Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Glycolysis and gluconeogenesis (short map)


Log In to Post A Comment

Glycolysis and gluconeogenesis (short map)

Glycolysis and gluconeogenesis (short map)

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

The first step of D-Glucose conversion is its immediate phosphorylation toalpha - D-Glucose-6-phosphate by the family of hexokinases: Hexokinase 1 (HXK1) [3], [4], Hexokinase 2(HXK2) [5], [6], Hexokinase 3 ( HXK3) [7], [6], and Glucokinase (hexokinase 4) HXK4 [8],[6]. The reverse reaction takes place in gluconeogenesis and plays a crucialrole 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 endoplasmicreticulum [9], [10] where Glucose-6-phosphatase, catalyticsubunit ( G6PT ) hydrolyses the alpha - D-Glucose-6-phosphate intoD-Glucose and phosphate [11], [10].

Alpha - D-Glucose-6-phosphate is further converted to Beta-D-Fructose6-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-phosphateresulting in formation of Beta-D-Fructose 1,6-bisphosphate [15], [16], [17]. Beta-D-Fructose 1,6-bisphosphate is furtherhydrolyzed by important gluconeogenic enzymes Fructose-1,6-bisphosphatase 1 (F16P) and Fructose-1,6-bisphosphatase 2 ( F16Q ) to Beta-D-Fructose6-phosphate and phosphate [18], [19].

Vertebrate aldolases exist as three isozymes with different tissue distributions andkinetics: 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). Theseare ubiquitous enzymes that catalyze the reversible aldol cleavage of Beta-D-Fructose1,6-bisphosphate (and also D-Fructose-1-phosphate ) to Dihydroxyacetonephosphate and either (D)-Glyceraldehyde 3-phosphate or Glyceraldehyde,respectively [20], [21], [22]. Dihydroxyacetonephosphate is further reversibly isomerized to (D)-Glyceraldehyde 3-phosphateby Triosephosphate isomerase 1 ( TPI1 ) [23], [24].

(D)-Glyceraldehyde 3-phosphate is metabolized to 3-Phospho-(D)-glyceroylphosphate by glyceraldehyde-3-phosphate dehydrogenases ( G3P1, G3P2, G3PT )[25], [26], [27]. Enzymes Phosphoglycerate kinase 1 (PGK1 ), Phosphoglycerate kinase 2 ( PGK2 ) catalyze the reversible transferof a phosphoryl group from 3-Phospho-(D)-glyceroyl phosphate to ADP whichresults in formation of D-Glycerate 3-phosphate [28], [29],[30]. D-Glycerate 3-phosphate is enzymatically converted into2-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 multifunctionalenzyme 2,3-Bisphosphoglycerate mutase ( PMGE ) [31], [32],[33], [34], [35]. After releasing water, catalyzed byEnolase 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 Pyruvatekinase, liver and RBC ( KPYR ) [39], [40] and Pyruvatekinase, muscle ( PKM2 ) [41], [42].

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