Pharmacology of Cardiac Glycosides and Vitamins
43 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the mechanism of action for cardiac glycosides?

  • Increase in Na+ concentration inside the cell
  • Inhibition of Na+/K+ ATPase enzyme (correct)
  • Decrease in Ca+2 concentration
  • Promotion of K+ transport into the cell

    • What is metabolism?

    The chemical transformations occurring in the cells of living organisms essential for life.

    What are the primary glycosides found in Strophanthus kombe?

    K-strophanthoside, K-strophanthin-B, and cymarin

    What is a primary metabolite?

    <p>A metabolite directly involved in normal growth, development, and reproduction.</p> Signup and view all the answers

    Ouabagenin is safe for oral administration.

    <p>False</p> Signup and view all the answers

    What is the main constituent of Nerium oleander used to treat cardiac insufficiency?

    <p>Oleanderin</p> Signup and view all the answers

    Give an example of a primary metabolite used in industrial microbiology.

    <p>Alcohol, such as ethanol or citric acid.</p> Signup and view all the answers

    What properties does squill possess?

    <p>Expectorant, emetic, cardiotonic, and diuretic</p> Signup and view all the answers

    What are secondary metabolites?

    <p>Organic compounds produced through modification of primary metabolite synthases that do not play a main role in growth.</p> Signup and view all the answers

    Which of the following statements about squill is true?

    <p>It is primarily used as rat poison</p> Signup and view all the answers

    What is the role of atropine?

    <p>It acts as a competitive antagonist for acetylcholine receptors.</p> Signup and view all the answers

    What process captures light energy to produce glucose?

    <p>Photosynthesis.</p> Signup and view all the answers

    Where does photosynthesis mainly occur?

    <p>In chloroplasts.</p> Signup and view all the answers

    What is produced during the light-dependent reactions of photosynthesis?

    <p>ATP and NADPH.</p> Signup and view all the answers

    What is the Calvin Cycle?

    <p>A light-independent process where sugar molecules are formed from carbon dioxide.</p> Signup and view all the answers

    The citric acid cycle (Kreb’s cycle) occurs in the ______.

    <p>mitochondrial matrix</p> Signup and view all the answers

    What is the function of vitamins in the body?

    <p>They are essential for the maintenance of normal metabolic functions.</p> Signup and view all the answers

    Which of the following are fat-soluble vitamins? (Select all that apply)

    <p>Vitamin D</p> Signup and view all the answers

    What is Vitamin A primarily derived from?

    <p>Fish liver oils and some plant carotenoids.</p> Signup and view all the answers

    What are the main sources of Vitamin D3?

    <p>Egg yolk</p> Signup and view all the answers

    Which vitamin deficiency can lead to night blindness?

    <p>Vitamin A</p> Signup and view all the answers

    Vitamin E acts primarily in blood clotting.

    <p>False</p> Signup and view all the answers

    What is the primary function of Vitamin K?

    <p>Blood clotting</p> Signup and view all the answers

    What is a primary dietary source of Vitamin B1?

    <p>Cereal grains</p> Signup and view all the answers

    Vitamin B3 is also known as ______.

    <p>niacin</p> Signup and view all the answers

    What deficiency is associated with beriberi?

    <p>Vitamin B1</p> Signup and view all the answers

    Vitamin B6 is important for amino acid metabolism.

    <p>True</p> Signup and view all the answers

    What role does Vitamin B7 (biotin) play in metabolism?

    <p>Transfers carbon dioxide</p> Signup and view all the answers

    Which vitamin is known as the sunshine vitamin?

    <p>Vitamin D</p> Signup and view all the answers

    Match the vitamins to their key functions:

    <p>Vitamin A = Night vision Vitamin D = Calcium absorption Vitamin E = Antioxidant Vitamin K = Blood clotting</p> Signup and view all the answers

    What is the role of Biotin in cellular reactions?

    <p>It is involved in fat and protein metabolism of hair roots, fingernails, and skin.</p> Signup and view all the answers

    Which of the following are sources of Vitamin B9?

    <p>Beans</p> Signup and view all the answers

    Vitamin B12 is also known as __________.

    <p>cobalamin</p> Signup and view all the answers

    Vitamin C is the most stable of all vitamins.

