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WEEK 9:
Carbohydrates 1- glucose uptake and storage:
| Question | Answer |
|---|---|
| what are metabolic pathways | series of branches and interconnected enzymatic reactions producing specific products, using metabolites (substrates/ intermediates and products) |
| where do metabolic pathways take place | reactions can be compartmentalised (in eukaryotes) with transport systems moving metabolites between organelles and acting as control points |
| catabolic | break down |
| anabolic | make |
| range of blood glucose | 4-8mM |
| enantiomers of glucose | D and L |
| form of glucose in solution | is in equilibrium with 6 membered ring form (glucopyranose) in solution |
| anomers of glucose | as C1 is asymmetric, there are alpha and beta anomers of glucose |
| furanoses | 5 membered rings of glucose |
| glucopyranose | 6 membered rings of glucose |
| summarised digestion of carbohydrates (polysaccharides) | mouth polysaccharides (salivary amylase) -> oligosaccharides (3-10) -> pancreatic enzymes (amylase) + SI) -> final digestion on mucosal cells -> glucose cotransported into cells with Na+ |
| final digestion of carbohydrates occurs where | on mucosal cells |
| ATP dependent Na+ cotransporter of glucose | found in intestinal epithelial cells working against concentration gradient where glucose is coupled to sodium transport (cotransport) |
| Na+ independent (passive) transport of glucose | glucose moves down concentration gradient and is expressed throughout body |
| where are glucose Na+ transporters found | in intestinal epithelial cells |
| store of glucose in liver and muscles is | glycogen |
| disruption of glycogen metabolism can cause what | glycogen storage disease (GSDs) |
| role of glycogen in muscle | main fuel reserve for ATP synthesis |
| amount of glycogen in muscle | 400g (1-2% fresh weight) |
| role of glycogen in liver | mobilisation of glycogen helps maintain blood glucose levels around 5mM |
| amount of glycogen in liver | 100g (10% fresh weight) |
| glycogen structure | branched polysaccharide connected by a(1-4) glycosidic bonds in chains and a(1-6) glycosidic bonds at branch points with each glycogen molecule having a single origin linked to a protein (glycogenin acts a primer to add molecules together) |
| glucose 1 phosphate (G1P) | initial substrate for synthesis and main product from breakdown, formed from glucose-6-phosphase by phosphoglucomutase |
| a(1-6) glycosidic bonds | branch |
| a(1-4) glycosidic bonds | chain points |
| enzymes that synthesise and break down glycogen require | minimum of 4 glucose residues to bind (limit dextrin) |
| starting point of glycogenesis involves | glycogenin enzyme acting as a primer to form initial 8 glucose chain using UDP-glucose (formed from glucose 1-P and UTP) i |
| UDP-glucose formed from | glucose 1-P and UTP |
| extension of glycogen involves | chain extended by glycogen synthase using UDP-glucose to form a(1-4) bonds and branches are added by a transferase (breaking chain and reattaching it upstream) as a(1,6) bond |
| starting point of glycogenolysis | glycogen molecule has multiple ends |
| glycogen phosphorylase role in glycogenolysis | cleaves a(1,4) bond of terminal glucose form glycogen and adds Pi to release glucose 1-phosphate and continues this process until 4 glucose units remain on the glycogen branch |
| equation for glycogenolysis | (glucose)n + Pi -> (glucose)n-1 + glucose 1-P |
| what happens during glycogenolysis to remove branches | a single enzyme with 2 active sites carry out 2 reactions (transferase reaction and glycosidase reaction) |
| transferase action of single enzyme in glycogenolysis | three of the four glucose units on branch are moved to end of main chain |
| glycosidase action of single enzyme in glycogenolysis | hydrolytically removes single remaining sugar with a(1,6) glycosidase activity after transferase has moved the other 3 off the branch to the main chain |
| liver during well fed state | increases synthesis |
| liver during fasting state | increases breakdown |
| muscle during rest periods | increases synthesis |
| muscle during exercise | increases breakdown |
| 2 levels of regulation | hormonal regulation (of glycogen synthase and phosphorylase via phosphorylation/ dephosphorylation) with are allosterically regulated (hormonal and allosterically) |
| examples of glucogenic hormones | adrenaline and glucagon |
| how do glucogenic hormones act | through second messenger - cAMP to increase glucose levels |
| adrenaline acts on | both liver and muscle |
| glucagon only acts on | liver alone |
| how to inactivate glycogen synthase | adrenaline and glucagon activate PKA via cAMP which inactivates synthase |
| how to activate glycogen synthase | insulin activates PP1 and inactivates PKA which activates synthase |
| allosteric activators | glucose 6-P and ATP |
| dephosphorylated glycogen phosphate means its | active |
| phosphorylated glycogen phosphate means its | inactive |
| what happens when glycogen synthase (active) gets phosphorylated via PKA | becomes inactive |
| what happens when glycogen synthase (inactive) gets dephosphorylased by protein phosphatase 1 | becomes active |
| phosphorylation of glycogen synthase at multiple sites leads to | strong inactivation |
| allosteric activators | AMP (in muscle only) |
| how to activate phosphorylase | adrenaline and glucagon activate PKA via cAMP activating phosphorylase |
| how to inactivate phosphorylase | insulin activates PP1 and inactivates PKA inactivating phosphorylase |
| allosteric regulation | permits faster response (ms v sec/min) and can override hormone mediated covalent regulation (eg exercise just after eating) |
| effects of high energy | G6P and ATP inhibit glycogen phosphorylase and G6P activates glycogen synthesis (make more glycogen) |
| effects of low energy | AMP activates muscle glycogen phosphorylase which leads to breakdown of glycogen |
| in muscle, glycogen breakdown is activated by | calcium |
| calcium binds and activates what | calcium binds to and activates the calmodulin subunit of glycogen phosphorylase kinase b (inactive form) which activates kinase without phosphorylation which then phosphorylates (and activates) glycogen phosphorylase to break down glycogen -> glucose |
| glycogen storage disease | inherited (genetic) disorders caused by defects in enzymes required for break down/ synthesis of glycogen meaning that glycogen has abnormal structure or there is excessive accumulation |
| symptoms of glycogen storage disease | range from relatively mild (inability to exercise) to fatal in early childhood |
Created by:
kablooey
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