage of Energy  “wood sugar” Plants: STARCH from woody part of plant Animals: GLYCOGEN  not found free –Xylan Polymer -Cell components: Glycoproteins -Structural Component: Cellulose, Chitin diagnostic aid for intestinal absorption absorbed by not metabolized Classes: Sugar: Monosaccharides ▪Xylulose – Ketopentose Disaccharides Polysaccharides Test for Pentoses: -Bials Test Anthrone Test  general test for Carbohydrate -Benzidine Test which yields a blue or green solution 5. Hexose (6C)  most important monosaccharides ▪Glucose – aka Dextrose Energy: 1 gram of Carbohydrate = 4 kcal of Energy  Aldohexose  aka “grape sugar” “physiologic sugar” “blood sugar” “corn sugar”  -D-glucose  most abundant in nature  primary product of photosynthesis  controlled enzymatic hydrolysis of starch  nutrient  Normal value in the blood: 80-120mg% Preparation (Forms) –Glucose Dextrose excipient  crystalline dextrose monohydrate  less rigrous purification  pharmaceutic necessity Liquid glucose  product of incomplete (acid) hydrolysis of starch Dextrates  mixture of saccharides 93% dextrose  pharmaceutic necessity ▪Fructose  aka Levulose  Ketohexose –Seliwanoff Test  “Fruit Sugar” (from Honey); “Sweetest Sugar”  sweetest sugar but bitter after taste  from the inversion of aqueous solutions of Sucrose  Glucose + Fructose  from hydrolysis of inulin (fructose polymer)  nutrient  high fructose sweetener =from glucose glucose isomerase fructose Streptomyces spp. ▪Galactose  aldohexose  “Brain Sugar”  most rapidly absorbed from the small intestines  C4 epimers w/ glucose  found in milk (lactose = glucose + galactose) Nerve Fibers compose of Galactose 6. Heptose (7C) – Sedoheptulose 7. Nonose (8C) – Sialic Acid (or neuraminic acid) B. Disaccharides  two monosaccharide units linked by glycosidic bond C. Oligosaccharides  3-10 monosaccharide units 1. Sucrose  “Table Sugar”; “Invert Sugar” 1. Maltose  3 glucose units (-1,4)  glucose + fructose ( 1,2) intermediate product of acid hydrolysis  non-reducing sugar (no free carbonyl)  is the only disaccharide that occurs in free state 2. Dextrin several glucose units almost disaccharides are bound  responsible for the browning of bread  Sources: -Sugar Beets (Beta vulgaris)  product of partial hydrolysis o starch cut into limpsilver = Cosettes -Sugar Cane (Saccharum officinarum) -Sugar Mapple (Acer saccharum)  Preparation: 1. Sugar Cane Juice is boiled w/ Lime Lime  basic compound neutralize plant acids  coagulate albumins  Uses: ▪Pharmaceutic Necessity Syrup, NF mask disagreeable taste of drugs 85% sucrose sufficient bacteriostatic sel-preserving ▪Demulcent ▪Nutrient Saccharose  is almost universally distributes sugar in green leaves & in stems Invert Sugar  is darker & sweeter than sucrose 2. Maltose Malt Sugar  Glucose + Glucose ( -1,4)  reducing sugar  major degradation product of starch hydrolysis 3. Lactose  Milk Sugar  Glucose + Galactose ( -1,4)  reducing sugar found in cow’s milk (Bos Taurus) Uses: ▪Tablet diluent ▪Infant feeding (nutrient) establishes normal gul flora (Lactobacillus spp.) 4. Milk Products Whole Milk -churned Butter Buttermilk Separation Cream Skimmed Milk Rennin Whey Coagulum treated Cheese ▪Condensed Milk  partial evaporation in vacuum & consequent sterilization sterilized, sealed in hermetic container by autoclaving ▪Malted Milk  evaporated w/ Malted Extract ▪Kumyss fermented Milk ▪Whey  the liquid separated from coagulum  liquid left after skimmed milk is treated w/ rennin ▪Rancid Flavor of Butter left at room temperature is due to Butyric Acid 5. Lactulose (Duphalac®, Lilac®)  semisynthetic sugar, from the alkaline rearrangement of lactose  Fructose + Galactose (-1,4)  laxative, to reduce straining in defecation  MOA: SI: Not absorbed. LI: Lactulose is fermented by bacteria to lactic acid & acetic acid laxative action D. Polysaccharides  “glycans”  complex, high MW polymer of monosaccharides 1) Homoglycans  only 1 type of monosaccharide 1. Cellulose  structural polysaccharides in plant; -1,4  dietary fiber  makes up the cell wall of plants  Forms: Purified Cotton (Gossypium hirsutum) Powdered Cellulose Microcrystalline Cellulose Forms of starch: Purified Rayon ▪Starch paste – dispersing starch in Cellulose Derivatives: cold water -Methylcellulsoe -Ethylcellulose boiled granules swell & rupture -Hydroxypropylmethyl cellulose resulting to -Pyroxylin: Soluble guncotton/ translucent Cellulose Trinitrate mixtures solution to make collodions ▪Pregelatinized Starch –all the granules have been ruptured in the presence of  obtained by the action of water nitric & sulfuric acid in serve as plasma expander in cotton  Collodion = Pyroxylin + Ether/ Alcohol 6% concentration  Flexible Collodion = Collodion + ▪Hetastarin –water-soluble form; 3% Castor oil+  >90% amylopectin; Camphor  plasma expander -Cellulose acetate phthalate -Caboxymethylcellulose 2. Chitin  structural polysaccharides in animals & fungi  