    <p>False</p> Signup and view all the answers

    What condition can Vitamin C deficiency lead to?

    <p>Scurvy</p> Signup and view all the answers

    What do glycosides consist of?

    <p>A sugar portion linked to a non-sugar moiety.</p> Signup and view all the answers

    Which type of glycosides yields sugars upon hydrolysis?

    <p>C-glycosides</p> Signup and view all the answers

    Match the glycosides with their classification:

    <p>C-glycosides = Sugar attached through C-C bond O-glycosides = Sugar attached through O-C bond S-glycosides = Sugar attached through sulfur N-glycosides = Sugar attached through nitrogen</p> Signup and view all the answers

    Glycosides are generally soluble in non-polar organic solvents.

    <p>False</p> Signup and view all the answers

    Which of the following is NOT a property of glycosides?

    <p>Sweet taste</p> Signup and view all the answers

    What are cardioactive glycosides characterized by?

    <p>Their specific action on cardiac muscle.</p> Signup and view all the answers

    What is the main use of Digitalis?

    <p>It is used to treat heart-related conditions.</p> Signup and view all the answers

    The aglycone in cardiac glycosides is referred to as __________.

    <p>cardiac genin</p> Signup and view all the answers

    Study Notes

    Metabolism and Metabolites

    • All chemical reactions in a living organism's cells
    • Essential for life
    • Metabolites are end products or intermediates of metabolic processes
    • Primary metabolites play a role in normal growth, development, and reproduction.
    • They are usually produced during growth phase and are considered essential for proper growth.
    • Examples include ethanol, lactic acid, and certain amino acids.
    • Many are produced industrially such as alcohol, L-glutamate, L-lysine, and citric acid.
    • Secondary metabolites are typically organic compounds produced through the modification of primary metabolite synthases.
    • They do not play a main role in growth, development, and reproduction.
    • Usually formed during end or near stationary phase of growth.
    • Many have a role in ecological function including defense mechanism, by serving as antibiotics and by producing pigments.
    • Examples of secondary metabolites with importance in industrial microbiology include atropine, erythromycin, and bacitracin.

    Photosynthesis

    • Is the process by which light energy is captured, converted, and stored in a simple sugar molecule.
    • This occurs in chloroplasts and other parts of green organisms.
    • It is a backbone process for all life on Earth.
    • Equation: 6CO2 + 12 H2O + light energy -> C6H12O6 + 6O2 + 6H2O
    • During the process, carbon dioxide enters through the stomata, and water is absorbed by the root hairs from the soil.
    • Chlorophyll absorbs light energy from the sun to split water molecules into hydrogen and oxygen.
    • Hydrogen and carbon dioxide are used in the production of glucose.
    • Oxygen is released as a waste product.
    • Glucose is a source of food for plants and provides energy for growth and development.
    • Pigments are molecules involved in photosynthesis that impart color by absorbing light at specific wavelengths.
    • Green plants contain chlorophyll a, chlorophyll b, and carotenoids, which are present in the thylakoids of chloroplasts.
    • Chlorophyll-a is the main pigment used to capture light energy.

    Light Reaction of Photosynthesis

    • Takes place in the thylakoid membranes of chloroplasts during the day in the presence of sunlight.
    • The Grana, membrane-bound sacs like structures present inside the thylakoid gather light and are called photosystems.
    • These photosystems have large complexes of pigment and protein molecules that play a role in the light reactions of photosynthesis.
    • There are two types of photosystems: photosystem I and photosystem II.
    • Light energy is converted to ATP and NADPH in the light-dependent reactions, which are used in the second phase of photosynthesis.
    • ATP and NADPH are generated by two electron-transport chains, water is used, and oxygen is produced.
    • Equation: 2H2O + 2NADP+ + 3ADP + 3Pi → O2 + 2NADPH + 3ATP

    Dark Reaction of Photosynthesis (Light-independent reaction)

