Flashcards in glycogen and pentose phosphate pathway Deck (28)
fates of glucose
glycolysis, glyogen synthesis/storage or pentose phosphate pathway to generate NADPH and ribose sugars. The later 2 are active when glucose is present in excess of what is needed for glycolysis
Describe the structure of glycogen and why this is important
highly branched polymer of glucose monomers. Found primarily in liver and muscle
what controls glycogen breakdown
insulin and glucagon
major sites of glycogen storage
liver and skeletal muscle- glycogen in muscle must be released as lactate and synthesized into glucose by liver (cori cycle) b/c muscle lacks glucose-6-phosphatase
what is the building block of glycogen and how is it synthesized
uridine diphosphate (UDP)-glucose - glucose-6-phosphate > glucose-1-phosphate > UDP-glucose.
glycogen synthase function
transfers UDP-glucose to growing glycogen chain- UDP-glucose is transferred to hydroxyl group of glycogen to form alpha 1,4 glycosidic linkage. UDP is displaced and released. Only adds glucose residues if polysaccharide chain haas more than 4 glucose residues.
What forms he initiating site for glycogen synthesis
glycogen branching enzyme function
After glycogen synthase has added 11 glucose residues, branching enzyme transfers 6 or 7 glucose residues from a chain to an internal site to form α-1,6-linkages that produces a branch point in the growing polymer of glucose molecules. The new branch point must be at least 4 residues away from a pre-existing branch point
Result of abnormal glycogen branching
glycogen breakdown is slower which can result in hypoglycemia during fasting or reduced exercise tolerance.
steps in glycogen degradation
1. release of glucose-1-phosphate from glycogen. 2. remodeling of the remaining glycogen to permit further degradation. 3. conversion of glucose-1-phosphate into glucose-6-phosphate for further metabolism or export from the cell.
glycogen phosphorylase function
catalyzes the cleavage of glycogen to glucose 1-phosphate. Key regulated enzyme in glycogenolysis. Stops when it reaches 4 residues away from alpha-1,6-glycosidic bond branch point
debranching enzyme function
shifts a block of 3 glycosyl residues from one outer branch to the other, converting the branched structure into linear structure so that glycogen phosphorylase can continue
Function of glucagon or epinephrine in glycogen synthesis/breakdown
glucagon or epi activate protein kinase A > phosphorylates phosphorylase kinase b converting it to phosphorylase kinase a (active) > this phosphorylates glycogen phosphorylase b (inactive) to the a form (active) > glycogen phosphorylase a begins glycogen breakdown
function of insulin in glycogen regulation
insulin causes de-phosphorylation of glycogen phosphorylase (via phosphoprotein phosphatase 1, PP1) and of phosphorylase kinase (via protein phosphatase), ultimately causing glycogen synthesis
liver and skeletal muscles role in glycogen synthesis and degradation
In muscle, glycolysis and the TCA cycle/electron transport supplies ATP, and the rate of these pathways increase as the muscle works harder. The liver’s role is to maintain a constant level of glucose by producing glucose when other tissues demand it, and storing it when it is provided in excess by the diet.
regulation of glycogen in fed state
glycogen synthase is allosterically activated by glucose-6-phosphate when it is present at elevated concentrations following a meal. In contrast, glycogen phosphorylase is allosterically inhibited by glucose-6-phosphate as well as by ATP. In liver, glucose-6-P serves as the key allosteric inhibitor of glycogen phosphorylase.
regulation of glycogen in muscle via calcium
During muscle contraction, membrane depolarization promotes calcium release. Calcium binds to calmodulin and the complex activates a phosphorylase kinase which phosphorylates glycogen phosphorylase, activating it, leading to glycogen degradation.
regulation of glycogen in muscle via AMP
AMP binds to the inactive glycogen phosphorylase and allosterically activates it without the need for phosphorylation. This leads to greater glucose release from glycogen during vigorous exercise where AMP levels rise.
regulation of glycogen synthase
2 forms: The active form, a, is in the de-phospho form. Glycogen synthase a is converted to b (inactive) by phosphorylation, and the level of inactivation is proportional to the number of phosphate groups attached. The de-phospho form can be activated by allosteric activator, glucose-6-phosphate
In liver, which enzyme catalyzes dephosphorylation of glycogen synthase
protein phosphatase 1
How does glucose-6-phosphate activate glycogen synthase b
binds to allosteric site and makes the enzyme a better substrate for dephosphorylatin by PP1
hormonal regulation of glycogen synthase
Epi and glucagon: activate protein kinase A which phsophorylates and inactivates glycogen synthase. Insulin: activates PP1 and inactivates GSK3, which stimulates glycogen synthesis
glucagon regulation of glycogen in liver
low blood glucose > glucagon release > activates glycogen phosphorylase kinase in liver > converts glycogen phosphorylase b (inactive) to a (active) >release of glucose into blood. When blood glucose returns to normal > glucose enters hepatocytes > glucose binds allosteric site on glycogen phosphorylase > conformational change > phosphatase removes phosphate from phosphorylase a converting to to inactive glycogen phosphorylase b
Functions of pentose phosphate pathway
produces NADPH for synthsis of fatty acids and steroids (especially in mammary gland, adrenal cortex, etc), produces ribose-5-phosphate for nucleotide synthesis and glycolytic intermediates.
Location of enzymes in pentose phosphate pathway
phases of pentose phosphate pathway
oxidative - NADPH generating. Non-oxidative- ribose-5-phosphate and glycolytic intermediate generating.
Key steps of pentose phosphate pathway
glucose-6-phosphate dehydrogenase catalyzes the first rxn (key committed, and rate limiting) which generates first NADPH.