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Showing 110281 - 110290 of 110297 pathways
PathBank ID Pathway Chemical Compounds Proteins

SMP0007031

Pw007889 View Pathway
Metabolite

Triacylglycerol Metabolism TG(14:0/15:0/28:0)

Saccharomyces cerevisiae
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. The biosynthesis of triacylglycerol is localized to the endoplasmic reticulum membrane and starts with glycerol 3-phosphate reacting with acyl-CoA through a glycerol-3-phosphate O-acyltransferase resulting in the release of lysophosphatidic acid (LPA). This, in turn, reacts with an acyl-CoA through a lipase complex resulting in the release of CoA and phosphatidic acid. Phosphatidic acid reacts with water through a phosphatidic acid phosphohydrolase 1 resulting in the release of a phosphate and a diacylglycerol. This reaction can be reversed through a CTP-dependent diacylglycerol kinase. The diacylglycerol reacts in the endoplasmic reticulum with an acyl-CoA through a diacylglycerol O-acyltransferase resulting in the release of coenzyme A and a triacylglycerol. Triacylglycerol metabolism begins with a reaction with water through lipase resulting in the release of a fatty acid, hydrogen ion, and a diacylglycerol. Diacylglycerol then reacts with a lipase 3 resulting in the release of a fatty acid and a monoacylglycerol. Monoacylglycerol reacts with monoglyceride lipase resulting in the release of a fatty acid in glycerol.

Metabolic

SMP0122633

Pw123948 View Pathway
Metabolite

Diterpenoid Biosynthesis

Arabidopsis thaliana
Diterpenes consist of four isoprene (organic hydrocarbon compound) units and are naturally synthesized in plants as metabolites. PathBank shows the gibberellin precursor biosynthesis pathway in cress, and some of those reactions appear in this pathway. A major intermediate of this pathway in thale cress is geranylgeranyl diphosphate (GGDP), which enters the cytosol via the terpenoid backbone biosynthesis subpathway to start diterpenoid biosynthesis, specifically of plant hormones, such as a number of gibberellins and their catabolites. Many of these enzymes use flavoproteins (for reduction/oxidation) and/or iron ions as their cofactors. The enzyme geranyllinalool synthase (EC 4.2.3.144) is a component of the herbivore-induced indirect defense system and catalyzes a reaction with GGDP whose product, (E,E)-geranyllinalool, is a precursor to the volatile compound 4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT), which is released by many plants in response to damage. GGDP can, using the enzyme ent-copalyl diphosphate synthase, create ent-copalyl diphosphate, which uses ent-kaur-16-ene synthase to create ent-kaurene. Aconitine and veatchine (both diterpenoid alkaloids derived from amination, although acontinine is more well-known as it is the plant toxin "monkshood" or that is known to induce arrhythmias by activating voltage-gated sodium channels) can form from ent-kaurene, although the specific reaction scheme for these formations is still unclear. Via ent-kaurene monooxygenase (often referred to misleadingly as ent-kaurene oxidase), an enzyme localized to the chloroplast outer membrane, three successive oxidations are catalyzed, converting ent-kaurene into first ent-16-kauren-19-ol, then ent-kaurenal, and then finally into ent-kaurenoate. At this point in the pathway, the reactions begin to take place in the endoplasmic reticulum membrane. Here, ent-kaurenoate oxidase (an enzyme localized to the endoplasmic reticulum outer membrane) catalyzes the conversion of ent-kaurenoate into gibberellin A12 via three successive oxidations: from ent-kaurenoate to ent-7-alpha-hydroxykaurenoate to ent-7alpha-Hydroxykaur-16-en-19-oic acid, which then in the final oxidation forms the product 6beta,7beta-Dihydroxykaurenoic acid; however, this acid, ent-7alpha-Hydroxykaur-16-en-19-oic acid, can also then use ent-kaurenoate oxidase again to form gibberellin A12 aldehyde. Gibberellin A12 aldehyde can form gibberellin A12 and gibberellin A53 aldehyde. Gibberellin A53 aldehyde forms gibberellin A53 in the cytosol. Here, gibberellin-44 dioxygenase (EC 1.14.11.12) is an oxidoreductase that catalyzes the conversion of gibberellin A12 and gibberellin A53 to gibberellin A9 and gibberellin A20 respectively, via a three-step oxidation at C-20 of the gibberellin A skeleton. Also in the cytosol exists a theoretical gibberellin-44 dioxygenase (a not yet elucidated enzyme), which catalyzes the reaction in the gibberellin biosynthesis pathway whereby gibberellin A12 becomes gibberellin A15 open lactone (also subsequently, gibberellin A24) and gibberellin A44 open lactone becomes gibberellin A19. Gibberellins A9 and A20 form A51 and A29 respectively, and gibberellin 2beta-dioxygenase (EC 1.14.11.13) catalyzes the formation of their catabolites. Gibberellin A20, via the cytosolic gibberellin 3-oxidase (an enzyme that requires ascorbic acid as a cofactor and is encoded by 4 differentially expressed genes (GA3ox1, GA3ox2, GA3ox3, GA3ox4) in thale cress), forms gibberellin A1, which in a reaction catalyzed by gibberellin 2beta-dioxygenase, forms gibberellin A8 and its catabolite. There are many offshoots in this pathway that are not described in detail or fully elucidated in Arabidopsis thaliana, but all assume a similar chain of reactions and ultimately result in the production of different gibberellin catabolites.