    • Also called carbon-fixing reaction.
    • It is a light-independent process where sugar molecules are formed from water and carbon dioxide molecules.
    • The dark reaction occurs in the stroma of the chloroplast, utilizing the NADPH and ATP products of the light reaction.
    • Plants capture carbon dioxide from the atmosphere through stomata and proceed to the Calvin photosynthesis cycle.
    • In the Calvin cycle, ATP and NADPH convert 6 molecules of carbon dioxide into one sugar molecule or glucose.
    • Equation: 3CO2 + 6 NADPH + 5H2O + 9ATP → G3P + 2H+ + 6 NADP+ + 9 ADP + 8 Pi
    • G3P – glyceraldehyde-3-phosphate

    Reactions of the Calvin Cycle

    • They can be divided into 3 main stages: carbon fixation, reduction, and regeneration of the starting molecule.
    • In carbon fixation, a CO2 molecule combines with a five-carbon acceptor molecule, ribulose-1,5-bisphosphate (RuBP).
    • This results in a six-carbon compound that splits into two molecules of a three-carbon compound, 3-phosphoglyceric acid (3-PGA).
    • This reaction is catalyzed by the enzyme RuBP carboxylase/oxygenase, or rubisco.
    • In the reduction stage, ATP and NADPH convert the 3-PGA molecules into molecules of a three-carbon sugar, glyceraldehyde-3-phosphate (G3P).
    • This stage is called reduction because NADPH donates electrons to, or reduces, a three-carbon intermediate to make G3P.
    • In regeneration, some G3P molecules are used to make glucose, while others are recycled to regenerate the RuBP acceptor.
    • Regeneration requires ATP and involves a complex network of reactions.

    Glycolysis

    • The metabolic pathway that converts glucose into pyruvate.
    • Occurs in the cytosol and is oxygen-independent.
    • The free energy released during the biochemical reactions in glycolysis is used to generate a net gain of two molecules of ATP.

    Citric Acid Cycle (Krebs' cycle)

    • A series of enzyme-catalyzed reactions occurring in the mitochondrial matrix where acetyl-CoA is oxidized to form carbon dioxide, and coenzymes are reduced, which generate ATP in the electron transport chain.
    • It is an eight-step process.
    • Takes place in the matrix of mitochondria under aerobic conditions.

    Biosynthetic Pathways of Secondary Metabolites

    • A multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms.
    • In biosynthesis, simple compounds are modified, converted into other compounds, or joined together to form macromolecules.
    • This process often consists of metabolic pathways.
    • Building blocks are tiny chemical molecules produced from primary metabolites mostly from photosynthesis, glycolysis, and or Krebs cycle.
    • They are very important in biosynthesis and production of secondary metabolites.
    • They are considered to be intermediates, few important ones are acetyl CoA, shikimic acid, mevalonic acid, malonic acid.

    Building Blocks based on the Number of Carbon Units

    • C1 derived from S methyl of L-methionine
    • C2 derived from acetyl –CoA
    • C5 derived from isoprene units
    • C6-C3 units (phenyl propyl units) are derived from phenylalanine or tyrosine through the shikimic acid pathway.

    Basic Metabolic Pathways Leading To Production of Secondary Metabolites Through Photosynthesis

    • Shikimate pathway
    • Malonate/Acetate pathway
    • Mevalonate pathway

    Shikimate Pathway

    • Basic pathway for biosynthesis of phenolic compounds, alkaloid, and others.
    • Takes place in chloroplast plant cells and have the phenylpropanoid precursors.
    • These aromatic compounds are types of secondary metabolites that are abundant in plants, and the expression of them are triggered by environmental stresses, such as pathogens and herbivores attack, inappropriate pH and temperature, UV radiation, saline stress, and heavy metal stress.
    • This pathway is used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (phenylalanine, tyrosine, and tryptophan).
    • The pathway starts with two substrates, phosphoenol pyruvate and erythrose-4-phosphate, and ends with chorismate, a substrate for the three aromatic amino acids.
    • Known as the chorismate pathway.
    • Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-D-arabino-heptulosonate 7-phosphate using the enzyme DAHP synthase.
    • Shikimate kinase phosphorylates shikimate to form shikimate 3-phosphate.
    • Shikimate-3-phosphate and phosphoenol pyruvate are coupled to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase.
    • 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a chorismate synthase.
    • Chorismate produces Tryptophan (L-Trp), Tyrosine (L-Tyr), and Phenylalanine (L-Phe) as building blocks for proteins, alkaloids, phenols, and other biosynthesis.
    • Connects central and specialized metabolism in the plant cell and carbon degradation during the synthesis of secondary metabolite compounds.

