Pathway maps

Glycolysis and gluconeogenesis (short map)
Glycolysis and gluconeogenesis (short map)

Object List (links open in MetaCore):

2.7.1.40, 2.7.1.11, 3-Phospho-(D)- glyceroyl-phosphate, ALDOA Homotetramer, (D)-Glyceraldehyde 3-phosphate, PGAM3, 4.2.1.11, PGK2 Monomer, G6PT, MDH2 Homodimer, PGK1 Monomer, Dihydroxyacetone phosphate, PGAM2 Homodimer, G6PT1, Dimer of identical or nonidentical chains of three types, GLUT4, HXK4, PFKM Tetramer, G6PI Homodimer, 4.1.1.32, D-glucose, PPCKM, ENO2, TPI1 Homodimer, F16P Homotetramer, Alpha-D-glucose -6-phosphate, 4.1.2.13, 6.4.1.1, KPYR Homotetramer, 1.1.1.37, 2.7.1.1, HXK1 Monomer, 5.3.1.9, 3.1.3.11, 2-oxosuccinate, Pyruvate, (S)-Malic acid, (S)-Malic acid, 1.2.1.12, 2.7.2.3, 2-Oxo-succinic acid, PMGE Homodimer, G3PT Homotetramer, F16Q, G3P1 Homotetramer, 2-Phospho- (D)-glyceric acid, 3.1.3.9, ALDOC Homotetramer, HXK2 Monomer, PFKP Tetramer, Pyruvic acid, PKM2 Homotetramer, 1.1.1.37, Beta-D-fructose-1,6-bisphosphate, 5.3.1.1, PYC, 5.4.2.1, ENO3, PGAM1 Homodimer, D-Glycerate 3-phosphate, Phosphoenol pyruvate, HXK3 Monomer, PFKL Tetramer, G3P2 Homotetramer, PPCKC, transport, Beta-D-fructose -6-phosphate, Glucose, ALDOB Homotetramer, MDH1 Homodimer, ENO1

Description

Glycolysis and gluconeogenesis (short map)

D-Glucose is the major energy source for mammalian cells as well as an important substrate for protein and lipid synthesis. Mammalian cells take up D-Glucose from extracellular fluid into the cell through two families of structurally related glucose transporters. Solute carrier family 2 (facilitated glucose transporter), member 4 ( GLUT4 ) is one such transporters. It mediates bidirectional and energy-independent process of glucose transport in most tissues and cells [1], [2].

The first step of D-Glucose conversion is its immediate phosphorylation to alpha - D-Glucose-6-phosphate by the family of hexokinases: Hexokinase 1 ( HXK1) [3], [4], [5], Hexokinase 2 (HXK2) [6], [3], Hexokinase 3 ( HXK3) [7], [3], and Glucokinase (hexokinase 4) HXK4 [8], [3]. The reverse reaction takes place in gluconeogenesis and plays a crucial role in maintaining D-Glucose homeostasis. Solute carrier family 37 (glucose-6-phosphate transporter), member 4 ( G6PT1 ) translocates alpha - D-Glucose-6-phosphate from the cytoplasm into the lumen of the endoplasmic reticulum [9], [10] where Glucose-6-phosphatase, catalytic subunit ( G6PT ) hydrolyses the alpha - D-Glucose-6-phosphate into D-Glucose and phosphate [11], [10].

Alpha - D-Glucose-6-phosphate is further converted to Beta-D-Fructose 6-phosphate by Glucose phosphate isomerase ( GPI ) [12], [13], [14]. Then, phosphofructokinases (Phosphofructokinase, muscle - PFKM, Phosphofructokinase, platelet - PFKP, Phosphofructokinase, liver - PFKL ) attach the second phosphate group to Beta-D-Fructose 6-phosphate resulting in formation of Beta-D-Fructose 1,6-bisphosphate [15], [16], [17]. Beta-D-Fructose 1,6-bisphosphate is further hydrolyzed by important gluconeogenic enzymes Fructose-1,6-bisphosphatase 1 ( F16P) and Fructose-1,6-bisphosphatase 2 ( F16Q ) to Beta-D-Fructose 6-phosphate and phosphate [18], [19].

Vertebrate aldolases exist as three isozymes with different tissue distributions and kinetics: Aldolase A, fructose-bisphosphate ( ALDOA ) (muscle and red blood cell), Aldolase B, fructose-bisphosphate ( ALDOB ) (liver, kidney, and small intestine), and Aldolase C fructose-bisphosphate ( ALDOC ) (brain and neuronal tissue). These are ubiquitous enzymes that catalyze the reversible aldol cleavage of Beta-D-Fructose 1,6-bisphosphate (and also D-Fructose-1-phosphate ) to Dihydroxyacetone phosphate and either (D)-Glyceraldehyde 3-phosphate or Glyceraldehyde, respectively [20], [21], [22]. Dihydroxyacetone phosphate is further reversibly isomerized to (D)-Glyceraldehyde 3-phosphate by Triosephosphate isomerase 1 ( TPI1 ) [23], [24].

(D)-Glyceraldehyde 3-phosphate is metabolized to 3-Phospho-(D)-glyceroyl phosphate by glyceraldehyde-3-phosphate dehydrogenases ( G3P1, G3P2, G3PT ) [25], [26], [27]. Enzymes Phosphoglycerate kinase 1 ( PGK1 ), Phosphoglycerate kinase 2 ( PGK2 ) catalyze the reversible transfer of a phosphoryl group from 3-Phospho-(D)-glyceroyl phosphate to ADP which results in formation of D-Glycerate 3-phosphate [28], [29], [30]. D-Glycerate 3-phosphate is enzymatically converted into 2-Phospho-(D)-glyceric acid by phosphoglycerate mutase that has several isoforms: Phosphoglycerate mutase 1 (brain) - PGAM1, Phosphoglycerate mutase 2 (muscle) - PGAM2, Phosphoglycerate mutase family 3 - PGAM3, and by a multifunctional enzyme 2,3-Bisphosphoglycerate mutase ( PMGE ) [31], [32], [33], [34], [35]. After releasing water, catalyzed by Enolase 1, (alpha), ( ENO1 ), Enolase 3 (beta, muscle) (ENO3), Enolase 2 (gamma, neuronal) ( ENO2 ) Phosphoenolpyruvate is formed [36], [37], [38]. Then it is converted to Pyruvic acid by Pyruvate kinase, liver and RBC ( KPYR ) [39], [40] and Pyruvate kinase, muscle ( PKM2 ) [41], [42].

Pyruvate carboxylase ( PYC ) converts Pyruvic acid to 2-Oxo-succinic acid [43], [44] that is reversibly reduced by Malate dehydrogenase 1, NAD (soluble) ( MDH1 ) and Malate dehydrogenase 2, NAD (mitochondrial) ( MDH2 ) to (S)-Malic acid [45], [46], [47], [48] and is metabolized back to Phosphoenolpyruvate by Phosphoenolpyruvate carboxykinase 2 (mitochondrial) ( PPCKM ) [49], [50] and Phosphoenolpyruvate carboxykinase 1 (soluble) ( PPCKC ) [51], [52].

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