homopolyglycan of N-acetylglucosamine Galacturonic Acid  present in Chitin that cannot be ▪Sodium Starch Glycolate – a semisynthetic sodium found in cellulose salt of carboxymethyl 3. Starch  Storage of Polysaccharide In plants ether of starch  reserve carbohydrate of plants – disintegrating agent in components: tablet formation Amylose Amylopectin ▪Glutens – tacky proteins removed from corn & wheat -amylose -amylose in the preparation of starch Linearity Linear Branched 4. Glycogen – storage polysaccharides in animals - 1,4 (every 25-30 units) more branched than starch - 1,4 & -1,6 (branches every 10 units) Solubility Less soluble More soluble in  stored in the liver & skeletal muscles in H2O in water water  similar structure w/ Amylopectin Size 250-300 >1000 units 5. Inulin  Polyfructan units  abundant in the substance Iodine Dark-blue Blue-violet members of family Asteraceae Iodine Test  confirmatory test for starch  Improve digestion  consists of a greater proportion of amylopectin than  used in culture media as a fermentative identifying amylase agent for certain bacteria & in spinal laboratory Amylose  hydrolysis product of starch methods for the evaluation of renal function responsible for forming a Diagnostic aid to estimate GFR dark complex w/ Iodine (Glomerular filtration rate) *-amylaseenzyme in pancreatic juice & saliva -filtration *-amylaseremoves maltose units from the -reabsorption non-reducing ends of -secretion polysaccharide molecules 6. Dextran – homopolyglycan -1,6  usually isolated from: Rhizome  from sucrose by the action of transglycolase Fruit enzyme system in Leuconostoc mesenteroides Seed  plasma expander Official Sources of Starch:  iron dextran – hematin IV/IM ▪Corn ( Zea mays) 2) Heteroglycan  more than one type of polysaccharides ▪Potato (Solanum tuberosum) Ex: D-gluco – D-mannan ▪Rice (Oryza sativa) ▪Wheat ( Triticum aestivum) Unofficial Sources of Starch: ▪Arrow root ( Maranta Arundinacea) Uses of Starch: Dusting powder Tablet-diluent,binding,(starch paste) Tablet disintegrant Antidote for iodine toxicity E. Metabolically-related Drugs 1. Acids Cherry juice – Prunus cerasus  Malic Juice  to make cherry syrup Citric acid – tricarboxylic acid COOH HO COOH COOH  lemon juice; -first isolated by Scheele  buffer, acidulants in effervescent formulations  salt = Systemic Alkalinizer – Potassium Citrate (Acalka®) Anticoagulant – Citrated Tubes Lactic Acid  Alpha Hydroxy Propionic Acid – lactic fermentation of sugars  acidulant in infant feeding formulation  substance accumulates in the muscle as a result of vigorous exercise Tartaric Acid – dicarboxylic acid  by product of the wine industry buffer,acidulant in effervescent formulation  Denige’s Test – used to differentiate citric & tartaric acids (citrates & tartrates) Sugar Acids  produce from the oxidation of Disaccahrides & Monosaccharides (except sucrose) Aldonic Acid  produce from the oxidation of sugar’s aldehyde group (group 1) Oxalic Acid  an organic acid found in fruits of Averboa balimbi is used as Bleaching Agent Acetic Acid  laxative action; used as Food Preservative Concentrated Acid  change monosaccharide to Furfural 2. Alcohols Ethanol  >92.3% by weight, 94.9% volume of ethyl alcohol at 15.56C  from fermentation & distillation  70% = localanti-infectives Diluted alcohol – 48.4 to 49.5 % ethanol at 15.56C Distilled Spirits: (produced by Distillation) Brandy – distilled fromWine Whiskey – distilled from Malted Grain Rum – distilled from Molasses *Molasses  is the residual dark colored syrup left upon crystallization of sucrose. *Wine is sometime used medicinally as a mild stimulant & tonic *Whiskey & Brandy  CNS Depressant *In making Wine, Tannin  acts as Clarifying Agent Yeast  acts as enzyme for fermentation. Mannitol – manna –dried saccharine exudates of Fraximus ornus  laxative property: PO  osmotic diuretic: Parenteral decrease intracranial pressure usual diagnostic dose of Mannitol Injection: 200mg/kg body weight in a 15-25%solution IV in 3-5 minutes Sorbitol  D- glucitol  mountain ash (Gorbus acuparia)  half as sweet as sucrose  humectants,non caloric sweeteners  osmotic laxative at high doses  accumulates in lenses of diabetics & produces cataracts F. GUMS & MUCILAGES Carrageenan  highly-sulfated polygalactans Gums  natural plant hydrocolloids  Chondrus (C. crispus) -non-ionic  Irish Moss (Gigartina mamillosa) -anionic: Ca or Mg Salts  Stabilizer, gelling agent  transluscent & amorphous – closely related hydrocolloids that are obtained  swells when dispersed in water to form gels from various red algae ore sea weed product of plat injury as a protective  toothpaste  readily dissolve in H2O KAPPA () IOTA() LAMBDA()  precipitated by alcohol & lead acetate Stable Helix Stable Helix No stable Gums Mucilages Gelling agent Gelling agent helix readily soluble form slimy Non-gelling agent in H2O masses in H2O Thickener pathologic physiologic Danish