FORM & FUNCTION (Glycogen) Flashcards
glucose must be maintained at
-5mM
*hormonal control: insulin and glucagon
excess glucose
-stored as glycogen
1. Liver (up to 10% weight)
2. Muscle (up to 1-2% weight)
*muscle pool is 4-6x of liver
glycogen
-60% water (heavy)
-limit to how much the body can store
-polyssaccharide
-can contain 1,000 to 12,000 glucose molecules
glycogen synthase
-creates alpha-1,4 linkages
branching enzyme (transglycosylase)
-creates alpha-1,6 linkages
>removes linear linkage=increases solubility
mutations in glycogen synthase or branching enzymes
-lead to glycogen storage disease
glycogenesis
- Glu to Glu-6-P (by hexokinase or glucokinase)
- Glu-6-P: glycolysis or phophoglucomutase forms Glu-1-P
- UTP converts it to UDP-glucose=activated glucose=high energy
- Glycogen synthase form glycogen
*glucose by itself is low in energy requires activation to form glycogen (costs energy (UTP) to make glycogen)
glycogen branching
-when 8-14 alpha-1,4 linked glucose are created = re-organized into 1,6-linkage = increases solubility
insulin
-regulates/controls glycogenesis
-activates glycogen synthase THROUGH protein phosphatase 1
insulin (steps)
- Usually glycogen synthase is inactive (phosphorylated form)
- Insulin activates protein phosphatase 1 to dephosphorylate glycogen synthase
- Now activated (dephosphorylated form)
glycogen synthesis regulation
- High blood glucose
- Insulin release
- Glycogen synthase activation
- Excess glucose stored as glycogen (contributes to decrease in blood glucose)
glycogen reserves (major role)
- Maintain blood glucose (liver)
-provide energy supply for RBC and brain (fat cannot cross BBB) - Metabolic energy (muscle)
*rapidly movilized and broken down (faster than fat)
*can be used aerobically or anaerobically to generate ATP (via glycolysis)
glycogenolysis mechanism (liver)
- Glucagon or catecholamines
- Bind to receptor in liver PM, get secondary messenger cAMP
- Protein kinase A is activated and activates (add P) phosphorylase kinase
- Inhibits glycogen synthase (removes P)
- Activates glycogen phophorylase (adds P)
- Breaks down 1,4 linkage (get glucose 1-phosphate molecule)
glucagon
-released from pancreas due to low glucose signals
catecholamines
-released form adrenal gland as a response to stress or exercise
Ex. NE or E
phosphorylase kinase
-activated by protein kinase A
-inhibits glycogen synthase
-activates glycogen phophorylase (adds P)
glycogen phosphorylase
-breaks down 1-4 linkage (forms glucose 1-phosphate)
alpha 1,6 linkage breakdown
-debranching enzyme: alpha-1,6 glucosidase
1. Transfer a block of 3 residues to the non-reducing end
2. Cleaves single remaining alpha-1,6 linkage to directly yield glucose (goes to blood or glycolysis for ATP)
liver glycogen breakdown overview
-mostly alpha 1,4-linkage breakdown via glycogen phosphorylase (90%)
>glucose 6-P can be turned to glucose via Glucose 6-phophatase
-if go to glucose, can enter blood via GLUT2 (bi-directional transport)
-10% alpha-1,6 linkage breakdown via debranching enzyme (glucose to blood of glucose to glucose 6-P)
role of liver glycogen
- Glucose release into blood (predominant function)
- Fuel for glycolysis
maintaining blood glucose
-90% of glycogen goes to Glucose 6-P (phosphorylation traps it inside the cell)
-transported to ER where glucose-6-phosphatase is located to dephosphorylate glucose (‘untraps’ it)
*bulid up of concentration gradient controls glucose flux out of liver
glycogenolysis mechanism (muscle)
- Catecholamines released form adrenal gland in response to stress or exercise (no glucagon receptor)
- cAMP to protein kinase A
- Inhibits glycogen synthase
- Activate glycogen phosphorylase
*muslce contraction releases calcium, which directly activates phophorylase kinase without cAMP
muscles lack
-glucose 6-phosphatase and glucose 6-P is always trapped inside glycolysis
role of muscle glycogen
-muscle GLUT4 transporter does not transport glucose back to blood
*used directly for energy
-can NOT contribute to blood glucose levels
-hexokinase ‘converts’ glucose (from the blood or glycogen breakdown) to glucose 6-P