    Malonic-acid (Malonate/Acetate) pathway

    • Involves acyl carrier protein (ACP) to yield fatty acylthioesters of ACP.
    • These acyl thioesters form important intermediates in fatty acid synthesis.
    • These C2 acetyl CoA units at the later stage produces even numbers of fatty acids from n-tetranoic (butyric) to n-ecosanoic (arachidic acid).
    • Acetyl‐CoA is the direct precursor only of the methyl end of the growing fatty acid chain.
    • All the other carbons come from the acetyl group of acetyl‐ CoA but only after it is modified to provide the actual substrate for fatty acid synthase.
    • Malonyl‐CoA contains a 3‐carbondicarboxylic acid, malonate, bound to Coenzyme A.
    • Malonate is formed from acetyl‐CoA by the addition of CO2 using the biotin cofactor of the enzyme acetyl‐CoA carboxylase.

    Mevalonic-acid (Mevalonate) pathway

    • Also known as the isoprenoid pathway.
    • Involves the synthesis of 3-hydroxy-3- methylglutaryl-CoA reductase (HMGCR).
    • This pathway is the core for multiple cellular metabolisms in eukaryotic, archaea, and some bacteria organisms, including cholesterol biosynthesis and protein.
    • Cholesterol is produced to build membrane cell structure, steroid hormones, myelin sheets in neuron system, precursors of vitamin D, formation and release of synaptic vesicles.
    • Mevalonic acid produces isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP).
    • These two main intermediates IPP and DMAPP set the ‘active isoprene’ unit as a basic building block of isoprenoid compounds.
    • Both of these units yield geranyl pyrophosphate (C10-monoterpenes) which further association with IPP produces farnesyl pyrophosphate (C15-sesquiterpenes).
    • Farnesyl pyrophosphate with one more unit of IPP develops into geranyl-geranyl pyrophosphate (C20-diterpenes).
    • The farnesyl pyrophosphate multiplies with its own unit to produce squalene, and its subsequent cyclization gives rise to cholesterols and other groups like triterpenoids.

    Vitamin E

    • Vitamin E refers to various forms of α-tocopherol.
    • Other tocopherol analogs exist, including B, y-, and S-tocopherols, but have lower vitamin E activity.
    • Plant oils, green vegetables, whole grains, egg yolks, and meats are rich dietary sources.
    • Wheat germ oil is a traditional natural source of vitamin E for therapeutic purposes.
    • Vitamin E is the major lipid-soluble antioxidant that protects cell membranes, proteins, and DNA from oxidation.
    • Deficiency can cause nerve and muscle damage, leading to loss of sensation and movement control, muscle weakness, and vision problems.
    • A weakened immune system is another sign of deficiency.

    Vitamin K

    • Vitamin K refers to 2-methyl-1,4-naphthoquinone and its derivatives.
    • Vitamin K1 (phytonadione, phylloquinone) is found in dairy products and fruits and vegetables, especially leafy greens.
    • The intestinal microflora also provide a significant portion of vitamin K.
    • Vitamin K is crucial for blood clotting (antihemorrhagic activity).
    • It is used to treat bleeding events caused by warfarin overdose.
    • Vitamin K helps in bone protein metabolism (osteocalcin), which binds to minerals for bone mineralization.
    • Deficiency results in hemorrhage, the most common symptom.

    Vitamin B1 (Thiamine)

    • Thiamine contains substituted pyrimidine, and thiazole rings linked by a methylene bridge.
    • It is stable in acidic environments but decomposes readily above pH 5.0.
    • About 50% of thiamine in foods is destroyed during cooking.
    • Whole grains, legumes, and meats are good thiamine sources.
    • Alcohol inhibits thiamine absorption.
    • Thiamine participates in energy metabolism, converting carbohydrates, lipids, and proteins into energy.
    • It plays a key role in nerve and muscle activity, and may be helpful for people with Alzheimer's disease.
    • Thiamine contributes to myelin sheath development and improves brain function.
    • Deficiency leads to various clinical syndromes, including Wernicke-Korsakoff syndrome and beriberi.