Agar, Furcellaran  Furcellaria fastigiata products products  similar to -carragenan gelling agent 1) Shrub & Tree exudates Tragacanth – Gum Tragacanth 3) Seed Gums  Astragalus gummifer Plantago or Psyllium Seed (Metamucil®, C-lium®) Bassorin -2/3 H2O -sweet Spanish/ French Platago psyllium, Psyllium indica Tragacanthin -1/3 H2O -dissolve Indian/ Blorde – Plantago ovate Bassorin – swelling property of Tragacanth  ripe seed coat  bulk laxative  60-70% present In Tragacanth swells in water  swells in the presence of water Cydonium  Quince Seed but does not dissolve  Cydonia vulgaris Tragacanthin – composes the 30% of the  thixotropic hydrocolloid gum which is more water Guar gum  endosperm of guaran (Cyamopsis tetragonolobus) soluble component  galactomannan  most acid-resistant hydrocolloid  bulk laxative  suspending agent (5-6%) emulsifying agent  thickener, disintegrant Vermifrom Tragacanth Ribbon & flake Sorts Locust Bean Gum  endosperm of carob or St. John’ Bread Source Natural Natural Man-made (Ceratonia siliqua) injuries injuries transverse  galactomannan incision of  thickener, stabilizer; chocolate substitute main stem of branches 4) Microbial Gum Appearance Worm-like, Irregular Ribbon-like,  Xanthan Gum  high molecular weight gum twisted into tear flaked from the action of coils shaped Xanthomonas campestris Color Yellowish Yellowish Clear on a suitable CHO. brown brown (preferred grades  pseudoplastic flow Acacia  Egyptian gum, Gum Arabic  toothpaste & ointment hold/ retain shape, spread easily  Acacia Senegal Dextran Gum  Arabin = Ca, Mg, K salts of Arabic Acid 5) Plant Exudates – Pectin  swell in water Pectin  intercellular cementing material  Stable below 60% alcohol  general term for a group of polysaccharides present on  low-viscosity, but stable in wide pH range 2-10 the primary cell wall & intercellular cement  suspending agent (35-38%)  fruit rinds Demulcent, emollient, adhesive & binder  from dilute acid hydrolysis (H2SO4) of fruit rinds Ghatti Gum  Indian Gum is precipitated from the solution by an excess of alcohol is more stable in cold acid solution  Anogienssus latifolia  Sources:  more viscous than acacia; substitute for acacia Pomelo  Citrus grandis Karaya Gum  Sterculia Gum Orange  C. aurantum  Sterculia urens, S. villosa, S. tragantha Dalanghita  C. nobilis  bulk laxative, emulsifying, suspending Ponkan  C. sinensis  one of the least soluble plant gums Calamansi  C. microcarpa  swells in water  discontinuous mucilage Grapefruit  C. paradise Lemon  C. limon Apple pomace  Pyrus malus 2) Marine Gums  Forms: Algin  Sodium alginate Protopectin Unripe fruit Acid heat  Macrocystis pyrifera Pectin Soluble from, Propectose  suspending agent ripe fruit Agar Japanese Isinglass Pectinic Acid Overripe fruit  Gellidium cartilagenium Uses: Protectant Suspending Agent  Gracilaria confervoides Kaolin-pectin mixture = antidiarrheal Rhabdophycacea coat the toxin Agarose sulfate Protopectase  attacks protopectin yielding soluble Agropectin sulfate pectin Exudate  natural product of plant injury  laxative, suspending & gelling agent, solid bacteriostatic 6) Starch & cellulose Derivatives III. GLYCOSIDES Glycosides  plant constituents which produce sugars upon hydrolysis  Components: Glycone Aglycone B. Cardiac Glycosides (Genin)  have low margin of safety. Sugar component Non-sugar component *Toxicity is more likely in the presence of Hypokalemia. Common denominator Basis for classification   Test for Cardiac Glycosides: Inactive Therapeutically active - Baljet’s Test  (Beta) – only form of Glycoside that occurs in plants - Legal’s Test  yield sugars as product of hydrolysis - Keller-Keliani’s Test  are condensation product of sugar w/ various organic aglycone: steroidal hydroxyl compounds  test: Lieberman- Bustard Test  has beta--D-glucose as its most frequently occurring sugar Salkowski Test  C, S, N; O – glycosides Cardenolides Bufadienolides ”sugar ether” (R-O-R) More common Less common  Ether Bond From toad skin (Bufo spp.) Anthocyanins  pigments of flowers which is of Glycosidic Optimum activity Less activity character C23 C24 Glycone: 2 deoxysugar Test: Keller-kellani test A. Anthraquinone Exert action on the cardiac  Aglycone: Anthraquinone  Borntragers test muscles:  derivatives are colored orange-red + inotropic -cardiac  Penicillium islandium –used to study these glycosides contractility  commonly used as cathartics chromotropic - cardiac 1. Cascara Sagrada  sacred bark (Rhamnus Purshianus) rate  Cascaroides A,B – optical isomers of Barbaloin MOA: Na-K ATPase pump C,D – optical isomers of Chrysaloin USE: for Heart Failure – has reduced  Lane’s pills: Casanthrol 1. Digitalis fox glove (D. purpurea) cured with MgO x 1yr  Grecian Foxglove (D. lanata) Magnesium oxide – used to treat Cascara Constituents: Sagrada Extract to reduce ▪Digoxin  water soluble its bitter taste.  