Biosynthetic Pathways PDF

General biosynthetic pathways Dr. Mosa E. O. Ahmed 11/17/2024 Dr. Mosa E. O. Ahmed 1  Biosynthesis of primary and 2nd metabolites is dependent on highly organized structure of the plant and animal cell. Some basic metabolic pathways are similar...

General biosynthetic pathways Dr. Mosa E. O. Ahmed 11/17/2024 Dr. Mosa E. O. Ahmed 1  Biosynthesis of primary and 2nd metabolites is dependent on highly organized structure of the plant and animal cell. Some basic metabolic pathways are similar in both animal and plant cell. Production of 2nd metabolites is dependent on basic metabolic cycles in living tissues including: Photosynthesis Embden-Meyerhoff scheme of glycolysis TCA cycle 11/17/2024 Dr. Mosa E. O. Ahmed 2 What are the differences between animal and plant cells? Plant cell has rigid cell wall. In plant cell, connection between adjacent cells maintained by primary pits Plant cell has chloroplast and vacuoles. 11/17/2024 Dr. Mosa E. O. Ahmed 3 Representative Plant Cell 11/17/2024 Dr. Mosa E. O. Ahmed 4 What are Plant 2nd metabolites? Are organic compounds synthesized to aid plant survival. Are not directly involved in the normal growth, development or reproduction of an organism. They usually have ecological function: (Responsible for odor, pungency, color, culinary, medicinal or poisonous Values). Include glycosides, aromatic compounds (flavonoids, anthraquinones, tannins), isoprenoid (mono-, di- and triterpenes), etc. 11/17/2024 Dr. Mosa E. O. Ahmed 5 Production of 2nd metabolites Some basic metabolic pathways are similar in animal and plant cells. Production of 2nd metabolites is depend on basic metabolic cycles of living tissues. Biosynthesis of 2nd metabolites is an enzyme-depend reaction. 11/17/2024 Dr. Mosa E. O. Ahmed 6 Enzymes Enzymes are organic catalyst produced by plant and animal cells. Enzymes are colloidal in nature and consist of protein or contain proteins as essential pa. They have high molecular weight. Are soluble either in water or dilute salt solution. Are precipitated by acetone, alcohol and high salt concentration. They are inactivated by heat, UV light and X-ray. 11/17/2024 Dr. Mosa E. O. Ahmed 7 Enzymes It acts on one substance or class of substances (it is specific for pa icular atomic group or linkage). Their specificity is varies (lipase is not highly specific, while fumarase act only upon fumarate and L- malate). 11/17/2024 Dr. Mosa E. O. Ahmed 8 Enzymes Coenzymes are small organic molecules required for the action of enzymes. One group of coenzyme consist of esters of phosphoric acid and various nucleosides. e.g. Adenosine triphosphate (ATP) = high energy phosphate bond Uridine triphosphate (UDP) = synthesis of sucrose Nicotinamide-adenine dinucleotide (NAD) = oxidation- reduction reaction Coenzyme A (coA) = activate acetate Flavin mononucleotide (FMN) = oxidation-reduction reaction Flavin adenine dinucleotide (FAD) = transfer (H) ion from NADH to oxidized cytochrome system. Thiamine, biotin and pyridoxine 11/17/2024 = decarboxylation Dr. Mosa E. O. Ahmed 9 Enzymes Enzymology of 2nd metabolic pathways is still li le investigated. But advances in gene technology pave the way for studying enzymology of 2nd metabolites. Cell cultures are be er source for isolation of enzymes (i.e. useful for preparation and manufacturing of enzymes). Enzymes are isolated by the methods of protein chemistry (gel and affinity chromatography, dialysis). 11/17/2024 Dr. Mosa E. O. Ahmed 10 Classification of enzymes Class Function and examples 1. Esterase hydrolyse chlorophyll (Chlorophyllase) hydrolyze fats (Lipases) 2. Oxidoreductase Conve phenolic substances to quinones Catalysis decomposition of hydrogen peroxide (Catalase) 3. Hydrolases Hydrolysing esters (hydrolyse triglycerides, sugars and glycosides). e.g. tannase, amylase, cellulase, inulase, B-glucosidase. Hydrolysing C-N linkage (e.g. in animal: pepsin, renin, plasmin. E.g. in plant: papain and ficin). 