Basic metabolic pathways.pptx

Metabolic pathways

1. BASIC METABOLIC PATHWAYS

2. Metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites. Pathways are required for the maintenance of homeostasis within an organism and the flux of metabolites through a pathway is regulated depending on the needs of the cell and the availability of the substrate. Metabolic pathways can be classified as Energy utilizing (anabolic) Energy generating (catabolic) Catabolic pathway: A catabolic pathway is an exergonic system that produces chemical energy in the form of ATP, GTP, NADH, NADPH, FADH2, etc. from energy containing sources such as carbohydrates, fats, and proteins. The end products are often carbon dioxide, water, and ammonia. Anabolic pathways: These require an energy input to construct macromolecules such as polypeptides, nucleic acids, proteins, polysaccharides, and lipids.

3. The building blocks for secondary metabolites are derived from primary metabolism. Metabolites from photosynthesis, glycolysis, and the Krebs cycle are tapped off from energy-generating processes to provide biosynthetic intermediates. The most important building blocks used in the biosynthesis of secondary metabolites are derived from the intermediates acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid, and 1-deoxyxylulose 5-phosphate. These are utilized respectively in the acetate, shikimate, mevalonate, and deoxyxylulose phosphate pathways. In addition to acetyl-CoA, shikimic acid, mevalonic acid, and deoxyxylulose phosphate, other building blocks based on amino acids are frequently employed in natural product synthesis. Living plants are solar-powered biochemical and biosynthetic laboratory which manufactures both primary and secondary metabolites from air, water, minerals and sunlight. The primary metabolites like sugars, amino acids & fatty acids that are needed for general growth & physiological development of plant which distributed in nature & also utilized as food by man. The secondary metabolites such as alkaloids, glycosides, Flavonoids, volatile oils etc. are biosynthetically derived from primary metabolites.

4. SHIKIMIC ACID PATHWAY

5. Shikimic acid Commonly known as its anionic form shikimate , is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi the Japanese star anise, Illicium anisatum ), from which it was first isolated in 1885 by Johan Fredrik Eykman . The elucidation of its structure was made nearly 50 years later. Shikimic acid is also the glycoside part of some hydrolysable tannins. The shikimate pathway is a seven step metabolic route used by bacteria, fungi, algae, parasites, and plants for the biosynthesis of aromatic amino acids ( phenylalanine, tyrosine, and tryptophan ). This pathway is not found in animals; therefore, phenylalanine and tryptophan represent essential amino acids that must be obtained from the animal's diet Animals can synthesize tyrosine from phenylalanine, and therefore is not an essential amino acid except for individuals unable to hydroxylate phenylalanine to tyrosine).

6. Shikimic Acid Pathway

7. Shikimic acid pathway starts with the precursors, Erythrose 4-phosphate and Phosphoenolpyruvate coupling to form 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP). Reaction catalysed by phospho-2-oxo-3-deoxyheptonate aldolase. The enzyme, 3 - dehydroquinate synthase, catalysing the cyclization of DAHP to 3-dehydroquinic acid, (DHQ). It requires cobalt (II) and nicotinamide adenine dinucleotide (NAD) as cofactors.

8. Prephenic acid is then synthesized by a Claisen rearrangement of chorismate by Chorismate mutase. P r ep h en a te i s o x id a t i ve l y decarboxylated with retention of th e h y d ro x y l g r o up by P rephe n ate de h ydr o genase to gi v e p- hydroxyphenylpyruvate , which is transaminated using gl u tamat e as th e nitrog e n so u r ce to gi v e t y r o si n e a n d α- ketoglutarate .

9. The formation of chorismic acid is an important branch point in the shikimic acid pathway as this compound can undergo three different types of conversion. In the presence of glutamine, chorismic acid is converted to anthranilic acid, whereas chorismate mutase catalyses the formation of prephenic acid. Chorismic acid is also converted into p-aminobenzoic acid. Then after anthranilic acid is converted first to phosphoribosyl anthranilic acid and then to carboxyphenylaminodeoxyribulose-5-phosphate, these reactions being catalysed by anthranilate phosphoribosyl transferase and phosphoribosyl anthranilate isomerase, respectively. Ring closure to form indolyl-3-glycerol phosphate is catalysed by indolyl-glycerol phosphate synthase. The enzyme catalysing the final reaction, that is, tryptophan synthase consists of two components; component A catalyses the dissociation of indolylglycerol phosphate to indole and glyceraldehydes-3-phosphate, whereas component B catalyses the direct condensation of indole with serine to form tryptophan.

