Biochem Topic 12 Review PDF

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Biochem Revision Topic 12 - Metabolic Regulation What polymeric forms is glucose stored as? Glycogen in animals and many microorganism; starch in plants. What is the structure of glycogen? Large branched polymers of glucose. Glucose linked by α1-4 bonds with α1-6 branches. They are branched every 8-12 residues. Many non reducing ends. What is the function of glycogen? It serves as a reservoir of glucose to be mobilised when glucose is required. For example between meals or during a fast. During prolonged physical activity. How long is it before glycogen stores are exhausted in the human body? 12-24 hours during a fast, or during 1 hour of vigorous activity. Where is glycogen found? Found primarily in liver and skeletal muscle." Liver; serves as a reservoir of glucose and is readily converted into glucose and it is distributed in blood or other tissues. Skeletal muscle; converted into glucose 6-P and used in glycolysis to generate ATP to power muscle contraction. Why do cells store glucose in polymeric form rather than glucose? Osmotic pressure would be higher (roughly 0.4M). When stored as glycogen the concentration is less than 0.01μM as it is in an insoluble granule form and thus contributes little to osmolarity. Furthermore glucose stored as glycogen may not be utilised by glycolysis enzymes. What is the consequence for glycogen depletion in regards to fatty acids? Once glycogen is depleted, fatty acids cannot be converted to glucose, and fats can only be used by certain tissues. Therefore, once glycogen is depleted, cells that rely solely on glucose (like the brain) must be supplied with glucose. So it would then be generated by gluconeogenesis from noncarbohydrate sources such as protein and lactate. When does glycogen catabolism occur? When blood glucose levels are low. What three enzymes are used to release glucose units from the outer branches of glycogen? (1) Glycogen phosphorylase (2) Glycogen debranching enzyme (3) Phosphoglucomutase What is the function of glycogen phosphorylase and how does it work? It catalyses a reaction in which a α1-4 glycosidic linkage undergoes attack by an inorganic phosphate. This release terminal glucose residue from the non-reducing end as glucose 1-P. It acts repetitively to remove glucose from non-reducing ends and stops when it reaches a point of four glucose residues away from an α1-6 branch point. What is the debranching enzyme and how does it work?

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It shifts a block of three glucose residues from branch to a nearby non-reducing end (attached by an α1-4 linkage). It then cleaves the last glucose residue at branch point (α1-6 linkage). Then glycogen phosphorylase can degrade remainder of linear chain.

What is the function of phosphoglucomutase? It converts glucose-1P to glucose-6P What is the fate of glucose-6P? It is tissue dependent. In the liver the enzyme glucose 6-phosphotase (From GNG) converts glucose-6P to glucose. Glucose is then released into the bloodstream to maintain blood glucose levels." In skeletal muscle glucose cannot be synthesised as skeletal muscle does not contain glucose 6phosphotase. Glucose 6-P is exclusively catabolised in glycolysis to generate energy in muscle. Polymerisation of hexoses requires prior formation of what? Sugar nucleotides. Anomeric carbon of sugar is activated through a phosphodiester linkage. Sugar nucleotides are also important for polymerisation of sugars into disaccharides, starch, cellulose and synthesis of vitamin C. Why are sugar nucleotides used in biosynthetic reactions? (1) the nucleotide is an excellent leaving group (like a phosphate) (2) The nucleotide can act as a “tag” which enables cells to set aside a particular sugar for a particular purpose. (3) The nucleotide moiety can be recognised specifically by enzymes. (4) Net reaction for formation of sugar nucleotide has a large negative free energy change. (5) Therefore the formation of sugar nucleotides is irreversible, which contributes to the irreversibility of the pathways of which they are intermediates. How are sugar nucleotides formed? (1) Glucose is converted to glucose 6-P. (2) Glucose 6-P converted is converted to glucose 1-P by phosphoglucomutase. (3) Glucose 1-P converted to UDP-glucose by UDP-glucose pyrophosphorylase. What is the function of glycogen synthase? Catalyses the transfer of the glucose residue from the UDP-glucose to a non-reducing end of a glycogen chain. Requires a “primer” α1-4 polyglucose chain with at least four glucose residues glycogenin protein performs this function. It cannot make the α1-6 bonds at branch points of glycogen, this is performed by an enzyme. How does the branching enzyme work for chains greater than 11 glucose residues? Catalyses transfer of terminal fragment (6-7 glucose residues) from the non-reducing end of glycogen branch to the C6 hydroxyl group of a glucose residue at a more interior position in the same or another glycogen chain. What is the biological function of branching? Why not have just one long chain? Increases number of sites for glycogen phophorylase and glycogen synthase to function. Enables faster responses to changing BGL. Explain briefly the four metabolic pathways that affect blood glucose levels. (1) Glycolysis - producing energy under anaerobic conditions (2) Gluconeogenesis - producing glucose from non-carbohydrate sources once glycogen stores are depleted. (3) Glycogenolysis - release of glucose for ATP production (4) Glycogenesis - storage of energy rich glucose

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Regulation of the aforementioned pathways are required to ensure what? - Metabolites move through pathways in the correct direction. Changes in metabolite concentration can change the directionality of the pathways. - Rates of these pathways match demands of the cell." > ATP demand increases 100 fold in exercising muscle in seconds." > Proportions of carbs/fats/proteins vary with every meal." > Supplying of nutrients is intermittent - requires adjustments between meals and during starvation." > Wound healing requires huge amounts of energy and biosynthetic precursors. What is enzyme activity commonly regulated by? The number of enzyme molecules which can be altered by changing the rate of synthesis or degradation. " The catalytic activity of each molecule; allosteric alteration of an enzyme and covalent alterations of an enzyme (phosphorylation) Why is it the irreversible reactions in a pathway that are common points for regulation? Because regulation the reversible reactions would shut down both pathways. How does regulation of glycolysis and gluconeogenesis occur? By regulating the enzymes that catalyse the irreversible reactions. What is regulation based on? • The energy status of the cell. (When ATP is low glycolysis predominates and when ATP is high GNG predominates). • Blood glucose levels (When BGL is high glycolysis predominates, etc). Which molecules signal low energy status in a cell? AMP and ADP. Which molecules signal high energy status in a cell? ATP; citrate; fructose 1, 6 biphosphate; acetyl-CoA; long-chain fatty acids. Which organ detects low BGL? The pancreas Which hormones does the pancreas release in response to high or low glucose levels? High BGL - insulin" Low BGL - glucagon How does reciprocal regulation of GNG reaction 3 work? Molecules (AMP and ADP) that signal low cell energy levels activate glycolysis through PFK-1, therefore increasing ATP production. AMP inactivates GNG, as it is an energy expensive process. In turn molecules such as ATP and citrate signal high energy levels in the cell which inactivate glycolysis by inactivating PFK-1 as energy is not required. When is glycogen phosphorylase activated? When blood glucose levels are low; as it catalyses the breakdown of glycogen. What are the two forms of glycogen phosphorylase? (1) a; active form; unphosphorylated (2) b; inactive form; phosphorylated How does Glucagon work? Activate PKA - phosphorylates and inactivates glycogen synthase.

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How does insulin work? Activates PP1 - dephosphorylates and activates glycogen synthase.

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