4. Layase Biosynthesis of indole alkaloids (Tryptophan decarboxylase, (decarboxylase) tyrosine decarboxylase) 5. Isomerases Biosynthesis of terpenoids (IPP-isomerase and chalcone 11/17/2024 isomerase) Dr. Mosa E. O. Ahmed 11 Photosynthesis Photosynthesis is a process by which plant, algae and some bacteria conve carbon dioxide into organic compounds. Divided into two steps: Light reaction. Dark reaction (light independent) 11/17/2024 Dr. Mosa E. O. Ahmed 12 Photosynthesis Light reaction consist of two processes (both of them require light): 1. production of ATP from ADP →energy 2. light-energized decomposition of water (Hill reaction). Hill reaction: 2H2O+2A+(light)→2A[H]+O2 A: electron acceptor (plastoquinone coenzyme) Hydrogen atoms transferred NADP*coenzyme to reduce carbon 11/17/2024 dioxide in dark reaction. Dr. Mosa E. O. Ahmed 13  Calvin-Benson Cycle. Known as dark reaction. In several steps, Glyceraldehyde 3-phosphate forms fructose and erythrose. From fructose; glucose, sucrose and starch are derived. From Erythrose: aromatic acids are derived. 11/17/2024 Dr. Mosa E. O. Ahmed 14  Depending on the first cpd produced in dark reaction plant classified into: C3- plants: first compound produced is 3- phosphoglyceric acid. C4-plants:first compound is oxaloacetic acid and other C4-acids. These plants grow in semi-arid and high light intensity conditions. CAM plants (Crassulacean Acid Metabolism): first compound is malic acid (C4-dicarboxlic). 11/17/2024 Dr. Mosa E. O. Ahmed 15 Carbohydrates utilization The pathway for metabolism of glucose is known as Embden- Meyerhoff scheme of glycolysis. Carbohydrates (CHO) stored in plants as starch and in animal as glycogen. CHO used for energy production by process which involve conversion to pyruvate then acetate. Active acetate inter TCA cycle. 11/17/2024 Dr. Mosa E. O. Ahmed 16 Carbohydrates utilization In TCA cycle, CHO oxidized to water and carbon dioxide. During this process, hydrogen is liberated and carried by coenzyme (NAD) to cytochrome system to produce ATP from ADP. In this pathway, one molecule of glucose gives two molecules of pyruvate each of which is conve ed to acetate and one molecule of carbon dioxide. 11/17/2024 Dr. Mosa E. O. Ahmed 17 Carbohydrates utilization In one turn of TCA, one acetate oxidized to two molecules of carbon dioxide and twelve molecules of ATPs. The overall reaction for the metabolism of one molecule of glucose: 11/17/2024 Dr. Mosa E. O. Ahmed 18 Relation between 2 metabolites and basic nd metabolic pathways Basic metabolic pathways are including: Photosynthesis Embden-Meyerhoff scheme of glycolysis TCA cycle They are basic schemes for building up and breakdown of reserve food and also for biosynthesis of secondary metabolites. 11/17/2024 Dr. Mosa E. O. Ahmed 19 11/17/2024 Dr. Mosa E. O. Ahmed 20  Flow cha of some cell metabolites 11/17/2024 Dr. Mosa E. O. Ahmed 21  Origin of secondary metabolites The most impo ant building blocks employed in the  biosynthesis of natural metabolites are derived from: Acetyl coenzyme A (acetyl- CoA) 1. 2. Shikimic acid 3. Mevalonic acid 4. 1- deoxy xylulose 5-phosphate 5. Amino acids 11/17/2024 Dr. Mosa E. O. Ahmed 22  1. Acetate (polyketides or fa y acids) pathway:  Occur in all organisms.  Biosynthesis begin with condensation of one molecule malonyl-CoA with one molecule of acetate-CoA to form simple polyketide acetoacetyl-CoA.  Generate large group of impo ant compounds:  Antibiotics (tetracyclines and macrolides)  Fa y acids  Aromatic cpds (anthracyclic antitumor agent) 11/17/2024 Dr. Mosa E. O. Ahmed 23  It was discovered as a pa of screening programme of extract obtained from filamentous bacteria (Actinomycetes) -It has numerous functional groups: te iary amine, amide group, hydroxyl, phenolic and keto groups. - the lower oxygenated carbons indicating that the precursor of this cpd is poly -β- keto ester. 11/17/2024 Dr. Mosa E. O. Ahmed 24 2. Shikimate pathway Shikimic acid is produced 3. Aromatic aldehydes (vanillin & from a combination of benzaldehyde) phosphoenolpyruvate (a 4. A number of cpd groups can glycolytic pathway be constructed from the amino intermediate) and erythrose 4 acid phenylalanine such as: -phosphate from the pentose phenylpropenes. phosphate pathway. Lignans Coumarins It is a precursor for: flavonoids 1. Aromatic amino acids All of them possess including phenylalanine, substructure based on C6-C3 tyrosine, tryptophan units. 