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Glycolysis
Uni of Notts, Signalling & Metabolic Regulation, Year 2, Topic 7
| Term | Definition |
|---|---|
| Historical discovery leading to glycolysis understanding | 19th century cell-free fermentation used lysed yeast showed metabolism could occur outside cells, leading to discovery of glycolytic enzymes and pathway after WW1 |
| Hexokinase reaction | Phosphorylates glucose at C6 to form glucose-6-phosphate (G6P), trapping glucose inside the cell. G6P can then inhibit the enzyme non-competitively, decreasing Vmax |
| How glucokinase differs from hexokinase | 50x lower affinity for glucose, not inhibited by G6P, active at high glucose, supports biosynthetic storage pathways in liver |
| How the first ATP of glycolysis is generated | Pyruvate kinase transfers phosphoryl from phosphoenolpyruvate (PEP) to ADP to form ATP & pyruvate |
| Pyruvate kinase isoforms *Examples, don't need to memorise* | PKM1 (heart/muscle/brain) supports catabolism & energy production; PKM2 supports growth (embryos/cancer); PKL in liver supports anabolism |
| How pyruvate kinase is regulated | Downregulated by ATP, citrate, H+ (switches off during acidosis), & alanine, upregulated by fructose-1,6-bisphosphate & AMP |
| Structure of pyruvate kinase | Tetramer with identical subunits; each monomer has some independent activity & can bind F1,6-BP |
| Role of phosphofructokinase-1 | Phosphorylates F6-P to F1,6-BP. Rate limiting step of glycolysis & most important control point in mammalian glycolysis |
| How the second ATP of glycolysis is generated & the implications of this | Adenylate kinase converts 2ADP ↔ ATP + AMP, increasing AMP which activates PFK-1. Also downregulated during acidosis) |
| Role of F2,6-BP | Only found in liver cells, very potent PFK-1 allosteric activator. Binds switching it from T (inactive) to L (active) conformations to promote glycolysis |
| PFK-2/FBPase-2 | Enzyme containing both a kinase & phosphatase domain to catalyse either the formation of F2,6-BP or hydrolysis of it to regulate PFK1 |
| How glucagon regulates PFK-2/FBPase-2 | Upregulates adenylyl cyclase, cAMP disinhibits PKA, PKA phosphorylates the single serine residue on PFK-2, activates the phosphatase domain, FBPase-2 hydrolyses F2,6-BP, glycolysis inhibited |
| phosphogluceryl-lysine (pgK) | Non-enzymatic PTM of lysine residues where a molecule of 1,3-bisphosphate glycerate (1,3-BPG) formed as a glycolytic intermediate binds covalently to the lysine R-group. Happens in high glucose |
| How 1,3-BPG regulates glycolytic enzymes | Accumulation from too much glycolysis forms pgK with lysine residues around active sites decreasing activity & steadily changing biosynthetic pathways by allowing intermediate accumulation |
| How glycolysis can be exploited to screen for non-brain tumours | Radiolabelled non-metabolically active analogues accumulate in tissues with unnaturally high glycolysis, indicating tumours. Doesn't work on brain because it has much higher glucose |
| How fructose & galactose are glycolytically regulated | Fructose enters glycolysis as F6P, galactose enters as G1P then G6P. Since they bypass regulatory steps, they alter glycolytic control. Part of why the cell favours glucose |
Created by:
Denny12
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