10. Tyrosine and phenylalanine are both biosynthesized from prephanic acid, but by independent pathways, which act as a precursor for the biosynthesis of phenylpropanoids. The phenylpropanoids are then used to produce flavonoids, coumarins, lignin and tannins. In the formation of tyrosine, prephanic acid is first aromatized to 4-hydroxyphenylpyruvic acid, a reaction catalysed by prephenate dehydrogenase. Transamination, catalysed by tyrosine aminotransferase, then gives tyrosine. The biosynthesis of phenylalanine involves first the aromatization of prephanic acid to phenyl pyruvic acid, a reaction catalysed by prephenate dehydratase, and then transamination catalysed by phenylalanine aminotransferase, which gives phenylalanine.

11. Uses / Role of Shikimic Acid Pathway: Starting Point in t he Biosynthesis of Some Phenolics Phenyl alanine and tyrosine are the precursors used in the biosynthesis of p he n y lp r opa n o i d s . Th e p he n y lp r opa n o i d s a r e then u sed t o p r oduc e t h e flavonoids, coumarins, tannins and lignin. Gallic acid biosynthesis : Gallic acid is formed from 3-dehydroshikimate by the action of the enzyme shik i ma t e d e h y dro ge n a s e t o p r oduc e 3,5 - did e h y dro s hik i ma t e . T he l a t t er compound spontaneously rearranges to gallic acid. Shikimic acid is a precursor for: indole, indole derivatives and aromatic amino acid tryptophan and tryptophan derivatives such as the psychedelic compound dimethyltryptamine. many alkaloids and other aromatic metabolites. In the pharmaceutical industry, shikimic acid from the Chinese star anise ( Illicium verum ) is used as a base material for production of oseltamivir ( Tamiflu ). Shikimate can be used to synthesize ( 6S)-6-Fluoroshikimic acid, an antibiotic which inhibits the aromatic biosynthetic pathway.

12. MEVALONIC ACID PATHWAY

13. Mevalonic acid is a precursor in the biosynthetic pathway known as the mevalonate  pathway that produces terpenes and steroids.  Mevalonic acid is the primary precursor of isopentenyl pyrophosphate (IPP), that is in turn the basis for all terpenoids . The  mevalonate pathway, also known as the  isoprenoid pathway or HMG- CoA reductase pathway is an essential  metabolic pathway  present in  eukaryotes ,  archaea , and some  bacteria . The pathway produces two five-carbon building blocks called  isopentenyl pyrophosphate  (IPP) and  dimethylallyl pyrophosphate  (DMAPP), which are used to make  isoprenoids , a diverse class of over 30,000 biomolecules such as  cholesterol ,  vitamin K ,  coenzyme Q10 , and all  steroid hormones . The mevalonate pathway begins with  acetyl- CoA  and ends with the production of IPP and DMAPP. It is best known as the target of  statins , a class of cholesterol lowering drugs. Statins inhibit  HMG- CoA reductase  within the mevalonate pathway.

14. The pathway begins with acetyl CoA molecule produced from pyruvic acid, which is the end product of glycolysis. First 2 molecules of acetyl CoA forms acetoacetyl CoA through Claisen condensation. 3 rd molecule of acetyl CoA forms β- hydroxy β- methylglutaryl -CoA by aldol addition. Next on reduction gives rise to mevalonic acid, which is the main precursor for biosynthesis of terpenoids. Mevalonic acid on ATP mediated phosphorylation gives mevalonic acid diphosphate which on decarboxylation gives the 1st isoprene unit, isopentyl pyrophosphate (IPP). By the isomerase enzyme, the IPP gives 2nd isoprene unit Dimethyl allyl pyrophosphate (DMAPP) Electrophilic addition of IPP with DMAPP via enzyme prenyl transferase yield C10 unit, geranyl pyrophosphate (GPP), which is the precursor for synthesis of monoterpenes. Steps Involved

