Chapter 14 Flashcards
What is glycogen?
branched polymer of glucose
storage form of glucose in cytoplasm
synthesis and degradation largely in liver and skeltal muscle
–cardiac muscle and kidney store in smaller quantities
How can glycogen be stored?
single granules: skeletal muscle
–stored as energy for muscle contraction
fast twitch: glucose converted primarily to lactate
slow twitch: glucose is completely oxidized
clusters of granules: liver
–stored to be mobilized during hypoglycemia
What is the structure of the granule?
central protein core (glycogenin) with polyglucose chains radiaing outward
–only linear chains: highest density of glucose near core
–branched: highest density of glucose at periphery; allow more rapid release of glucose
How is glycogen synthesized?
core protein glycogenin
–begins with glucose 6 phosphate
converted to glucose 1 phosphate and activated UDP-glucose for addition to glycogen chain by glycogen synthase
–glycogen synthase is rate limiting enzyme
What is the function of glycogen synthase? What activates and inhibits it?
forms alpha 1,4 glycosidic bonds in linear glucose chains of granule
–activated by: insulin in the liver and skeletal muscle
–inhibited by glucagon and epinephrine in the liver and epinephrine in skeletal muscle
What is the function of branching enzyme (alpha 1,4:alpha 1,6 transferase)?
introduces alpha 1,6 linked branches
–hydrolyzes one of the alpha 1,4 bonds to release a block of oligoglucose, which is moved and added in different location
–forms an alpha 1,6 bond to create a branch
What is the rate limiting enzyme of glycogenolysis?
glucagon phosphorylase
–breaks alpha 1,4 glycosidic bonds using Pi
–glucose 1 phosphate formed is converted to glucose 6 phosphate by same mutase used in glucose synthase
–cannot break alpha 1,6 bonds; stops when it nears outermost branch points
What activates and inhibits glycogen phosphorylase?
Liver:
activated: epinephrine, glucagon
inhibited by: insulin
Muscle:
activated by: epinephrine, AMP, Ca2+ (through calmodulin)
inhibited by: inulin and ATP
What is the function of debranching enzyme (glucosyl alpha 1,4: alpha 1,4 transferase and alpha 1,6 glucosidase)?
deconstructs branches in glycogen
–breaks an alpha 1,4 bond adjacent to branch point and moves it to small oligoglucose chain released to the exposed end of the other chain
–forms new alpha 1,4 bond
–hydrolyzes alpha 1,6 bond, releasing the single reisdue at the branch point as free glucose (only free glucose produced directly in glycogenolysis)
What is von Gierke disease?
glucose 6 phosphatase deficiency
fasting hypoglycemia, lactic acidosis, hepatomegaly
–glycogen deposits in the liver (G6P stimulates glycogen sythesis and glycogenolysis in inhibited)
–hyperuricemia predisposing to gout; decreased Pi causes increased AMP, which is degraded to uric acid–lactate slows uric acid excretion in the kidney
–hyperlipidemia with skin xanthomas; elevation of triglycerides (VLDL)
–fatty liver
–ingestion of galactose or fructose and adminstration of glucagon and epinephrine causes no increase in blood glucose
What is myophosphorylase deficiency?
McArdle deficiency
muscle glycogen phosphorylase deficiency
unable to properly break down glycogen to G6P in muscles
symptoms:
–exercise intolerance during initial phase of high intensity exercise
–muscle cramping
–possible myoglobinuria
–recovery or second wind after 10-15 minutes of exercise
ameliorated by drinking sucrose rich soft drinks–provides dietary glucose for muscles to use
What is hepatic glycogen phosphorylase deficiency?
Hers disease
relatively mild becuase gluconeogensis compensates for lack of glycogenolysis
symptoms: hypoglycemia, hyperlipidemia, hyperketosis are mild
hepatomegaly, growth retardation in early childhood
What is lysosomal alpha 1,4 glucosidase deficiency?
Pompe disease
deficient enzyme normally reisdes in lysosome
responsible for digseting glycogen-like material accumulating in endosomes (inclusion bodies)
tissues most severely affected arethose that normally have glycogen stores
infantile onset: massive cardiomegaly–cause of death by 2 years of age
symptoms: slowly progressing muscle weakness involving arms and legs, difficulty breathing, enlarged liver
What is Andersen disease?
What is Cori disease?
What is gluconeogenesis?
promoted by glucagon and epinephrine and inhibited by insulin
–gluconeogenesis when glycogen reserves drop after 12 hours
after 24 hours, it is sole source of glucose
What are important substrates for gluconeogenesis?
glycerol 3 phosphate (from triacylglycerol in adipose)
lactate (from anaerobic glycolysis)
gluconeogenic amino acids (protein from muscle)
What are the ketogenic and glucogenic amino acids?