    Vitamin B2 (Riboflavin)

    • Riboflavin is a yellow, heat-stable substance, slightly soluble in water.
    • It is sensitive to light and decomposes into lumichrome or lumiflavin, depending on the acidity of the solution.
    • Yeast is the richest natural source, with dairy products, eggs, legumes, and meats also being important sources.
    • Riboflavin is stable during cooking in the absence of light.
    • Several coenzyme functions in oxidation-reduction reactions are necessary for energy release from carbohydrates, fats, and proteins.
    • Riboflavin stimulates growth and reproduction.
    • It plays a role in vision, conversion of other B vitamins, and acts as an antioxidant.
    • Deficiency can cause stomatitis and dermatitis.

    Vitamin B3 (Niacin)

    • Niacin prevents pellagra.
    • Niacinamide is also naturally occurring and has anti-pellagra activity.
    • Meats, fish, and dairy products are good sources of niacin.
    • Roasting coffee beans releases a significant amount of niacin.
    • Tryptophan is converted to niacin in the body.
    • Niacin acts as a coenzyme in energy-transfer reactions, similar to riboflavin, carrying hydrogen during metabolic reactions.
    • It protects against neurological degeneration and Alzheimer's disease.
    • Niacin helps lower LDL cholesterol, reduces the risk of cardiovascular diseases, and alleviates arthritis.
    • Deficiency leads to pellagra, characterized by symptoms affecting the nervous system, skin, and gastrointestinal tract (dementia, dermatitis, and diarrhea).

    Vitamin B5 (Pantothenic Acid)

    • Pantothenic acid, a component of the vitamin B complex, is known as the "chick anti-dermatitis factor".
    • Animal organs (heart, kidney, and liver) and cereal grains are rich in pantothenic acid.
    • Pantothenic acid helps turn food into energy.
    • It is involved in the synthesis of lipids, neurotransmitters, steroid hormones, and hemoglobin.
    • Pantothenic acid contributes to tissue and cell repair, wound healing, and normalizes blood lipid profiles.
    • Deficiency causes fatigue and sleep disturbances.

    Vitamin B6

    • Vitamin B6 refers to pyridoxol, pyridoxal, and pyridoxamine, which are highly substituted pyridine derivatives with similar physiologic activity.
    • Pyridoxine predominates in plant materials, while pyridoxal and pyridoxamine are found in animal tissues.
    • Synthetic pyridoxine is commonly used for dietary supplementation and therapeutic purposes because it is the most stable form.
    • Beef liver, tuna, salmon, fortified cereals, chickpeas, poultry, and some fruits and vegetables (especially dark leafy greens, pineapple, papaya, oranges, and cantaloupe) are good sources.
    • Vitamin B6 is required for various biological reactions, including amino acid metabolism, neurotransmitter synthesis, and red blood cell formation.
    • It acts as a cofactor for a diverse range of biochemical reactions regulating cellular metabolism.
    • Deficiency causes peripheral neuropathy, with symptoms similar to niacin and riboflavin deficiencies, including neurological abnormalities, skin lesions, and hypochromic microcytic anemia.

    Vitamin B7 (Biotin)

    • Eggs, fish, meat, seeds, nuts, and certain vegetables (such as sweet potatoes) contain high levels of biotin.
    • Biotin transfers carbon dioxide in metabolic reactions.
    • Biotin is essential for the breakdown of carbohydrates, fats, and proteins into energy.
    • It plays a crucial role in cellular reactions, particularly fat and protein metabolism in hair roots, fingernails, and skin.
    • Biotin is involved in fatty acid synthesis.
    • Deficiency causes fatigue, depression, and dermatitis.

    Vitamin B9 (Folate)

    • Folate is essential for brain development and function.
    • It aids in the production of DNA and RNA, and plays a crucial role in the metabolism of vitamins and amino acids.
    • It is crucial during pregnancy to prevent birth defects.
    • Folate is required for the synthesis of glycine, methionine, thymine, and uracil.
    • Deficiency leads to megaloblastic and macrocytic anemias and glossitis.