15. Combinations of another IPP unit with GPP give rise to form farnesyl pyrophosphate (FPP), C15 unit which acts as a precursor for the synthesis of sesquiterpene. Further addition of IPP unit gives C20 geranyl geraniol pyrophosphate (GGPP) to produce a range of Diterpenes On further addition of IPP unit gives C25 geranyl farnesyl pyrophosphate called Sesterterpenes . The tail to tail addition of two FPP units yields C30 unit, triterpene. Similarly 2 units of GGPP yield C40 unit, tetraterpene. The acetate mevalonate pathway thus works through IPP and DMAPP via squalene to produce two different skeleton containing compounds, that is, steroids and triterpenoids. It also produces vast range of monoterpenoids, sesquiterpenoids, diterpenoids, carotenoids, polyprenols , and also the compounds like glycosides and alkaloids in association with other pathways

16. 7 Isopentyl Diphosphate: The Biological Isoprene Unit. Mevalonic acid is the biosynthetic precursor to the actua l C 5 “isoprene units,” which are isopentyl diphosphate (IPP, tail) and dimethylallyl diphosphate (DMAPP, head) H 2 C SC o A O C O O S C o A H O 2 C H 3 C O H O 3 -H ydroxy-3 -m ethylglutaric acid (H M G -C o A ) HM G-Co A reductase 2 N A D PH O H H O 2 C H 3 C O H M evalonic acid O B : acetyl C o A B H aldol con d ensa t i o n HM G-Co A synthase H 2 C C SC o A H SC o A acetoacetyl C o A O H 2 C C S C o A H B : O C H 2 C S C o A acetyl C o A O O C la ise n conde nsation S C o A a ce toacetyl C o A O H 3 C C S -C ys - E n zym e a cetyl C o A acetoacetyl-C o A acetyltransferase O H 3 C C S C o A E nzym e-C ys-S H

17. Conversion of mevalonic acid to IPP and DMAPP O H H O 2 C H 3 C O H M evalonic acid A T P A M P O - O O O P O P O - O - O O H 3 C O H H rearrangm ent O - O - O O P O O - H dim ethylallyl-PP (D M A P P ) isopentenyl-P P (IP P) B : H + A TP A D P 2 - 3 O P O 3 - O O O P O P O O - O - O O H C H O - O O O P O P O - O - H H B : C H 3 O - O O O P O P O - O - O O H 4 - P O 3 - Carbon-Carbon Bond Formation in Terpene Biosynthesis. Conversion of IPP and DMAPP to geraniol-PP and farnesyl-PP e l ec t r o p hilic head group nu c l e o p hilic tail group e l ec t r o p hilic head group nu c l e o p hilic tail group O P P O P P H H O P P O P P B : D M A P P IP P - O P P M g 2 + O P P O P P H H B : O P P 1 5 f a r n e s y l p y r opho s ph a t e ( C ) geranyl pyrophosphate (C 10 ) - O P P M g 2 +

18. 9 O P P P P O s q u a l e n e synthase Conversion of genanyl-PP to monoterpenes Limonene & -Terpineol O P P O P P geranyl diphosphate neryl diphosphate O PP - H + H : B H O H 2 O C=C bond acts as a nucleophile - t erpineol limonene

19. ACETATE MALONATE PATHWAY

20. Acetate-Malonate Pathway Acetate-Malonate pathway includes synthesis of fatty acids and aromatic compounds with the help of secondary metabolites. Main precursors of Acetate-Malonate Pathway are Acetyl-CoA and Malonyl-CoA. End product of this pathway can be saturated or unsaturated fatty acids or polyketides. Polyketides are secondary metabolites which further synthesize aromatic compounds by Polyketide Pathway.

21. Precursors Acetyl-CoA : Starter Unit Malonyl-CoA : Extender Unit

22. Acetate-Malonate Pathway

23. Amino acid Pathway

24. Plants and bacteria can synthesize all 20 of the amino acids. Whereas humans cannot synthesize 9 of them. These 9 amino acids must come from the diets and are called essential amino acids. The essential amino acids are Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine. The 11 amino acids are called non-essential amino acids like Alanine, Arginine, Aspargine , Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine and Tyrosine. The non-essential amino acids are synthesized by simple pathways, whereas biosynthesis of the essential amino acids are complex.