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WEEK 9:
Carbohydrates 1: Glucose uptake and storage
| Question | Answer |
|---|---|
| metabolic pathways? | branched or interconnected enzymatic reactions (catabolic or anabolic) producing specific products |
| metabolites | substrates, intermediates and products |
| where do metabolic reactions take place | reactions can be compartmentalised (in eukaryotes) |
| transport systems | move metabolites between organelles, acting as control points |
| catabolic | breaks down |
| anabolic | builds |
| normal range for blood glucose | 4-8mM |
| glucose enantiomers | D and L |
| glucose anomers | alpha and beta |
| in solution, what form is glucose in equilibrium with | 6 membered ring (glucopyranose) |
| why does glucose form alpha and beta anomers in solution | C1 is asymmetric |
| furanose | 5 membered ring |
| how many monosaccharides do oligosaccharides have | 3-10 |
| where does final digestion occur | mucosal cells |
| ATP dependent Na+ co-transporter | glucose coupled to sodium, goes against concentration gradient and found in intestinal epithelial cells |
| Na+ independent (passive) transport | glucose moves down concentration gradient |
| disruption of glycogen metabolism can cause what | glycogen storage diseases (GSDs) |
| role of glycogen in muscles | main fuel reserve for ATP synthesis |
| amount of glycogen in muscles | 400g (1-2% fresh weight) |
| role of glycogen in liver | mobilisation of glycogen helps maintain blood glucose levels (5mM) |
| amount of glycogen in liver | 100g (10% fresh weight) |
| what creates chains in glycogen | alpha (1-4) glycosidic bonds |
| what creates branch points in glycogen | alpha (1-6) glycosidic bonds |
| glucose-1-phosphate (G1P) | initial substrate and product for glycogenesis/glycolysis |
| what is G1P formed from | glucose-6-phosphate using phosphoglucomutase |
| limit dextrin | enzymes making and breaking down glycogen need a minimum of 4 glucose residues to bind |
| glycogenin | enzyme needed as a primer to form initial 8-glucose chain |
| what is UDP-glucose formed from | glucose-1-phosphate and UTP |
| how are glycogen chains extended | via glycogen synthase using UDP-glucose to form alpha 1-4 linkages |
| how are glycogen branches extended | by adding transferase to break the chain and reattach those parts upstream as alpha 1-6 linkages |
| glycogen phosphorylase | enzyme which breaks down glycogen into glucose-1-phosphate |
| role of glycogen phosphorylase in glycogenolysis | cleaves alpha 1-4 bond of terminal glucose from glycogen and adds Pi to release glucose-1-phosphate until only 4 glucose units remain on branch |
| reaction for glycogenolysis | (Glucose)n + Pi → (Glucose)n-1 + glucose-1-phosphate |
| glycogen de-branching enzyme for glycogenolysis | has two active sites (transferase and glycosidase) |
| transferase active site in glycogenolysis | 3 of the 4 remaining units on the branch are moved to the end of the main chain |
| glycosidase active site in glycogenolysis | removes single remaining sugar on the branch via hydrolysis of the alpha 1-6 bond |
| order of enzymes in glycogenolysis | glycogen phosphorylase, transferase, glycosidase |
| describe glycogenolysis/glycogenesis in the liver | synthesis increases in well-fed state and breakdown increases during fasting |
| describe glycogenolysis/glucogenesis in muscles | synthesis increases in rest period and breakdown increases during exercise |
| types of glycogen regulation (2) | hormonally and allosterically |
| hormonal regulation in glycogen | phosphorylation/ dephosphorylation of glycogen synthase and glycogen phosphorylase |
| allosteric regulation of glycogen enzymes | molecules bind to allosteric sites of glycogen phosphorylase and glycogen synthase |
| hormonal regulators (3) | insulin. glucagon and adrenaline |
| glucogenic hormones | adrenaline and glucagon |
| how do adrenaline and glucagon work | act through second messenger to increase glucose levels |
| what does adrenaline work on | both liver and muscle |
| what does glucagon work on | only liver |
| explain the second messenger model effect when blood glucose is high | adrenaline and glucagon bind to receptors which increases cAMP inside cells. Increased cAMP activates PKA. PKA phosphorylates glycogen synthase. Glycogen synthase becomes inactivated and glycogen phosphorylase = activated |
| explain the second messenger model when blood glucose is low | insulin binds to receptors which activates PP1 and inactivates PKA. PP1 dephosphorylates glycogen synthase and inactivated PKA cannot phosphorylate glycogen synthase. This activates the glycogen synthase and inactivates glycogen phosphorylase |
| dephosphorylated glycogen synthase | active form |
| phosphorylated glycogen synthase | inactive form |
| phosphorylation at multiple sites leads to what | stronger inactivation of glycogen synthase |
| what does protein phosphatase 1 (PP1) do | dephosphorylates glycogen synthase |
| what does protein kinase A (PKA) do | phosphorylates glycogen synthase |
| how is glucose-6-phosphate an allosteric activator in glycogen synthase | binds to allosteric site on glycogen synthase and increases activity even if glycogen synthase is inactive |
| what happens when glycogen phosphorylase is active | breaks down glycogen into G1P |
| inactive glycogen phosphorylase | glycogen phosphorylase b |
| active glycogen phosphorylase | glycogen phosphorylase a |
| how is glycogen phosphorylase activated | through second messenger model, PKA phosphorylates kinase which phosphorylates glycogen phosphorylase b into glycogen phosphorylase a |
| how is glycogen phosphorylase inactivated | through second messenger model, PP1 dephosphorylates glycogen phosphorylase a into glycogen phosphorylase b |
| allosteric inhibitors of glycogen phosphorylase | ATP, G6P |
| allosteric activators of glycogen phosphorylase | AMP (in muscles only) |
| allosteric regulation | faster response (ms) and can override hormone-mediated covalent regulation (eg exercise after eating) |
| high energy state | G6P and ATP inhibit glycogen phosphorylase, G6P activates glycogen synthase so synthesis increases |
| low energy state | AMP activates muscle glycogen phosphorylase so breakdown increases |
| in muscle, what is glycolysis activated by | calcium |
| explain the link between glycolysis and calcium | calcium binds to and activates calmodulin subunit of glycogen phosphorylase kinase b which activates it and can then phosphorylate glycogen phosphorylase |
| describe GSD | abnormal structure of excessive accumulation of glycogen |
| symptoms of GSD | mild (inability to exercise) to fatal in early childhood |