    Vitamin B12 (Cobalamin)

    • Vitamin B12 refers to a series of porphyrin-related corrinoid derivatives that function as extrinsic factors to prevent pernicious anemia.
    • Cyanocobalamin, a red crystalline material, is the most stable form and is frequently used in therapy.
    • Hydroxocobalamin, with a hydroxyl group instead of the cyano group, also has therapeutic applications.
    • Vitamin B12 acts as a coenzyme in the conversion of homocysteine to methionine.
    • It plays a role in the metabolism of fatty acids and amino acids, the production of neurotransmitters, and maintains the protective lining around nerve fibers.
    • Vitamin B12 is essential for bone cell activity and DNA synthesis.
    • It contributes to brain function and red blood cell synthesis.
    • Deficiency typically affects rapidly dividing cells of the hematopoietic system (leading to megaloblastic anemia) and causes irreversible neurological damage (due to defective myelin sheaths).
    • Symptoms include irritability, weakness, memory loss, mood swings, and tingling or numbness in the limbs.

    Vitamin C

    • Vitamin C, also known as L-ascorbic acid, is a naturally occurring vitamin that prevents scurvy and has antioxidant properties.
    • Vitamin C exists in equilibrium with dehydro-L-ascorbic acid, its oxidized form, which also exhibits antiscorbutic activity.
    • Vitamin C is the least stable of all vitamins.
    • Good sources of Vitamin C include citrus fruits, tomatoes, strawberries, and other fresh fruits and vegetables.
    • Freezing preserves Vitamin C content, but cooking can result in up to 50% loss.
    • Vitamin C plays an important role in various processes, including:
      • Antioxidant activity
      • Enzyme activation and oxidative stress reduction
      • Collagen synthesis and iron absorption
      • Defense against infections and inflammation
    • Vitamin C deficiency leads to scurvy.

    Glycosides

    • Glycosides are organic compounds, typically found in plants, composed of a sugar portion (glycon) linked to a non-sugar moiety (aglycone or genin) by a glycosidic bond.
    • There are four main classes of glycosides: C-glycosides, O-glycosides, S-glycosides, and N-glycosides.
    • Glycosides can be hydrolyzed by enzymes or acids, generating one or more sugars.
    • Sugars in glycosides exist in isomeric α and β forms, with the β-form being prevalent in plants.
    • α and β anomers differ in the configuration of the hydroxyl group on the anomeric carbon (C-1).
    • Chemically, glycosides are acetals formed by condensation of the glycon's hydroxyl group (OH) with the aglycone's hydroxyl group.
    • Glycones provide solubility properties for absorption and distribution in the body, while aglycones are responsible for pharmacological activity.

    Physical and Chemical Properties of Glycosides

    • Due to their complex structures, generalisations about their stability are not possible.
    • Solubility: Most glycosides are soluble in water or hydroalcoholic solutions, but insoluble or less soluble in non-polar organic solvents. The sugar moiety contributes to water solubility. Aglycones are soluble in non-polar solvents like benzene, ether, and chloroform.
    • Stability and hydrolytic cleavage:
      • Acids and alkali: Glycosides can be hydrolyzed by heating with dilute acids, cleaving the glycosidic linkages. They are relatively stable in alkalis.
      • Enzyme hydrolysis: Specific enzymes, usually found in the same plant but in separate compartments, can specifically hydrolyze glycosides. The same enzyme can hydrolyze different glycosides, but α and β stereoisomers are typically hydrolyzed by different enzymes.
    • Shape: Glycosides are solid, amorphous, and non-volatile.
    • Color: Glycosides are generally colourless except for flavonoids (yellow) and anthraquinones (red or orange).
    • Taste: Most glycosides are bitter.
    • Odor: Glycosides are odorless except for saponins (glycyrrhizin).

    Importance of Glycosides

    • Glycosides play significant roles in plant life and are involved in various functions:
      • Sugar reserves
      • Waste products of plant metabolism
      • Detoxification
      • Osmotic regulation
      • Regulation of metabolic substances
      • Defense against microorganisms (aglycones can act as antiseptics and bactericides).
    • Many therapeutic agents are derived from glycosides, contributing to various therapeutic classes:
      • Cardiac glycosides: Examples include digitalis, strophanthus, squill, etc.
      • Laxative drugs: Senna, aloe, rhubarb, cascara sagrada, and frangula contain emodin and other anthraquinone glycosides.
      • Sinigrin: From black mustard, yields allyl isothiocyanate, a potent local irritant.

