Flashcards in Glycogen, Lysosomes, FA, Lipids Deck (67)
Describe how glucagon & epinephrine (Beta) lead to activation of glycogen phosphorylase
Glucagon & epi (when bound to Beta receptor) lead to activation of adenylyl cyclase leading to increased cAMP causing action on protein kinase A => this along w/ Ca+-Calmodulin complex activates glycogen phosphorylase kinase which then stimulates glycogen phosphorylase to make glucose
How does epinephrine (alpha) activate glycogen phosphorylase?
binding causing ER to release Ca+ that will also activate the Ca+ - calmodulin complex leading to activation of glycogen phosphorylase kinase (both Ca+ & Ca+ - calmodulin complex activate independently) => glycogen phosphorylase kinase then activates glycogen phosphorylase
How does insulin promote glycogen storage &/or prevent its breakdown?
insulin (liver & muscle) bind to & activate tyrosine kinase receptor dimer receptor activates glycogen synthase & activates protein phosphatase (inactivates glycogen phosphorylase)
What are the 2 actions of protein kinase A in glycogen regulation?
promotes indirect activation of glycogen phosphorylase
directly blocks glycogen synthase
How does muscle get energy during exercise?
glycogenolysis to form G-1-P to G-6-P which is rapidly metabolized during exercise
Describe the cycle of producing & breaking down glycogen in the liver to maintain normal blood sugar
G-6-P is inside the cell as G-1-P then UDP-glucose pyrophosphorylase converts it to UDP glucose =>
At this point glycogen synthase convert it to glycogen for storage (insulin) => a branching enzyme leads to better storage of glycogen
As the body needs sugar, glycogen phosphorylase is revved up while glycogen synthase is inhibited (both via Protein Kinase A) to produce limit dextrin (4 G-1-P residues)=>
Limit dextrin is attacked by a debranching enzyme (4-a-D-glucanotransferase) resulting in moving 3 from branch to linkage =>
Another debranching enzyme (a-1,6-glucosidase) cleaves off the last glucose 1- phosphate on the branch
Large concept of glycogen storage then breakdown is the bonds
Branches have alpha (1,6) bonds for storage;
linkages have alpha (1,4) bonds
How is some glycogen degraded in the lysosomes?
the enzyme alpha-1,4-glucosidase
There are 12 types of glycogen storage diseases. What do all result in? (key to remembering main 4)
AR diseases that all result in abnormal glycogen metabolism & accumulation of glycogen w/in cells
Very Poor Carbohydrate Metabolism
(Von Gierke, Pompe, Cori, McArdle)
Young child with severe fasting hypoglycemia, increased blood lactate, uric acid & hepatomegaly. What enzyme is deficient? why is liver large? What is Tx?
Von Gierke's disease (type I)
Deficient in Glucose - 6- phosphatase;
hepatomegaly due to large amounts of glycogen in liver
Tx is frequent oral glucose/cornstarch & AVOID fructose & galactose
Infant dies & findings are cardiomegaly & other systemic findings leading to early death. What is the deficient enzyme? What tissues are most damaged?
Pompe's disease (type II)
Deficient in lysosomal alpha-1,4-glucosidase (acid maltase)
Pompe's trashes the Pump => heart, liver, muscle
Young child comes in with moderate fasting hypoglycemia, increased glycogen in the liver & hepatomegaly but normal lactate in blood. What enzyme is deficient? What physiologic process is still intact?
Cori's disease (type III)
Deficient in debranching enzyme (alpha-1,6-glucosidase);
gluconeogenesis is still intact
A child has increased glycogen in muscle associated with painful cramps. He/she knows to avoid strenuous exercise & lives a normal lifetime. What enzyme is deficient? Why must strenuous exercise be avoided?
McArdle's disease (type V) => McArdle's = muscle
deficient in skeletal muscle glycogen phosphorylase
glycogen cannot be broken down in muscle so cramps occur which pull in water causing lysis leading to myoglobin in serum & kidney that may cause RHABDOMYOLYSIS
What is the common result in all lysosomal storage diseases? How are they inherited?
Result in accumulation of abnormal metabolic products
All are AR except Fabry & Hunter which are XLR
What are the sphingolipidoses?
A young boy who's uncle (dead) & him share the same peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease. What is the deficient enzyme? inheritance? accumulated substrate?
Fabry disease => XLR
deficient of alpha-galactosidase A enzyme
Ceramid trihexoside accumulates
What is the most common lysosomal storage disease? What is its treatment?
Tx is recombinant glucocerebrosidase
A young child has hepatosplenomegaly, pancytopenia, aseptic necrosis of the femur, severe bone pain. On H&E, lipid laden macs are present that resemble crumpled tissue paper. What is the deficient enzyme? inheritance? accumulated substrate?
Gaucher disease => AR
Deficient in glucocerebrosidase (Beta-glucosidase)
Gaucher cells => lipid laden macs are present that resemble crumpled tissue paper
A young Ashkenazi Jew has a cherry red spot on macula. He/she also has hepatosplenomegaly & neurodegenerative disease that is getting worse. Foam cells are also present. What is the deficient enzyme? inheritance? accumulated substrate?
Niemann-Pick disease => AR
deficient in sphingomyelinase
A young Ashkenazi Jew has a cherry red spot on macula. He/she has progressive neurodegeneration w/ developmental delay but has no hepatosplenomegaly. What is the deficient enzyme? inheritance? accumulated substrate? What will be seen w/in the cell?
Tay-Sachs disease => AR
Defects in heXosaminidase A
GM-2 ganglioside accumulates
lysosomes w/ onion skin appearance
What is the key to differentiate Tay-Sachs from Niemann Pick disease?
Tay Sachs does NOT have hepatosplenomegaly
A young child has peripheral neuropathy, developmental delay. Globoid cells & optic atrophy are present on H&E & exam. What is the deficient enzyme? inheritance? accumulated substrate?
Krabbe disease => AR
Deficient in galactocerebrosidase
Galactoscerebroside, psychosine accumulates
A young child has early dementia & ataxia associated with central & peripheral demyelination. What is the deficient enzyme? inheritance? accumulated substrate?
Metachromatic leukodystrophy => AR
Deficient in arylsulfatase A
Cerebroside sulfate accumulates
What are the mucopolysaccharidoses?
Hurler & Hunter syndrome
A young child has developmental delay, hepatosplenomegaly & airway obstruction. On neuro exam, corneal clouding is seen. The patient also has gargoylism. What is the deficient enzyme? inheritance? accumulated substrate?
Hurler syndrome => AR
deficient in alpha-L-uduronidase
Heparan sulfate & dermatan sulfate accumulate
A young child has shown very aggressive behavior towards others & no treatments seem to work & no corneal clouding. A family history shows some men in his family also have the same aggressive behavior. What is the deficient enzyme? inheritance? accumulated substrate?
Hunter syndrome => XLR
deficient in iduronate sulfatase
heparan sulfate & dermatan sulfate accumulate
Other than family history, what is another way to differentiate the mucopolysaccharidoses?
Hurler has corneal clouding => Hunter does NOT
Long chain FA degradation requires what?
carnitine dependent transport into mitochondrial matrix
What is the result of carnitine deficiency?
inability to transport LC-FAs into mitochondria leading to toxic accumulation
causes weakness, hypotonia, & hypoketotic hypoglycemia