Lecture 11 Overview of CHO Metabolism II Part A Flashcards
What are the storage polysaccharides?
Why store glucose in polymeric form rather than in free form?
Stored in polymeric formed in order to maximize storage in smallest possible form while still ‘readily’ available.
* optimization by by degree of branching and chain length
* 2-3 times more branching than amylopectin
* uses much less space and holds less water than the same for free glucose (minimizing osmotic pressure differential in cell)
What is the purpose of glycogen?
efficient, quick-release storage of glucose
How much of liver and skeletal muscle weight is glycogen?
- up to 10% of liver weight
- ~1% muscle weight
What is the storage capacity of glycogen?
Uses energy to store up to ~100,000 glucose in 1 polymer in a symmetrical and mathematical fashion for optimization
What inhibits glycogenesis?
- glycogenolysis
- glycogen content of tissue (capacity reached)
What are the two forms of glycogen synthase?
- A (GYS1 gene)
- B (GY2 gene)
Where is the GYS1 gene for glycogen synthase expressed?
expressed everywhere (muscle, brain, kidney, adipose)
* more active (unphosphorylated)
* Used in rapid response to glucose fed state as well as in exercise
Where is the GY2 gene for glycogen synthase expressed?
Expressed only in the liver
* less active (phosphorylated)
* Used to ensure large pools of avaialble for blood glucose concentrations
Why is GY2 gene less active?
it is phosphorylated but also it has less affinity for UDP-glucose and is less sensitive to allosteric acitvation by G6P so it only responds to the more long term needs in order to ensure capacity is always at its height.
What stimulates glycogen synthase A and B?
insulin stimulates both forms → as glucose comes in insulin tell the system it has enough in the periphery so what is left can be sent to glycogen storage
What stimulate glycogenolysis?
Use of glycogen → stimulated by low blood glucose levels and glycogen phosphorylase is stimulated by glucagon and epinephrine
glycogen in the fed state
↑glycogenesis: If insulin and ATP present in high amounts insulin promotoes storage of glucose as glycogen
* liver has enough energy and circulating blood has adequate glucose
* Prefers to use G6P from gluconeogenesis
* lactate appears to be preferentially shunted to glycogen
glycogen in the fasting state
↑glycogenolysis: breakdown if liver needs energy or blood glucose is falling.
* liver is depleted of glycogen within 24hr of fasting
* When no exogenous Glc, glycogenolysis is stimulated by glucagon in the liver to supply plasma Glc
What are some common types in which glycogenolysis occurs?
essentially no exogenous glucose coming in for a while
* waking up
* exercise
* skipped lunch
Fate of glycogen breakdown in the liver vs. muscle
Fate and purpose of glycogen breakdown is different between the liver and muscle
* Liver: glycogen→G6P→blood glucose or ATP
* Muscle: glycogen→G6P→ATP
Why does muscle glycogen not contribute to blood glucose?
muscle does not have the enzyme G6Pase so it cannot convert G6P into glucose
In the liver when will glycogen be used for blood glucose vs. energy?
- Energy needed: If no other Glc available then liver derived G6P will go through glycolysis to supply ATP
- Energy not immediate: If energy is not need immediately &/or blood Glc is needed, liver derived G6P will be converted to Glc to supply blood circulation and be used by tissue
Glycogen storage disease Type 1
G6Pase deficiency
Inherited as an autosomal recessive genetic disorder. Glycogen storage disease type I (GSDI) is characterized by accumulation of excessive glycogen and fat in the liver and kidneys that can result in an enlarged liver and kidneys and growth retardation leading to short stature.
Mechanism for glycogenolysis in the liver
Allosteric Control
In the liver if glucose or energy (ATP) is needed quickly, glucagon (via glucagon receptors) & epinephrine (via beta-andrenergic receptors) induce cAMP response, which activates glycogen phosphorylase
acute phosphorylation induces response
Mechanism for glycogenolysis in skeletal muscle
phosphorylation control (energy requirements)
* rate of phosphorylation depends on the ratio of phophorylase A (more active/not sensitive to ATP) phosphorylase B (dephosphorylated form/less active)
* Efflux of calcium from muscle contraction (exercise) also activates phosphorylase kinase that in turn generates phophorylase A in order to stimulate breakdown of glycogen.
What is the gatekeeper for glycogen regulation/ metabolism?
G6P
Summary of glycogen metabolism/ regulation
- allosteric control of breakdown: G6P & ATP inhibit; AMP activates
- breakdown also controlled by phosphorylation (a & b)
- allosteric control of synthesis: G6P and insulin activate
- glycogenesis requires 2ATP/Glc