Metabolic

SMP0122665

Pw123981 View Pathway
Metabolite

Selenocompound Metabolism

Arabidopsis thaliana
The metabolism of selenium and its derived compounds begins with selenite, which enters plant cells through sulfate channels. Before it can enter the chloroplast to be further metabolised, with the help of thioredoxin reductase 2 it reacts with hydrogen ions to become hydrogen selenide, oxidizing NADPH in the process. Hydrogen selenide is then transported into the chloroplast, where it reacts with L-alanine and an oxidized electron acceptor to produce selenocysteine. This is then combined with O-succinyl-L-homoserine to produce selenocystathionine. Aided by cystathionine beta-lyase, selenocystathionine is then hydrolyzed and yields pyruvic acid and selenohomocysteine. After one more reaction involving 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase 2, selenomethionine is produced. This is a form in which selenium is commonly found in vascular plants and can be further metabolised for different uses. Diphosporic acid, S-methyl-methionine, and methylselenic acid are all produced from selenomethionine by different chemical reactions. Although selenium is not considered essential for many vascular plants, and may even be harmful at high concentrations, its presence has been shown to aid in a number of biological processes, such as photosynthesis and maintenance of general cell function.

Metabolic

SMP0122677

Pw123993 View Pathway
Metabolite

Ubiquinone Biosynthesis

Arabidopsis thaliana
Ubiquinone’s distinctive structure is defined by a polyisoprenoid side chain connected to a benzoquinone ring. It serves multiple roles in plants, functioning as an electron transporter in inner mitochondrial membranes, as well as acting as an antioxidant to protect against free radicals. The biosynthesis of ubiquinone is connected to the biosynthesis of tyrosine, tryptophan, and phenylalanine through the shared compounds L-tyrosine and chorismate. Its biosynthesis also takes place in many organelles, with key steps occurring in the mitochondria, chloroplasts, and peroxisomes of plant cells. The compound L-tyrosine begins in the cytoplasm and is converted to homogentisic acid before it can enter the chloroplast through the transporter homogentisate prenyltransferase. Once in the chloroplast, homogentisic acid can follow one of three different sets of reactions, ultimately forming five different compounds, plastoquinol-9, α-tocopherol, β-tocopherol, α-tocotrienol and β-tocotrienol. Pyrophosphate compounds from reactions early in all three sets are provided as products from terpenoid backbone biosynthesis. Meanwhile, chorismate, which also begins in the cytoplasm, can follow two distinct pathways. The first involves its transfer into the mitochondrion, where it undergoes a series of reactions until it forms ubiquinone. This ubiquinone can be used for oxidative phosphorylation within the mitochondrion. The second pathway chorismate follows brings it into the chloroplast, where multiple PHYLLO enzymes catalyze a series of reactions to form 2-succinyl benzoate. With the addition of coenzyme A, 2-succinyl benzoyl-CoA can be moved out of the chloroplast and into the peroxisome. Through a pair of reactions, this compound is ultimately hydrolyzed to form 1,4-dihydroxy-2-naphthoate, which is transported back into the chloroplast to form phylloquinol. Phylloquinone can also react with a hydrogen ion to form phylloquinol in the cell membrane.