easy to control in TDM 2. Frangula  Blackthorn bark (Rhamnus frangula) (Therapeutic Drug Monitoring)  Movicol = Frangula + Karaya Gum  0.5 to 2 mg/mL 3. Aloe – dried latex or juice of the leave of: ▪Digitoxin  lipophilic Curacao Aloe: A. barbadensis, A. vera  computely absorbed Cape Aloe: A. spicata, A. ferox  most powerful glycoside for digitalis  constituents:  most lipid-soluble of the cardiac glycoside  chief principle: used in therapeutics -barbaloin (Aloin A)  long half-life (increase for toxicity) -Isobarbaloin (Aloin B)  1 digitoxigenin – aglycone  aloin  C-glycoside 3 digitoxone – glycone aloe-emodin  O-glycoside ▪Des-acetyllanatoside (Deslanoside) Uses: Cathartics initial rapid loading of digitalis Pharmaceutical aid in compound Benzoin Tincture digitalization Management of burn wounds (Aloe vera gel) Deslanoside is more soluble than Lanatoside 4. Rhubarb – dried rhizome/ root 2. Convallaria  Lily of the Valley (C. majalis) Chinese/medicinal – Rheum officinale, R. palmatum convallatoxin Ornamental – R. rhaponatum 3. Apocymum  Black Indian hemp (A. cannabinum) Indian/ Himalayan – R. emodi, R. webbianum cymarin  Principal Constituent: Rhein Anthrone 4. Adonis – Pheasant’s Eye (A. vernaliz) 5. Senna (Senokot®) – cultivated on lands resembling rice paddies  adonitoxin  dried leaflets of 5. Cactus Grandi florus – Night blooming cereus tinnevelley senna – whole leaves of (Selenereus grandiflorus) Cassia Angustifolia 6. Black Hellebore – Helle borus niger = Christmas nose alexandria senna – broken leaves of  hellebrin Cassia acutifolia 7. Strophantus – S. kombe, S. hispidus, S. gratus, Acokanthera shimperi contains Senosides A & B K- Strophantin – less toxic Sennoside is amore potent laxative than G-Strophantin  toxic form (Ouabain) Cascara Sagrada 8. Squill bulb – Mediterranean/ White Squill: Urginea maritima 6. Chrysarobin  mixture of neutral principles  Indian: Urginea indica from Goa powder (Andira avaroba) Sullarenin - bufadenolide Hot Benzene– is used to extract 50-70% yield Chrysarobin from Goa powder Not a Cathartic, keratolytic, when dissolve in benzene C. Cyanophore/ Cyanogenic Glycosides cyanogenic = produce CN upon hydrolysis E.Isothiocyanate Glycoside  rosaceous plants (Rosacease)  mustard glycosides  Test: Guignard Test  glucosinolate  Amygdalin – most common cyanophore glycosides  Cruciferus plants (Brassicaceae)  Emulsin – composite enzyme (found in almonds; causes  extracted via Expression  cause hydrolysis of -glucoside 1. Black Mustard – Sinapis Nigra  Brassica Nigra Amygdalin Sinigrin Myrosin Allyl Isothiocyanate Amygdalase  (mustard volatile oil) Prunasin 2. White Mustard – Sinapis alba Prunase   Brassica alba Mandelonitrile  less volatile Amygdalin  hydrolyzed into Glucose, Benzaldehyde, & Sinalbin Myrosin Acrinyl Isothiocyanate Hydrogen Cyanide pungent –tasting oil Vitamin B17 (aka Amygdalin)  flavoring agent  useful for SCA (sickle cell anemia) F. Flavonol Glycosides  Laetrile (Vitamin B17)  aglycone: Flavonoids Amygdalin  yellow pigment: rutin, quercitin Anticancer claims  citrus bioflavanoids: hesperidin, hesperitin, haringen Sources: Cherry – Prunus serotina  common colds Apricots – Prunus armeniaca  are abundant in the ff plant families: Almonds – Prunus amygdalus - Polygoneaceae Barley – Hordeum Vulgare - Rutaceae - Umbelliferae  Vitamin P – permeability factor D. Saponin Glycosides  rutin + hespiridin  bitter acid taste; from colloidal solutions in water  treat capillary fragility froth upon shaking: ID test – Froth Test  Elin (Ulmus sp.) – quercitin Other tests: Hemolysis Test  Milk thistle (Sylibum marianum) hepatoprotectant Capillary Tube Test Silibium (treatment of liver ailments) stermulatory = irritate mucosal membranes Sylimarin  lyse RBS (especially in Cold-blooded animals)  Ginkgo biloba (G. biloba) Test: Blood agar plate hemolysis test Ginkgolides, bilobalides aglycone steroidal sapogenins: memory enhancer neutral or acidic has a drug-herb interaction w/ ASA Liebermann-Burchard’s test Precursor for Steroids Synthesis  two types based on their Sapogenins or aglycones: G. Alcohol -Neutral Saponin – are derivatives of steroids 1. Salicin– Saligenin + D-glucose -Acid Saponin – possess triterpenoid structures (salicin alcohol) 1. Glycirrhiza  Spanish licorice: Glycirrhiza glabra produced by the hydrolysis of Salicin by Emulsin Russian licorice: G. glabra variety – Glandu lifera Salicin Emulsin Saligenin + -D-glucose  glycyrrhizin, glycirrhizic acid  Willow bark (Salix purpurea)  sweeteners; flavorant (Salix fragilis)  disguise the bitter taste of Quinine by paralyzing the  Antirheumatic, anti-inflammatory taste buds. 2. Populin  Poplar Bark (Populus spp.)  demulcent; expectorant  anti-inflammatory properties: PUD -Peptic ulcer disease H. Aldehyde Addison’s Disease 1. Vanilla  Vanilla planifolia: Mexican vera cruz -decrease hormone Bourbon vanilla production Vanilla tahitensis: Tahitian vanilla  Contraindicated w/ CHF (congestive heart failure)  Vanillin as