    Classification of Glycosides

    • According to the type of glycosidic linkage:

      • α-glycosides: The glycone is an α sugar.
      • β-glycosides: The glycone is a β sugar.

    • According to the chemical group of the aglycone involved:

      • O-Glycosides: Aglycone-O-sugar (OH group): Examples include senna and rhubarb.
      • C-Glycosides: Aglycone-C-sugar (C-group): Example is cascaroside from cascara.
      • S-Glycosides: Aglycone-S-sugar (SH-group): Example is sinigrin from black mustard.
      • N-Glycosides: Aglycone-N-sugar (NH-group): Example is glycoalkaloid.

    • According to the chemical nature of the aglycone:

      • Cardioactive group
      • Anthraquinone group
      • Saponin group
      • Cyanophore group
      • Isothiocyanate group
      • Flavonol group
      • Alcohol group
      • Aldehyde group
      • Phenol group

    • According to the nature of the simple sugar component:

      • Glucoside: The glycone is glucose.
      • Galactoside: The glycone is galactose.
      • Mannoside: The glycone is mannose.
      • Arabinoside: The glycone is arabinose.

    Biosynthesis of Glycosides

    • Biosynthetic pathways vary depending on the aglycone and glycone units.
    • Aglycone and sugar parts are synthesized separately and then coupled.
    • Coupling involves phosphorylation of a sugar to generate a sugar 1-phosphate, which reacts with a uridine triphosphate (UTP) to form a uridine diphosphate sugar (UDP-sugar) and inorganic phosphate.
    • This UDP-sugar reacts with the aglycone to form the glycoside and a free UDP.

    Extraction of Glycosides

    • Plants containing glycosides also contain specific hydrolyzing enzymes. These enzymes must be inactivated by boiling the plant in water or alcohol.
    • Defatting or purification of the plant material is necessary, especially for seeds.
    • Treatment with lead acetate precipitates tannins and other non-glycosidal impurities.
    • Excess lead acetate is removed by passing hydrogen sulfide (H2S) gas through the solution.
    • The extract is filtered and concentrated to yield a crude glycoside.
    • The crude glycoside is purified by chromatography or crystallization.

    Cardioactive Glycosides

    • This group is characterized by their specific action on cardiac muscle, increasing tone, excitability, and contractility.
    • The aglycones of these glycosides are known as "cardiac genin," which are steroidal in nature, derived from cyclopentaphenanthrene and containing an unsaturated lactone ring attached to C17.

    Structure of Glycosides

    • Two types of genin can be distinguished based on the size of the lactone ring:
      • Cardenolides (e.g., digitoxigenin): Possess a five-membered lactone ring.
      • Bufanolides or bufadienolides (e.g., scillarenin): Possess a six-membered lactone ring.
    • The lactone ring determines the reaction to certain color tests.

    Cardenolides

    • In cardenolides (23 carbons), the lactone ring attached to C17 is a butenolide (4 carbons), which is also known as an α,β-unsaturated lactone ring.
    • Examples include the glycosides from Digitalis and Strophanthus species.

    Scilladienolides (Bufadienolides)

    • In scilladienolides (24 carbons), the lactone ring attached to C17 is a pentadienolide (5 carbons with two double bonds), also called a pentenolide.
    • Examples include squill glycosides and Bufotoxin.

    The Glycone Portion

    • The glycone portion at position C-3 of cardiac glycosides can contain up to four monosaccharide molecules linked in series.
    • Thus, from a single genin, one can have a monoside, bioside, trioside, or tetroside.

    Structural Features of Cardioactive Glycosides

    • All cardioactive glycosides share these key features:
      • A β-OH group at position C-3, involved in a glycosidic linkage to a mono, di, tri, or tetrasaccharide.
      • Another β-OH group at C-14.
      • An unsaturated 5 or 6-membered lactone ring at position C-17, also in the β configuration.
      • Additional OH groups may be present at C-5, C-11, and C-16.

    Nomenclature of Cardioactive Glycosides

    • The following sequence is used for naming these glycosides:
      • Functional groups are listed and their configuration is denoted.
      • The α or β configuration is specified.
      • The glycoside type is indicated.
      • The position of double bonds is denoted.

