241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Glycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabolites: six-carbon compounds of glucose-6P and fructose-6P and three-carbon compounds of glycerone-P, glyceraldehyde-3P, glycerate-3P, phosphoenolpyruvate, and pyruvate [MD:M00001]. Acetyl-CoA, another important precursor metabolite, is produced by oxidative decarboxylation of pyruvate [MD:M00307]. When the enzyme genes of this pathway are examined in completely sequenced genomes, the reaction steps of three-carbon compounds from glycerone-P to pyruvate form a conserved core module [MD:M00002], which is found in almost all organisms and which sometimes contains operon structures in bacterial genomes. Gluconeogenesis is a synthesis pathway of glucose from noncarbohydrate precursors. It is essentially a reversal of glycolysis with minor variations of alternative paths [MD:M00003].
Serine is derived from 3-phospho-D-glycerate, an intermediate of glycolysis [MD:M00020], and glycine is derived from serine. Threonine is an essential amino acid, which animals cannot synthesize. In bacteria and plants, threonine is derived from aspartate [MD:M00018].
Carbon metabolism is the most basic aspect of life. This map presents an overall view of central carbon metabolism, where the number of carbons is shown for each compound denoted by a circle, excluding a cofactor (CoA, CoM, THF, or THMPT) that is replaced by an asterisk. The map contains carbon utilization pathways of glycolysis (map00010), pentose phosphate pathway (map00030), and citrate cycle (map00020), and six known carbon fixation pathways (map00710 and map00720) as well as some pathways of methane metabolism (map00680). The six carbon fixation pathways are: (1) reductive pentose phosphate cycle (Calvin cycle) in plants and cyanobacteria that perform oxygenic photosynthesis, (2) reductive citrate cycle in photosynthetic green sulfur bacteria and some chemolithoautotrophs, (3) 3-hydroxypropionate bi-cycle in photosynthetic green nonsulfur bacteria, two variants of 4-hydroxybutyrate pathways in Crenarchaeota called (4) hydroxypropionate-hydroxybutyrate cycle and (5) dicarboxylate-hydroxybutyrate cycle, and (6) reductive acetyl-CoA pathway in methanogenic bacteria.
This map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module for conversion of three-carbon compounds from glyceraldehyde-3P to pyruvate [MD:M00002], together with the pathways around serine and glycine. This KEGG module is the most conserved one in the KEGG MODULE database and is found in almost all the completely sequenced genomes. The extensions are the pathways containing the reaction modules RM001, RM033, RM032, and RM002 for biosynthesis of branched-chain amino acids (left) and basic amino acids (bottom), and the pathways for biosynthesis of histidine and aromatic amino acids (top right). It is interesting to note that the so-called essential amino acids that cannot be synthesized in human and other organisms generally appear in these extensions. Furthermore, the bottom extension of basic amino acids appears to be most divergent containing multiple pathways for lysine biosynthesis and multiple gene sets for arginine biosynthesis.
Glucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Glucagon also stimulates hepatic mitochondrial beta-oxidation to supply energy for glucose production. Glucagon performs its main effect via activation of adenylate cyclase. The adenylate-cyclase-derived cAMP activates protein kinase A (PKA), which then phosphorylates downstream targets, such as cAMP response element binding protein (CREB) and the bifunctional enzyme 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase (one of the isoforms being PFK/FBPase 1, encoded by PFKFB1).
Malignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. He showed that cancer cells consume a large amount of glucose, maintain high rate of glycolysis and convert a majority of glucose into lactic acid even under normal oxygen concentrations (Warburg's Effects). More recently, it has been recognized that the 'Warburg effect' encompasses a similarly increased utilization of glutamine. From the intermediate molecules provided by enhanced glycolysis and glutaminolysis, cancer cells synthesize most of the macromolecules required for the duplication of their biomass and genome. These cancer-specific alterations represent a major consequence of genetic mutations and the ensuing changes of signalling pathways in cancer cells. Three transcription factors, c-MYC, HIF-1 and p53, are key regulators and coordinate regulation of cancer metabolism in different ways, and many other oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53.
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