Metabolic

SMP0122616

Pw123931 View Pathway
Metabolite

Starch and Sucrose Metabolism

Drosophila melanogaster
Starch is the main polysaccharide storage form in plants, composed of glucose units in the form of amylose and amylopectin. Sucrose is a disaccharide sugar composed of fructose and glucose units. In Drosophilia melanogaster, starch and sucrose are metabolised into monosaccharide units which are used as energy by the organism. Starch is metabolised to maltose and dextrin by alpha amylase enzyme. Maltose and dextrin are then metabolised to D-glucose units. Starch can also be metabolised to glucose-1-phosphate which goes through a series of reactions to form D-glucose. Starch is metabolised into glucose-1-phosphate by the enzymes glycogen phosphorylase and glycogen branching enzyme. Glucose-1-phosphate can form D-glucose in 2 ways. It is either converted to glucose-6-phosphate by phosphoglucomuctase-1 which goes on to form D-glucose through D-glucose-6-phosphate phosphohydrolase; or it forms UDP-glucose by UDP-glucose pyrophosphorylase. UDP-glucose is a compound which is linked to the amino acid and nucleotide sugar metabolism pathway. Trehalose-6-phosphate synthase then forms trehalose-6-phosphate from UDP-glucose. Trehalose-6-phosphate is metabolised to trehalose by trehalose phosphatase. Finally, D-glucose is formed from trehalose via the enzyme trehalase. Sucrose is also metabolised to D-glucose units. First, sucrose is converted into D-fructose by alpha-glucosidase, D-fructose then forms fructose-6-phosphate through hexokinase-1. Fructose-6-phosphate forms glucose-6-phosphate via glucose-6-phosphate isomerase. Glucose-6-phosphate forms D-glucose in 2 ways; either directly through the D-glucose-6-phosphate phosphohydrolase enzyme which converts glucose-6-phosphate into D-glucose, or via phosphoglucomuctase-1 which forms glucose-1-phosphate which then goes on to form D-glucose as previously mentioned.

Metabolic

SMP0122628

Pw123943 View Pathway
Metabolite

Fructose and Mannose Metabolism

Drosophila melanogaster
Fructose and mannose are monosaccharides that can be found in a variety of foods, though they are both metabolized and treated differently by the body. For mannose, it begins with the D-form D-mannose which is widely distributed in mannans and hemicelluloses. D-Mannose (which can be found in the mitochondria or outside cells) is first taken up into the intracellular space by a phosphotransferase system (hexokinase) and converted into mannose-6-phosphate. This can then take one of two pathways. In the first it is subsequently converted by mannose-6-phosphate isomerase into β-D-fructose 6-phosphate, an intermediate of glycolysis. The β-D-fructose 6-phosphate is further phosphorylated by fructose-1,6-bisphosphatase to β-D-fructose 1,6-bisphosphate, which can also be converted back via ATP dependent 6-phosphofructokinase. The β-D-fructose 1,6-bisphosphate is then split into two compounds: dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate, which either continues through glycolysis, or gets catalyzed by triosephosphate isomerase into dihydroxyacetone phosphate in a reversible reaction. The second pathway for mannose-6-phosphate begins with its conversion into D-mannose 1-phosphate by phosphomannomutase 1. D-Mannose 1-phosphate is then converted into diphosphoric acid and guanosine diphosphate mannose (GDP mannose), which is a substrate for dolichol-linked oligosaccharide synthesis. GDP mannose can either continue on into N-glycan biosynthesis, or be converted to GDP-L-fucose via 3 enzymatic reactions carried out by two proteins: GDP-mannose 4,6-dehydratase (which produces the intermediate GDP-4-dehydro-6-deoxy-D-mannose) and GDP-L-fucose synthase, which converts the intermediate into GDP-L-fucose. The metabolism of mannose is interlinked with the metabolism of fructose, which begins with D-fructose also within the mitochondria. Metabolism of fructose is linked up with metabolism of mannose via fructolysis wherein ketohexokinase initially produces D-fructose 1-phosphate, (found in the cytosol). This is then split by fructose bisphosphate aldolase into D-glyceraldehyde and dihydroxyacetone phosphate, linking it to the mannose metabolic pathway. Alternatively, D-fructose can also be converted into β-D-fructose 6-phosphate by hexokinase as it is imported into the cytosol of the cell. β-D-Fructose 6-phosphate then enters the previously outlined pathway shared between fructose and mannose. D-Fructose can also be reversibly converted to sorbitol by a sorbitol dehydrogenase (LD47736p), which is subsequently reversibly converted to α-D-glucose used in the galactose metabolic pathway via an aldose reductase (CG6084, isoform D). Alternatively, D-fructose could also instead go on to take part in the amino sugar and nucleotide sugar metabolic pathway.

Metabolic

SMP0122610

Pw123924 View Pathway
Metabolite

Taurine & Hypotaurine Metabolism

Drosophila melanogaster
Taurine and hypotaurine are aminosulfinic acids. Taurine has many physiological functions as neuromodulators, membrane stabilizers, facilitator of ion transport and aiding auditory transduction. Hypotaurine has roles such as antioxidant and a protective agent. Taurine and hypotaurine are synthesized from L-cysteine. L-Cysteine is involved in cyanoacid metabolism and glutathione metabolism. L-Cysteine goes through redox reactions, elimination reactions and other metabolism pathways to eventually form taurine and hypotaurine. L-Cysteine is converted to cysteamine, which can then form hypotaurine through the enzyme cysteamine dioxygenase. L-Cysteine can also be converted to 3-sulfinoalanine through the enzyme cysteine dioxygenase. Hypotaurine can then be formed from the enzymes glutamate decarboxylase and sulfinoalanine decarboxylase acting on 3-sulfinoalanine. 3-sulfinoalanine can form taurine by first converting to L-cysteate. L-Cysteate is then metabolized to taurine via glutamate decarboxylase and sulfinoalanine decarboxylase. The hypotaurine formed in this pathway can be metabolised to taurine, then taurine is metabolised to 5-L-glutamyl-taurine by reacting with (5-L-glutamyl)-peptide via the enzyme gamma-glutamyltranspeptidase. Taurine can also undergo excretion from the organism.

Metabolic

SMP0122634

Pw123949 View Pathway
Metabolite

Pyrimidine Metabolism

Arabidopsis thaliana
Pyrimidines are heterocyclic aromatic organic compounds. These nitrogenous bases form an essential part of nucleic acids in DNA and RNA. Cytosine and thymine are inserted into the structure of DNA, while RNA utilizes cytosine and uracil. In metabolism, the pyrimidine is usually cleaved and the end products are typically beta-amino acids, ammonia and carbon dioxide. Pyrimidine metabolism in Arabidopsis thaliana occurs mostly in the nucleus, cytosol and chloroplast of the cell, with a few reactions taking place in the mitochondria, ER, vacuole, plasma membrane and peroxisome. The pyrimidines are incorporated into DNA in the compounds dTTP and dCTP. The apyrase enzyme or nucleoside diphosphate kinase-1 can convert dTTP to dTDP. Apyrase or thymidylate kinase can then convert dTDP to dTMP. Nucleotide diphosphatase can also metabolize dTTP directly to dTMP. The enzyme 5’-nucleotidase converts dTMP to thymidine. An unknown enzyme then metabolizes thymidine to thymine. Thymine is converted into dihydrothymine by dihydropyrimidine dehydrogenase. Dihydropyrimidinase converts dihydrothymine to 3-ureidoisobutyrate, which then forms 3-aminoisobutyrate via beta-ureidopropionase. Nucleotide diphosphate kinase-1 converts dCTP into dCDP, which produces dCMP via the enzyme UMP-CMP kinase-1. Two unknown enzymes metabolize dCMP to 2'-deoxy-5-hydroxymethylcytidine-5'-diphosphate which is then converted to 2'-deoxy-5-hydroxymethylcytidine-5’-triphosphate by nucleotide diphosphate kinase-1. Deoxycytidine is formed from dCMP by 5’-nucleotidase and is converted to deoxyuridine via cytidine deaminase. Thymidine kinase converts deoxyuridine to dUMP. The compound dUMP can also be formed from dCMP using dCMP deaminase. The dUMP formed is converted into dTMP by bifunctional dihydrofolate reductase-thymidylate synthase-1. The dTMP follows the metabolism pathway as previously mentioned to eventually form 3-aminoisobutyrate. The pyrimidines are incorporated into RNA in the compounds UTP and CTP. UTP is metabolised to UDP using the enzyme apyrase or nucleoside disphosphate kinase-1. UDP then forms UMP via apyrase or via the enzymes UMP-CMP kinase-1 and uridylate kinase. UMP can be directly formed from UTP using nucleotide diphosphatase. Uridine is produced from metabolism of UMP by the enzyme 5’-nucleotidase. Uridine nucleosidase-1 then forms uracil from uridine. Uracil phosphoribosyltransferase can also create uracil directly from UMP. Dihydrouracil is made from uracil via dihydropyrimidine dehydrogenase. Dihydropyrimidinase converts dihydrouracil to 3-ureidopropionate. Finally, β-alanine is generated from 3-ureidopropionate through the enzyme Beta-ureidopropionase. UTP can be converted into CTP via CTP synthase. CTP is then converted into CDP via apyrase or nucleoside disphosphate kinase-1. CDP forms dCDP via ribonucleoside-diphosphate reductase. The dCDP follows the metabolism pathway as previously mentioned, forming 3-aminoisobutyrate. CDP can also form CMP via apyrase or UMP-CMP kinase-1. CMP can be directly produced from CTP using nucleotide diphosphatase. Cytidine is then generated from the metabolism of CMP by 5’-nucleotidase. The cytidine formed can then be metabolized into uracil via cytidine deaminase. Uridine then follows the same metabolism pathway as previously mentioned to eventually form β-alanine.

Metabolic

SMP0122611

Pw123925 View Pathway
Metabolite

Synthesis and Degradation of Ketone Bodies

Drosophila melanogaster
Ketone bodies are water-soluble compounds that are produced when fatty acids are broken down during metabolism as by-products. They can be used as a source of energy in the heart and the brain and serve as an important energy source during fasting. The use of ketone bodies in the body has two key parts: ketogenesis and ketolysis, both which occur within the mitochondrial matrix. The former is mediated primarily by 2 key enzymes. 3-hydroxy-3-methaglutaryl coenzyme A synthase is involved in the final major regulatory reaction in the process and condenses acetyl CoA to form 3-hydroxy-3-methylglutaryl-CoA. 3-hydroxymethyl-3-methaglutaryl-CoA lyase on the other hand catalyzes the formation of acetoacetic acid from (3S)-hydroxy-3-methylglutaryl-CoA. Ketolysis however, involves two reversible reactions that mediate activation of free acetoacetic acid from acetoacetyl-CoA and creation of acetyl-CoA to be used as energy by the body. The acetoacetate is activated to the acetoacetyl-CoA by the enzyme succinyl-CoA: 3-ketoacid-coenzyme A transferase. Acetyl CoA acetyltransferase (LD24105p) equilibrates the mitochondrial pools of acetoacetyl-CoA and acetyl-CoA. This role means that LD24105p is involved in both ketogenesis and ketolysis. Acetoacetic acid can alternatively be catalyzed by short-chain dehydrogenase/reductase to form (R)-3-hydroxybutyric acid along with NADH.

Metabolic

SMP0122622

Pw123937 View Pathway
Metabolite

Carbon Fixation in Photosynthetic Organisms

Arabidopsis thaliana
Carbon fixation is the process where inorganic carbon, usually in the form of carbon dioxide, is converted into organic molecules. The carbon fixation pathway in Arabidopsis thaliana consists of 3 cycles: Reductive pentose phosphate cycle (Calvin-Benson cycle), C4-dicarboxylic acid cycle and crassulacean acid metabolism. The Calvin-Benson cycle involves the light-independent reaction of photosynthesis and takes place through three general steps (carbon fixation, reduction and regeneration). Plants which live in unfavorable conditions like hot and dry climates have adapted to fix carbon dioxide through alternative cycles before it can move into the Calvin-Benson cycle. The C4-dicarboxylic acid cycle and the crassulacean acid metabolism (CAM) cycle are these alternative pathways. The C4-dicarboxylic acid cycle efficiently fixes carbon dioxide at low concentrations so the plants do not have to open their stomata too often. Plants with the CAM cycle open their stomata to fix CO2 only at night and stores it in an organic form. During the day, when the stomata is closed, the carbon dioxide is removed from the stored organic form and enters the Calvin-Benson cycle. In the Calvin-Benson cycle, carbon fixation occurs when ribulose bisphosphate carboxylase converts ribulose-1,5-bisphosphate, carbon dioxide and water into glycerate-3-phosphate. Ribulose-1,5-bisphophate is also linked to the glyoxylate and dicarboxylate metabolism pathway which is involved in forming glycerate-3-phosphate. The reduction step involves phosphoglycerate kinase-2 converting glycerate-3-phosphate into 1,3-bisphosphoglycerate, using ATP. Glyceraldehyde-3-phosphate dehydrogenase then converts 1,3-bisphosphoglycerate into glyceraldehyde-3-phosphate, using NADPH. Some glyceraldehyde-3-phosphate may go into the cytoplasm to form compounds used by the plant. The regeneration step includes reforming the ribulose-1,5-bisphosphate so more carbon fixation can occur. Glyceraldehyde-3-phosphate is converted into fructose-1,6-bisphosphate using fructose bisphosphate aldolase. Fructose 1,6-bisphosphatase then converts fructose-1,6-bisphosphate into fructose-6-phosphate. Fructose-6-phosphate along with glyceraldehyde-3-phosphate can then form erythrose-4-phosphate and xyulose-5-phoshphate through transketolase-2. Glyceraldehyde-3-phosphate can also form glycerone phosphate (linked to the gluconeogenesis cycle which is connected to starch formation) through triosephosphate isomerase. Glycerone phosphate and erythrose-4-phosphate together forms sedoheptulose 1,7-bisphosphate through fructose-bisphosphate aldolase. Sedoheptulose 1,7-bisphosphatase creates sedoheptulose 7-phosphate from sedoheptulose 1,7-bisphosphate. Sedoheptulose 7-phosphate and glyceraldehyde-3-phosphate forms ribose-5-phoshphate and xyulose-5-phosphate. Ribose-5-phosphate and xyulose-5-phosphate can from ribulose-5-phosphate using ribose-5-phosphate isomerase and ribulose phosphate-3 epimerase respectively. Finally, ribulose-1,5-bisphosphate is regenerated from ribulose-5-phosphate using phosphoribulokinase. The C4-dicarboxylic acid pathway fixes carbon dioxide through phosphoenolpyruvate carboxylase-1, which converts phosphoenolpyruvate into oxaloacetate. Oxaloacetate forms malate with chloroplastic malate dehydrogenase. Oxaloacetate can also form aspartate through aspartate aminotransferase, and aspartate forms oxaloacetate through that same enzyme. The oxaloacetate can produce malate through cytoplasmic malate dehydrogenase. The oxaloacetate can regenerate phosphoenolpyruvate and carbon dioxide (which enters the Calvin-Benson cycle) through phosphoenolpyruvate carboxykinase. The malate formed is stored in the bundle-sheath cells and can be broken down to release carbon dioxide which enters the Calvin-Benson cycle. This occurs through mitochondrial NAD-dependent malic enzyme-1 and chloroplastic NADP-dependent malic enzyme-4 which form pyruvate and carbon dioxide. The pyruvate formed in the mitochondria goes on to form alanine through alanine aminotransferase and alanine forms pyruvate through that same enzyme which goes into the chloroplast. Pyruvate in the chloroplast then regenerates phosphoenolpyruvate through pyruvate, phosphate dikinase-1. The CAM cycle fixes carbon dioxide in the atmosphere using phosphoenolpyruvate carboxylase-1 to convert phosphoenolpyruvate into oxaloacetate. Oxaloacetate then uses malate dehydrogenase to form malate which is stored in cell vacuoles. In the day, when the stomata are closed, malate is broken down into pyruvate through NADP-dependent malic enzyme-4. This process releases the carbon dioxide which enters the Calvin-Benson cycle. Pyruvate then reforms the phosphoenolpyruvate by pyruvate, phosphate dikanse-1. The phosphoenolpyruvate is linked to the glycolysis/gluconeogenesis pathway which is involved in forming starch.

Metabolic
Showing 110281 - 110290 of 110297 pathways