Glucovanillin or & HTN (hypertension) Glucovanillic acid it cause Na & H2O retention  Flavoring Agent 2. Dioscorea – Mexicom vam (Dioscorea floribunda)  Synthetic analogue ethylvanillin  Diosgenin: Anti-inflammatory, precursor for steroids synthesis  botogenin, hecogenin 3. Agave (A. cantalla) – fiber, hecagenin, manogenin, gifogenin molluscide 4. Similax – Sarsa pogenin; smilagenin 5. Strophantus – sarmantogenin 6. Ginseng – source: American – Panax quinquefolus Asian – Panax ginseng  Panoxosides, Gensenosides, Chikuse/ susaponins  adaptogen I. Lactone Glycosides 1. Coumarin  lactone of -hydroxycinnamic acid  fragrant odor, bitter aromatic, burning taste  Tonka Beans (Dipterex adorata)  flavoring agent 2.Bishydoxy coumarin/ Dicumarol  improperly cured leaves of sweet clover Melilotus officinalis  first oral anticoagulant, precursor of warfarin 3. Cantharide  Spanish/ Russian/ Blistering Flies (Cantharis vesicatoria)  Cantharidin – Vesicating principle  Irritant, vesicant  remove warts urgenital tract priapism  aphrodisiac 4. Psoralens  Photosensitizing furocoumarin  Family: Rutaceae & Apiaceae  Bishop’s Flowers – Ammi majus  Methoxsalen : Xanthotoxin  Uses: Repigmentation in vertigo For symptomatic psoriasis 5. Santorin  Artemisia cing, Amaritima  Antihelminthic, Toxic 6. Isoflavones  Soybean (Glycine soja)  phytoestrogens – bind to estrogen receptors alleviate menopausal symptoms 7. Skimmin 8. Aesculin J. Phenol Glycosides 1. Uva ursi  Bearberry ( Archtostaphylo uva ursi) Arbutin available in the form of herbal teas  diuretic, astringent 2. Poison- Ivy & Oak  Rhus spp. Urushiol  a non-volatile principle producing allergic symptoms – cause delayed contact dermatitis (Other) Phenol glycosides: Arbutin (from uva ursi) Hesperidin (from citrus fruits) Phlrodzin (from root barks of rosaceous plants) Baptisin (from Baptisia) Iridin (from Iris Species) IV. Tannins Tannins  non-crystallizable hydrocolloid mixture of polyphenols  amorphous, polyhydroxy-phenolic compounds  form colloidal solutions in water  acid puckering taste (astringent taste)  precipitated by Cu, Pb, Cr2O72  precipitated gelatin, alkaloids  astringent – precipitate proteins  carcinogenic potential  alkaloidal Antidote  groups of compounds that make s wood darker in color  produced Deep Red w/ Potassium Ferricyanide & Ammonia  animal hide tanningleather  tannins Hydolyzable Non-hydrolyzable Other names Pyrogallotannins Phlobatanins condensed Hydrolytic Pyrogallol X products (given soluble Phlobaphenes compounds w/ red polymerization lead acetate) products FeCl3 Blueblack Greenblack Leather Type Bloom Leather Tanner’s Red Br2 () (+)  Hydrolyazable Tannins  consist of gallic acid or related polyhydric compounds esterified w/ glucose  Nonhydrolyzable Tanninc  most result from the condensation of 2 or more polyhydric compounds esterified w/ glucose 1. Hamamelis  Witch Hazel leaves (Hamamelis virginiana)  hamamelitannin  astringent, hemostatic hemorrhoidal preparations insect bites & stings teething preparations 2. Nutgall  hardened excrescence from the young twigs of Quercus infetoria, when a hymenopherous insect (Cynips tinctora) bores holes to deposit ova Tannic Acid (Gallotannic Acid)  is a mixture of esters of gallic acid w/ glucose principal constituent of Nutgall used as astringent  components of Universal Antidotes: 1. MgO – neutralize acid 2. Tannic acid – precipitate alkaloids 3. Activated Charcoal – adsorp poisons 3. Japanese & Chinese Galls – Rhus chinensis ; gallic acid 4. Apple  tannin-rich plant used in medicine as Astringent.  Pyrus mallus V. LIPIDS A. Fatty Acids  are absorbed in the small intestines as Such. Lipids  compounds that are insoluble in water, 1. Saturable – no double bonds soluble in organic solvent. caproic  6:0 palmitic  16:0 Fats Fixed Oils Waxes capryllic  8:0 stearic  18:0 esters of Fatty acids esters of Fatty acids esters of Fatty acids cupric  10:0 arachidic  20:0 + + + lauric  12:0 behenic  22:0 glycerols glycerols High molecular weight myristic  14:0 lignoceric  24:0 monohydric alcohol 2. Unsaturated  at least one double bond Solid Liquid Solid, undecylenic acid  11:1 (except: (except: Myristica Semisolid, from the pyrolysis of castor oil (Ricimus communis) Cod liver oil) theobroma oils) Liquid antifungal, Zn salts Saturated Unsaturated Saturated, Palmitoleic  16:1 Fatty Acids Fatty Acids Unsaturated Oleic  18:1 Fatty Acids Linoleic  18:2 Animals Plants Plants, animals Linolenic  18:3  essential fatty acid (Vitamin F) Energy Storage Energy Storage Protection, etc Arachidonic  20:4 3. Miscellaneous USP Tests: Sodium Morrhuate  sodium salts of the fatty acids in cod-liver oil #𝑚𝑔 𝐾𝑂𝐻 𝑛𝑒𝑒𝑑 𝑡𝑜 𝑛𝑒𝑢𝑡𝑟𝑎𝑙𝑖𝑧𝑒 𝑡𝑕𝑒 𝑓𝑟𝑒𝑒 𝐹𝐴 (Gaddus morrhua) 𝑎𝑐𝑖𝑑 𝑣𝑎𝑙𝑢𝑒 𝑛𝑢𝑚𝑏𝑒𝑟 = 1𝑔𝑟𝑎𝑚 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒  Antisclerosing agent for varicose veins Azelaic Acid  saturated dicarboxylic acid, 9C Saponification value  from ozomolysis of castor oil #𝑚𝑔 𝐾𝑂𝐻 𝑛𝑒𝑒𝑑 𝑡𝑜 𝑛𝑒𝑢𝑡𝑟𝑎𝑙𝑖𝑧𝑒 𝑓𝑟𝑒𝑒 𝐹𝐴  Anti-acne  𝑠𝑎𝑝𝑜𝑛𝑖𝑓𝑦 𝑒𝑠𝑡𝑒𝑟𝑠 𝐾𝑜𝑒𝑡𝑡𝑠𝑑𝑜𝑟𝑓𝑒𝑟 # = Palmites  a fatty acid which is essential but cannot be synthesized 1𝑔𝑟𝑎𝑚 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 in Human #𝑔 𝐼 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑑 𝐼𝑜𝑑𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒 𝑛𝑢𝑚𝑏𝑒𝑟 = Fatty Acids & Glycerols  are the starting materials for the 100𝑔𝑟𝑎𝑚𝑠 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒 synthesis of fats in plants. Acrolein  produces when fat are strongly heated Types of Fixed Oil Drying >120 iodine Linseed oils  Unsaturated fatty acids have lower melting points than saturated fatty acids Fish oils  Vegetable Oil  are generally liquid @ room temperature Cod-liver oils  can be transformed into solid fats by the Semi-drying 100-120 Cottonseed oils process of Hydrogenation Sesame oils  Animal Fat  are generally solid @ room temeprature Non-drying Peptides a. Proteoses  soluble in water  will not be coagulated on heating  can be precipitated by saturating their solutions w/ Ammonium sulfate b. Peptones  soluble in water  will not be coagulated on heating  cannot be precipitated by saturating their solution w/ ammonium sulfate certain alkaloidal reagents like Phosphotungstic acid, precipitate them c. Peptides  are combination of two or more amino acids, the carboxyl group of one amino acid being joined to the amino group of another VI. LEVELS OF PROTEIN ORGANIZATION 1. Primary Structure  specifies the sequence in which the various 4. Quaternary Structure  in which the individual polypeptide chains fir amino acids are linked together. each other in the native conformation of an most important of the four structural levels that oligomeric proteins determines the overall shape, function &  2 or more subunits/ domains properties of protein’s amino acid sequence  arrangement of polypeptide chains in  stabilizes by Peptide Bonds relation to one another in multi-chained  refers to the order of amino acids in the protein polypeptide chain/s & the location of the  *The bonds linking the quaternary structure disulfide bonds are all noncovalent:  unaffected w/ denaturation -Hydrogen Bonds Sickle-cell anemia  is caused by a genetic defect in blood -Electrostatic/ Salt Bonds (ionic Bond) hemoglobin(sticky) whereby Valine is occurs between basic & substituted for Glutamic Acid at only one acidic amino acids position in a chain of 146 amino acids. -Hydrophobic Bonds Ex: Collagen  has a complex quaternary structure formed 2. Secondary Structure refers to how segments of the protein chain when many tropocollagen strands aggregate are oriented into a regular pattern together by overlapping lengthwise in quarter  refers to the spatial arrangements of amino stagger arrangement acid residues close to one another in the linear sequence of a polypeptide chain Edman  the principal method for determining the primary structure of  stabilized by H-bond polypeptides Hydrogen Bonding  occurs between Denaturation  destruction of 4, 3, 2 level of protein tyrosine residues & organization w/ loss of functions carboxyl groups on Hydrolysis  destruction of 1 the side chain. Denaturant  1. High temperature Kinds of Patterns: 2. Extreme pH: ionic interaction a. -helix  encountered in proteins of the globular class 3. Organic Solvent: Alcohol  stabilized by hydrogen bond -mercapto ethanol  composedof a single linear array of helically disposed amino acids Ex: Keratin  fibrous structural proteins found in wool, hair,  Absorbable Surgical Suture fingernails & feathers aka “Catgut Suture” b. -pleated sheet  composed of 2 or more different regions of “Surgical Catgut” stretches of at least 5-10 amino acids. “Sugical Gut”  is pleated, due to positioning of the -  sterile strand prepared from collagen derived from carbons of the peptide bond healthy mammals or from synthetics polymers Ex: Fibroin  fibrous protein found in silk c. triple helix  less common kind of Pattern  Non-absorbable Surgical Suture  a strand material that is suitable Ex: Collagen resistant to the action of living d. Random Coil mammalian tissues 3. Tertiary Structure  the way in which an entire protein molecule is coiled or folded into its specific three- dimensional shape Myoglobulin Hemoglobin due to interaction of R-group  single polypeptide  2 subunits/ domains  the overall arrangement & interrelationship of  -helix  70%  subunits: 2 polypeptides various regions or domains, & individual amino  heme  porphyrin  subunits: 2 polypeptides acid residues of a single polypeptide chain ring 4  Examples: Fibrous & Globular Proteins Fe2+  02 nonpolar amino acids hydrophillic interactions Sickle cell anemia: Gene  Hemoglobin polar amino acid  H-bonding  acidic AA & basic  ionic interaction Point mutation Cysteine (-SH)  disulfide bonds Glutamic Acid  one important Ex: Myoglobulin  relative of hemoglobin; globular protein w/ component of normal a single chain of 153 amino acid residues hemoglobin found in the skeletal muscle of sea animals  negative (-) Bonds Responsible for the Tertiary Structure: Abnormal Hemoglobin a. Hydrophobic Interaction of non polar side chains the Glutamine  caused by the mutual repulsion of solvent like becomes Valine phenylalanine, alanine, & valine  b. Dipole-dipole Interaction  between serine groups Hydrophobic interaction c. Disulfide linkage  between two cysteine residues w/c forms  the cysteine molecules hemoglobin becomes sticky  responsible for curly hair Red Blood Cell in SCA: Normal: Disc-shaped Abnormal: Crescent-shaped Hemoglobin-C disease: Glu  Lysine Porphyrin  are involved in the building of Blood VII. AMINO ACIDS: Classification of Amino Acids: 1. Common/ Standard Amino Acid  one specific codon causing in DNA genetic code. Codon  sequence of three nucleotides specifying an AA. Degeneracy of Genetic Codon: 6 codons = 1 amino acids Redundancy/ Generacity  states that a given amino acid can have more than one codon that codes for it. Ex: AUG = corresponds to Methionine standard amino acid. 2. Derived Amino Acid  (from the common) Ex: Hydroxyproline  collagen (due to rigidity) Hydoxylysine  found in Elastin system AMINO ACIDS Methemoglobinemia  results from the oxidation of heme protein in NAME ABBREVIATIONS ISOELECTRIC POINT hemoglobin resulting to increased oxygen Amino Acids with Acidic Side Chains (Negatively Charged) affinity, & therefore failure to adequately deliver Aspartic Acid Asp, D 3.0 oxygen to tissue. Glutamic Acid Glu, E 3.2 Thalassemia  results from the oxidation of heme protein in hemoglobin Amino Acids with Basic Side Chains (Positively Charged) resulting to increased oxygen affinity, & therefore failure Lysine Lys, K 9.7 to adequately deliver oxygen to tissues. Arginine Arg, R 10.8 Marasmus  aka Protein-Calorie Malnutrition Histidine His, H 7.6  a state of extreme emaciation Amino Acids with Polar but Uncharged, Non-Ionic Side Chains  result from chronic deficiency of Calories, which occur even in the presence of adequate intake of protein due to OH group (Hydroxyl group) Kwashiorkor  caused by inadequate intake of protein in the presence of Serine Ser, S 5.7 adequate in take calories Threonine Thr, T 5.6 Glucosuria  may occur in other disease states. Tyrosine Tyr, Y 5.7 Anoxic  inadequate oxygen tension in air (Baguio- high altitude) due to Amide groups Anemic  lack of oxygen carriers/ hemoglobin Aspargine Asn, N 5.4 Stagnant  happens when blood circulation is retarded Glutamine Gln, Q 5.7 Histotoxic  happens when there is cell defect, & interference of cell due to SH or Thiol group metabolism Cysteine Cys, C 5.0 Atherosclerosis  is the deposition of lipid plaques on the lining of the due to H group arteries Glysine Gly, G 6.0 Gaucher’s Disease  is the accumulation of Glucocerebrosides Amino Acids with Nonpolar, Hydrophobic Side Chains Tay sach’s Disease  is the accumulation of Gangliosides with Aliphatic R group Alanine Ala, A 6.0 Leucine Leu, L 6.0 Isoleucine Ile, I 6.0 Valine Val, V 6.0 Proline Pro, P 6.3 with Aromatic Ring Phenylalanine Phe, F 5.5 Tryptophan Trp, W 5.9 with Sulfur group Methionine Met, M 5.7  Amino Acids Requirements f Humans: Amino Acids  are the monomeric units of proteins & enzymes Nutritionally Nutritionally  transported first to the Liver as it enter the Essential Nonessential circulation Arginine Alanine General Formula: R  CH  COOH Histidine Aspargine | Isoleucine Aspartate NH2 Meucine Glutamate Characteristics:  are formed from Amphibolic Methionine Glutamine 1. Amphoteric  able to react chemically as either an acid or a base Intermediates Phenylalanie Glycine COOH  acidic Threonine Hydroxyproline NH2  basic Tryptophan Proline 2. Chirality/ Optical Activity Valine Serine Except: Glycine Cysteine 3. Zwitter ions/ Dipolar Ions Tyrosine  formed from nutrionally Isoelectric species is the form of a molecule that has an equal Hydroxylysiine essential amino acids number of positive & negative charges & thus is electrically neutral. Isoelectric pH  also called as pI Cysteine  formed from methionine, which is nutritionally essential  is the pH midway between pKa values on either side Cystine  is a dimer of cysteine of the isoelectric species. Tyrosine  formed when phenylalanine hydroxylase converts phenylalanie  pH at which amino acids exist in its Zwitter ion 𝑝𝐾1+𝑝𝐾2  possess a phenolic hydroxyl group  nonionizable R-group: 𝑝𝐼 =  serves as a precursor in the synthesis of Catecholamines 2  acidic amino acid: 𝑝𝐼 = 𝑝𝐾1+𝑝𝐾2  is first hyroxylated into 3,4-dihydroxyphenylalanine, which is the 2 rate limiting step of the pathway in the synthesis of Catecholamines 𝑝𝐾1+𝑝𝐾2  basic amino acid: 𝑝𝐼 = Hydroxylysine  formed from lysine that is catalyzed by lysyl hydroxylase 2 Examples: Glutamate  formed from reductive amination of -ketoglutarate that is ▪for Alanine (that has only two dissociating groups, there