    Biosynthesis of Cardioactive Glycosides

    • Most knowledge of steroid biosynthesis comes from studies of cholesterol production.
    • Aglycones of cardiac glycosides are derived from mevalonic acid, but the final molecules arise from a condensation of a C21 steroid with a C2 unit (this unit provides C-22 and C-23).
    • Bufadienolides are condensation products of a C21 steroid and a C3 unit.

    Drugs Containing Cardioactive Glycosides

    1- Digitalis (Foxglove)

    • Dried leaf of Digitalis purpurea; F: Scrophulariaceae.
    • The name "digitalis" comes from the Latin "digitus," meaning finger, referring to the finger-shaped corolla. "Purpurea" is Latin and refers to the purple color of the flower.
    • Constituents:
      • The drug contains numerous glycosides, the most important medicinally are:
        • Digitoxin, gitoxin, and gitaloxin.
        • Average concentration is about 0.16%.
      • Nearly 30 other glycosides have been identified, such as purpurea glycosides A, purpurea glycoside B, gluco-gitaloxin, and gluco-digitoxigenin.
      • Primary glycosides with acetylated sugar moieties.

    Digitalis lanata

    • Nearly 70 different glycosides have been found in the leaves of Digitalis lanata.
    • All are derivatives of five different aglycones, three of which (digitoxigenin, gitoxigenin, and gitaloxigenin) also occur in Digitalis purpurea.
    • The other two types of glycosides are derived from digoxigenin and diginatigenin, found in Digitalis lanata but not Digitalis purpurea.
    • The leaves are used as a source of the glycosides digoxin and lanatoside C.

    2- Strophanthus

    • Dried ripe seeds of Strophanthus kombe or Strophanthus hispidus; F: Apocyanaceae.
    • Principal glycosides are K-strophanthoside, K-strophanthin-B, and cymarin, all based on the genin strophanthidin.
    • Constituents:
      • K-strophanthoside (also known as strophoside): The main glycoside in both S. kombe and S. hispidus. Composed of the genin strophanthidin coupled to a trisaccharide consisting of cymarose, β-glucose, and α-glucose.
      • Strophanthin: Used intravenously (I.V.) as a cardiotonic.
      • Ouabin (G-strophanthin): Obtained from S. grantus (F: Apocynaceae). Acts as a cardiotonic administered I.V. for rapid therapeutic effects. Oral administration is not recommended or safe because of slow and irregular absorption.

    3- Oleander

    • The leaves of Nerium oleander (F: Apocynaceae) have been used historically to treat cardiac insufficiency.
    • The main constituent is oleanderin, which is considered a promising agent for anticancer treatment.
    • Oleander has been viewed as poisonous due to the potential toxicity of some of its compounds, especially when consumed in large amounts by animals.

    4- (Bufadienolide) Squill

    • The bulb of the white variety of Urginea maritima, known as white or Mediterranean squill, or of Urginea indica, known in commerce as Indian squill; F: Liliaceae.
    • The genins of squill glycosides differ from those of cardenolides in two key aspects:
      • They have a six-membered doubly unsaturated lactone ring at position C-17.
      • They have at least one double bond in the steroid nucleus.
    • Uses: As an expectorant, it also has emetic, cardiotonic, and diuretic properties.
    • Red squill (from the red variety of Urginea maritima) is mainly used as rat poison.

    Mechanism of Action of Cardioactive Glycosides

    • They inhibit the Na+/K+ ATPase enzyme (membrane-bound enzyme) which helps maintain cell membrane ion gradients (K+ inside the cell and Na+ outside), by inhibiting the enzyme the transport of K+ back into the cell is blocked and its concentration in the extracellular fluid increases, at the same time, Na+ ions enter the cell promoting the entry of Ca+2 which are essential for muscle contraction.
    • This leads to increased intracellular calcium concentration, which promotes muscle contraction.
    • They are commonly used to treat congestive heart failure.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Biosynthetic Pathways of Secondary Metabolites PDF

    Description

    This quiz covers the mechanisms of action for cardiac glycosides, their metabolites, and the role of various vitamins in the body. It also addresses important concepts in photosynthesis and the citric acid cycle. Test your knowledge on these fundamental topics in pharmacology and biochemistry.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser