Glycogen Catabolism Flashcards
(21 cards)
Who discovered glycogen?
The Cori’s 1925-1950
Nobel Prize in 1947 for glycogen metabolsim
What is the most significant feeder pathway into glycolysis?
Glycogen catabolism
-fructose, galactose, mannose, sucrose, lactose, trehalose, maltose also feed into glycolysis to be catabolised but most significant contributers are storage polysaccharudes - glycogen and starch
What is glycogen?
A very large polymer of glucose in (alpha1-4)(straight chain) and (alpha1-6)(kink on chain) linkage
- 12 tiers in mature glycogen with 55,000 glucose residues build on glycogenin protein
-20-40 particles come together - large alpha-rosettes of glycogen granules
What does glycogen do?
-Synthesised and stored in animal liver and skeletal muscle and other cell types and in m/o
-Readily mobilised storage form of glucose
-Plays role in maintaining blood glucose levels
-Liver glycogen - glucose resevoir- supplies blood glucose when needed
-Skeletal muscle glycogen - glucose quick source of engery used in less than 1 hr vigorous activity
What is the main enzyme in glycogen catabolism and how does this work?
Glycogen Phosphorylase
-Removes terminal glucose molecules from glycogen by adding a phosphate molecule (phosphorylating) to C1 of glucose molecule which breaks the bond between C1 and C4 and so released the glucose
-glucose is released as glucose 1 - phosphate
-Glycogen phosphorylase acts repetitively until it meets alpha 1-6 branch and stops working 4 glucose residues before the branch
What happens when glycogen phosphorylase comes into contact with alpha 1-6 linkage?
-Stops working 4 resides before branch
-Debranching enzyme removes 3 glucose residues before branch to another tier by transferase activity
-The alpha 1-6 glucosidase activity of ‘debranching enzyme’ cuts off glucose
What happens to the glucose 1-phosphate produced?
Phosphoglucomutase converts it to glucose 6-phosphate which can enter glycolysis
Glycogen storage diseases
-Affect enzymes degrading and synthesising glycogen e.g genetic mutations in glycogen phosphorylase, glycogen debranching enzyme, glucose 6 phosphatase
-Rare - usually inherited - AR
-Result in enlarged liver, muscle wasting (myopathy), metabolic problems
-Treatment- very low glucose and monitored carbs diet
Look at glycogen storage diseases
What is gluconeogenesis?
New genesis/ formation of glucose
Whta happens when glycogen/starch depleted and no dietary input of organisms?
-Need to synthesise glucose
-Organisms synthesise glucose from simple non-carbohydrate precursors
-Mainly in liver cytosol and in renal cortex and cells of small intestine
What are the main precursors for glucose synthesis?
3Cs - lactate, pyruvate, glycerol
-glucogenic aminio acids, particularly alanine and glutamine
-citric acid cycle intermediates especially oxaloacetate
(glucogenic- amino acids that can synthesise glucose)
What steps does glucogenesis have that are in glycolysis?
-Shares the 7 reversible steps of glycolysis, 2, 4-9
-The 3 irreversible steps of glycolysis, enzyme 1, 3, 10 are by passed in glucogenesis
What does glucogenesis use instead of enzymes 1, 3, 10?
3 complete different exergonic regulated pathways
Step 1 - to convert pyruvate to phosphoenolpyruvate - uses 2 enzymes pyruvate carboxylase and PEP carboxykinase - needs energy, 2xATP and 2xGTP for 2xPyruvate
Step 7 - Converts fructose 1,6 bisphosphate to fructose 6-phosphate using fructose 1, 6-bisphosphatase which removes a phosphoryl group from position 1.
Step 10 - coverts glucose 6-phosphate to glucose using glucose 6-phosphatase by removing a phosphoryl group at position 6.
Does glucogenesis produce or cost energy?
Costs energy as making 1 glucose from 2 pyruvates uses 4 ATP, 2GTP, and 2NADH
Steps in glycogen synthesis?
- glucose 6-phosphate isomerises to Glucose 1-phosphate catalysed by phosphoglucomutase
- a UDP nucleotide adds on to Glucose 1-phosphate - glucose 1-phosphate + UTP -> UDP-Glucose and releases 2 phosphates
- UDP-Glucose donates glucose to the non-reducing end of a growing glycogen chain catalysed by enzyme Glycogen Synthase
- The glycogen branching enzymes makes alpha 1-6 branches
What is the major regulated enzyme in glycogen synthesis?
Glycogen Synthase
What does glycogen synthesis start on?
A protein ‘primer’ called glycogenin
What can regulate metabolic enzzyme catalytic activity?
-Allosteric modulators change enzyme conformation and so turn enzyme activity on/off - major energy indicators like ATP, AMP, are often allosteric modulators
-Covalent modifications can regulate activity of emtabolic enzymes - phosphorylation and dephosphorylation
-Amount of enzyme
-Association of enzyme with regulatory proteins
-Sequestration of enzyme e.g away from its substrate in an organelle
What amino acid residues does phosphorylation on enzyme occur on?
Serine
Threonine
Tyrosine
Histidine
What are the major hormones controlling enzymes in metabolism?
insulin, glucagon, adrenaline
-all hormones act reversibly on specific proteins
