Glycogen Metabolism Flashcards
What form of glucose can be used to begin glycogen synthesis?
- glucose-1-phosphate
- G1P can be generated from G6P (glucose to G6P via hexokinase/glucokinase)
How can galactose join the glycogenesis pathway?
- galactose to galactose-1-phosphate (via galactokinase)
- galactose-1-phosphate to G1P (via galactose-1-P uridyltrasnferase)
What is the building block of glycogen? How is it formed?
- building block is UDP-glucose
- it is generated from glucose-1-phosphate (this reaction generates a pyrophosphate (PPi) and requires UTP)
Which enzyme converts UDP-glucose into glycogen? What’s the mechanism for glyogenesis?
- glycogen synthase takes UDP-glucose and forms glycogen + UDP
- glycogen synthase attaches UDP-glucose molecules to glycogen in an alpha-1,4 linkage pattern
Which accessory enzyme is involved in glycogenesis? What’s its mechanism?
- branching enzyme occasionally adds a UDP-glucose in an alpha-1,6 linkage pattern to form a new branch
- (links along a branch have alpha-1,4 bonds; new branches have alpha-1,6 bonds)
How is glycogenesis regulated?
- the enzyme glycogen synthase is activated by insulin and deactivated by glucagon
- glucagon deactivates via phosphorylation; insulin activates via dephosphorylation
Which enzymes are involved in glycogenolysis? What do these reactions require to break glycogen into glucose?
- glycogen phosphorylase and debranching enzyme (alpha-1,6-glucosidase)
- these reactions require inorganic phosphate (Pi)
- (converts glycogen back into glucose-1-phosphate)
How is glycogenolysis regulated?
- glycogen phosphorylase is activated by glucagon (in the liver), epinephrine, and AMP (in muscle), and is inactivated by insulin
- (activated in phosphorylated form, deactivated in dephosphorylated form - the opposite of glucagon synthase)
After glycogenolysis, glucose-6-phosphate (from glucose-1-phosphate) is formed - what happens next?
- in the LIVER (and kidneys when starving), G6P is used to make glucose via gluconeogenesis to make fuel for the body
- in other cells, G6P enters glycolysis to generate ATP to meet the cells’ own needs
Why is glucose stored as glycogen and not as itself?
- because glucose is way too osmotic to be stored in cells!
- (glycogen is also very osmotic, and so not much can be stored - the best storage unit is triglycerides as these are nonpolar and not osmotic)
What’s the purpose of forming branched molecules of glycogen?
- branching increases water solubility (easily dissolved in cells)
- branched glycogen has many terminal glucoses (where as a linear molecule would only have one) and it is at these terminal glucoses where glycogenolysis acts. this allows rapid access to energy in times of emergency
What results in a glycogen storage disease? How many glycogen storage diseases are there? How can these be organized? What are the four main diseases?
- abnormal glycogen metabolism results in an accumulation of glycogen in the cell’s cytoplasm
- there are 12 types; 3 categories (hepatic, myopathic, and miscellaneous)
- four main types are due to “Very Poor Carbohydrate Metabolism” (Von Gierke, Pompe, Cori, and McArdle diseases); all are autosomal recessive
Type I Glycogen Storage Disease
- Von Gierke disease; hepatic type
- deficiency in glucose-6-phosphatase
- results in severe fasting hypoglycemia, hepatomegaly due to increased glycogen storage
Type II Glycogen Storage Disease
- Pompe disease; miscellaneous type
- deficiency in lysosomal alpha-1,4-glucosidase (acid maltase) (small amounts of glycogen are degraded into the lysosomes with this enzyme)
- results in glycogen deposition in virtually every organ, but especially the heart (leads to cardiomyopathy)
- most patients die within 2 years from the heart complications
Type III Glycogen Storage Disease
- Cori disease; (mild) hepatic type
- deficiency in debranching enzyme (alpha-1,6-glucosidase)
- a much milder form of type I