is no catalyzed by glutamate dehydrogenase ambiquity) Glutamine  formed by the amination of glutamate to glutamine that is pK1 (R-COOH) = 2.35 catalyzed by glutamine synthesis pK2 (R-NH3+) = 9.69 Alanine  formed by the transamination of oxaloacetate 𝑝𝐾1 + 𝑝𝐾2 2.35 + 9.69 Aspargine formed when aspartate is catalyzed by Asapargine synthetase 𝑝𝐼 = = = 6.02 Serine  formed by the oxidation of the -hydroxyl group of the glycolytic 2 2 ▪for polyfuctional acids, pI is also the pH midway between the pKa intermediate 3-phosphoglycerate converts it to an oxoacids, whose subsequent transamination & dephosphorylation leads to Serine values on either side of the ionic species. Tryptophan  synthesizes Serotonin (5-hydroxytryptamine)as precursor Aspartic Acid  is used in the synthesis of Niacin (Vitamin B3) 𝑝𝐾1 + 𝑝𝐾2 2.09 + 3.96 𝑝𝐼 = = = 3.02 Histidine  when carboxylated, yield Histamine 2 2 Glycine  formed when aminotransferases can catalyzethe synthesis of ▪for Lysne (basic Amino acids) glycine from glyoxylate & glutamate or alanine pK1 = 2.2  important portion of hemoglobin pK2 = 9.2  the only amino acid without an asymmetric carbon pK3 = 10.8  simplest amino acid 𝑝𝐾1 + 𝑝𝐾2 2.2 + 9.2 Proline formed from glutamate by reversal of the reactions of proline 𝑝𝐼 = = = 5.7 2 2 catabolism 4. UV absorption  responsible for sirupting the -helix Amino acids do not absrov visible light & thus are colorless, but  has an imino group Tyrosine Hydroxyproline  formed from proline that is catalyzed by prolyl hydroxylase Phenylalanine absorbs wavelength(250-290nm) Valine, Leucine, Isoleucine  are nutritionally amino acids, Tryptophan ultraviolet light Tissue aminotransferases reversibly Tryptophan  makes the major contribution to the ability of most interconvert all three amino acids, & their corresponding -keto acids. proteins to absorb light in the region of 280nm. -keto acids  can replace their amino Native Conformation  refers to normal folded protens acids in the diet Misfolding(protein)  cause Disease Selenocysteine  is not normally considered an amino acid present I proteins, but it occurs at the active sites of several enzymes. Protein Misfolding Disease: Example of Enzymes: 1. Alzheimers Disease -theoredoxin reductase Amyloid Precursor protein (APP) secretases  AB40 + AB42 -glutathione peroxidase  misfolding -deiodinase (that converts thyroxine to triiodothyronine) Aggregates/ fibrils  Glutamate  neurotransmitter biosynthesis L--amino Brain Tyrosine  formation of thyroid hormones 2. BSE (Bovine Spongiform Encephalopathy) acids Ornithine  mad cow disease (because first observe in cow) Citrulline participate in urea synthesis  cause by abnormal prion (proteinaceous protein only) Arginosuccinate  misfolding D-serine D-amino Brain tissue Fibrils infection brain (holes) D-aspartate acids Abnormal Prion heat & protease resistance onlty D-alanine Cell walls of gram-positive bacteria  can misfold the normal prion D-glutamate Credzfeldt-Jakob  spongiform in human but not the BSE With exception of Glycine, all naturally occurring amino acids Chaperons  protein help in the folding of other protein are L--amino acids 1. Heat-shock proteins 2. Chaperonin Transamination  conversion amino acids to keto acids. Aminoacyl residues  Amino acids present in peptides;  are named by replacing the –ate or –ine suffixes of free amino acids with –yl (eg. alanyl, aspartyl, tyrosyl) -Peptides are the named as derivatives of the carboxyl terminal amiacyl residue. Example: Lys-Leu-Tyr-Gln (is called lysyl-leucyl-tyrosyl-glutamine) The –ine ending on glutamine indicates that its - carboxyl group is not involved in peptide bond formation. Types of Chromatography (prior to Protein Analysis) Chemical Reactions of Amino Acids & Proteins 1. Column Chromatography Employs as the stationay phase a Ninhydrin Reaction  Oxidative deamination acolum containing small spherical  used yo detect amino acids in beads of modified cellulose, Chromatographic Analysis acrylamide, or silica whose surface specific for amino acid & free amino typically has been coated w/ an group chemical functional groups. yields Blue product w/ all amino acids 2. Partition Chromatography yields Yellow w/ Proline (imino acid) & 3. Size Exclusion Chromatography Gel filtration Hydroxyproline Biuret Test  general test for proteins, specifically on Separates proteins based on their peptide linkage stokes radius, the diameter of the  protein will give blue-violet color by sphere using copper sulfate & sodium Employs porous beads. hydroxide as reagents 4. Absorption Chromatography The protein mixture is applied to a Xanthoproteic Reaction  for tyrosine, tryptophan & column under conditions where phenylalanine the protein of interest associates  yields orange or red color with the stationary phase so Millon-Nasse Reaction  for phenolic ring of tyrosine tightly that is partition coefficient  gives positive result yielding is essentially un