Exam 1 Glucagon Metabolism Flashcards
what are the four steps of glycogenesis?
hexokinase (HK IV in hepatocytes), phosphoglucomutase, UDP glucose pyrophosphorylase, and glycogen synthase
hexokinase rxn
glucose + ATP —> glucose-6-phosphate + ADP
phosphoglucomutase rxn
glucose-6-phosphate <—> glucose-1-phosphate
Glycogen (Getting Started)
- glycogen synthase cannot couple UDP-glucose to glucose
- UDP-glucose + glucose —> maltose
- glycogen synthesis must be primed: glycogen performs the addition of glucose to one of its own tyrosine residues (self-glycosylation) (uses UDP-glucose as a substrate): produces an 8(ish) glucose-unit chain attached to Tyr194
Branching
- transfer of a segment of G-7 glucose units from C4-OH to a C6-OH
- catalyzed by amylo(alpha-1,4 and alpha-1,6) transglycosylase or branching enzyme
- branch can be placed no closer than every 4th glucose; will usually be about 10 units between branches
why is branching important?
- compacts polymer structure
- each C4-OH is a place for glycogen phosphorylation
what is glucogenolysis?
mobilization of glucose from internal glucose stores (contrast with digestion of dietary starch)
dietary starch digestion
- all steps are hydrolytic
- alpha-amylase: (salivary glands and pancreatic duct —> duodenum) hydrolyzes alpha-1,4 glycosidic bonds
- endoglycosidase: anywhere glycosidic linkage present can be hydrolyzed
starch —> maltose + maltotriose (together = maltase) - debranching enzyme: alpha-1,4 to alpha-1,4 gluconotransferase, alpha-1,6 glucosidase; both activities in one enzyme removes limit branch (4 units left, so units of 3 gets transferred to main chain and alpha-1,6 glucosidase removes last unit
- glucose uptake by intestinal epithelial cells (apical membrane pointed to intestinal lumen)
- active transport: Na+/ glucose symporter (SGLT1), glucose released to the blood, done by facilitated diffusion, GLUT2 in the basolateral membrane
dietary starch digestion note
- no phosphorylation involved in this process; facilitates passage of glucose to circulation
- conserves ATP
- because no glucose-6-phosphatase, ensures glucose doesn’t get trapped in IEC (intestinal epithelial cells)
- dietary upake = largely regulated
Glycogenolysis: release of glucose-6-phosphate from stored glycogen: general features
- occurs primarily by phosphorolysis
- occurs one glucose unit at a time from a non-reducing end
- tightly reduced!!
Glycogenolysis: release of glucose-6-phosphate from stored glycogen: reactions
- glycogen(n) + Pi —> glycogen(n-1) + glucose-1-phosphate
- catalyzed by glycogen phosphorylase
- phosphorolysis prevents the need to rerun the hexokinase rxn (conserves ATP)
- keeps glucose confined within a cell (skeletal muscle- always, liver- as appropriate) - branch points removed by debranching enzymes
- alpha-1,4 —> alpha-1,4 gluconotransferase
alpha-1,6 glucosidase (only hydrolytic step) - glucose-1-phosphate <—> glucose-6-phosphate
- catalyzed by phosphoglucomutase
what is the primary target during the regulation of glycogenesis?
glycogen synthase
primary mechanism of regulation of glycogenesis
phosphorylation/dephosphorylation
- glycogen synthase dephos. (active) + ATP —> glycogen synthase phosp. (inactive) + ADP
- glycogen synthase phosp. (inactive) + H20 —> glycogen synthase dephos. (active) + Pi
phosphorylation mechanisms of the regulation of glycogenesis
GREATER EXTENT OF PHOSPHORYLATION = GREATER DECREASE IN ACTIVITY
- cycic AMP-dependent: response to glucagon in liver, response to epinephrine in hepatocytes/liver cells/skeletal muscle cells
- diacylglycerol-dependent (also involves inositoltriphosphate): also part of liver response to epinephrine
dephosphorylation mechanisms of the regulation of glycogenesis (kinases)
- protein kinase A (cyclic AMP)
- phosphorylase kinase (cyclic AMP)
- Ca2+/calmodulin-dependent protein kinase