2. Simple aromatic acid Do not find in animals (benzoic and gallic acid) 11/17/2024 Dr. Mosa E. O. Ahmed 25 11/17/2024 Dr. Mosa E. O. Ahmed 26  Biosynthesis of Phenylpropenes They are biosynthesized by the oxidation of phenylalanine by the enzyme phenylalanine ammonia lyase, which through the loss of ammonia result in formation of cinnamic acid. include: Eugenol (antiseptic) anethole (antimicrobial) Myristicin (hallucinogenic) safrole 11/17/2024 Dr. Mosa E. O. Ahmed 27 Biosynthesis of Lignans Are low mol. wt. polymers. Cinnamyl alcohol is a common precursor of lignans. Podophyllotoxin is example of this group This class of cpd is common in: Hea wood. leaves resinous exudate of roots and bark. 11/17/2024 Dr. Mosa E. O. Ahmed 28 Biosynthesis of Coumarins Phenylalanine is the precursor for coumarins. They have a limited distribution in plant kingdom. they were found in plant families: Apiaceae Rutaceae Asteraceae Fabaceae Kellin is isocoumarin (chromone) natural product from Ammi visnaga and has activity as spasmolytic and vasodilator. 11/17/2024 Dr. Mosa E. O. Ahmed 29 Biosynthesis of flavonoids: Flavonoids are derived from a C6-C3 units (C6 from shikimic acid pathway) and a C3 unit (from the polyketide pathway). Naringin is a flavanone glycoside has bi er and astringent taste which occur in the peel of grapefruit (Citrus paradisi). Quercetin is a flavanol present in many food stuffs, is a strong antioxidant. 11/17/2024 Dr. Mosa E. O. Ahmed 30 11/17/2024 Dr. Mosa E. O. Ahmed 31 Biosynthesis of Tannins They are water soluble polyphenolic cpds that have a high mol.wt. Broadly divided into two groups: Hydrolysable tannins (esterification of sugars with simple phenols such as gallic acid) Non-hydrolysable tannins (condensation of flavonoids) 11/17/2024 Dr. Mosa E. O. Ahmed 32 3. Mevalonate & Deoxyxylulose phosphate pathway  Mevalonic acid it self formed from three molecules of acetyl-CoA.  Deoxyxylulose phosphate arises from a combination of two glycolytic pathway intermediates, namely pyruvic acid and glyceraldehyde 3-phosphate. DOX route occur in plastids while mevalonate pathway in cytoplasm.  Both of them are responsible for the biosynthesis of a vast group of terpenes metabolites. 11/17/2024 Dr. Mosa E. O. Ahmed 33 Biosynthesis of Terpenes (isoprene) Known as isoprenes because the branched repeating C5 unit (isopentene) is similar to isoprene. Their precursor are dimethyallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP). Through isoprene rule. Include cpd. As : Menthol, camphor 11/17/2024 Dr. Mosa E. O. Ahmed 34 11/17/2024 Dr. Mosa E. O. Ahmed 35 5. Amino acids pathway  Amino acid are Constructed 1. Pyruvic acid → alanine from intermediates of 2. Oxaloacetic acid → aspa ic acid glycolytic pathway and the 3. α- ketoglutaric acid → glutamic acid. Krebs cycle. 4. Shikimic acid → aromatic amino Nitrogen inters organism acids (phenylalanine, tyrosine, and tryptophan). metabolism by reductive 5. 3- phosphoglycerate → serine & amination of α–keto acids glycine. THEY GROUPED INTO:  Many alkaloids and antibiotics are derived from amino acids. 11/17/2024 Dr. Mosa E. O. Ahmed 36 Biosynthesis of Alkaloids Amino acid precursors involved in alkaloids biosynthesis are: Ornithine - Histidine Lysine - Anthranilic acid Nicotinic acid - Tryptophan 11/17/2024 Dr. Mosa E. O. Ahmed 37 11/17/2024 Dr. Mosa E. O. Ahmed 38 Biosynthesis of Glycosides Are composed of pa s: Sugar Aglycone Aglycone may be a terpene, a flavonoid, a coumarin, etc. There are two basic classes of glycosides: C-glycosides (sugar is a ached through C-C bond) O-glycosides ( sugar is a ached through O-C bond). 11/17/2024 Dr. Mosa E. O. Ahmed 39  Impo ant group of glycosides: Cyanogenic glycosides anthraquinone glycosides cardiac glycosides glucosinolates 11/17/2024 Dr. Mosa E. O. Ahmed 40  The end 11/17/2024 Dr. Mosa E. O. Ahmed 41