Chapter 24 Flashcards
Homopolymer
- A polymer made up of many copies of a single repeating unit
- A polymer made up of one type of monomer unit
Glycogen Overview
- Glycogen = highly branched homopolymer of glucose that is present in all tissues
- The largest stores of glycogen are in the liver and muscle
- Liver breaks down glycogen and releases glucose to blood to provide energy for the brain and RBC
- Muscle glycogen stores are mobilized to provide energy for muscle contraction
Glycogen Structure
- Structure of glycogen is a straight chain w/ alpha-1,4-glycosidic linkages between glucose molecules
- Branching will take place every 10th residue w/ an alpha-1,6-glycosodic bond
- The ends (or exterior) of chain are non-reducing w/ a free – OH group
Glycogen – Breakdown Overview
For the breakdown of glycogen, 4 enzymes are required: glycogen –> glucose-6-phosphate
- 1 enzyme is required to degrade glycogen and release glucose-1-phosphate
- 2 enzymes are required to remodel glycogen (on a bifunctional enzyme in eukaryotes
–> the enzymes ensure that glycogen remains a substrate and produces some free glucose (no phosphate)
- 1 enzyme converts the product of glycogen breakdown into a usable product ~ glucose-6-phosphate
Glycogen – Breakdown: Step 1
Glycogen phosphorylase = key regulatory enzyme that degrades glycogen from non-reducing ends of the glycogen molecule
- Glycogen phosphorylase catalyzes a phosphorolysis reaction that yields (produces) glucose-1-phospate
- Phosphorolysis reaction breaks down alpha-,1,4 glycosidic bonds using orthophosphate
- Phosphate gets attached to C-1 of glucose that is released
- Glucose-1-phosphate is then converted into glucose-6-phosphate by phosphoglucomutase
What is phosphorolysis?
The cleavage of a bond by orthophosphate, as in the degradation of glycogen to glucose 1-phosphate
Hydrolysis reactions use water to split bigger molecules into smaller ones, phosphorolysis reactions use phosphate instead for the same purpose
Glycogen – Breakdown: Step 2
During glycogen breakdown, a problem will arise ~ glycogen phosphorylase can’t cleave (split) 4 glucose resides near the branch point and can only cleave (split) alpha-1,4-glycosidic bonds (aka, it can’t leave the alpha-1,6 glycosidic bonds)
Solution: requires 2-additional enzymes ~ transferase and de-branching enzyme
- Transferase enzyme: shifts a small oligosaccharide near the branch point to a nearby chain, thereby making glucose moieties more accessible to the phosphorylase
- De-branching enzyme (alpha-1,6-glucosidase): will cleave the alpha-1,6-glycosidic bonds at the branch point, releasing a free glucose
Glycogen – Breakdown: Step 3
Phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate w/ the use of glucose-1,6-bisphosphate intermediate
- This reaction is important as glucose-6-phosphate is used in glycolysis
- Transfer for phosphoryl groups is facilitated by serine residues in enzyme. Phosphoryl group from serine in phosphoglucomutase enzyme active site is transferred from enzyme to the substrate, glucose-1-phosphate
- This generates a glucose 1,6-bisphosphate intermediate
- Phosphoryl group on C1 of substrate is transferred to serine residue of enzyme to restore enzyme to its initial state
- Reaction generates glucose-6-phosphate, which will be utilized in glycolysis
Glycogen – Breakdown: Step 4
The liver contains glucose-6-phosphatase, a hydrolytic enzyme
Glucose-6-phosphatase generate glucose from glucose-6-phosphate in liver
The free glucose is released into blood for use by other tissues, such as brain and RBC
Glucose-6-phosphatase is absent in most other tissues. Notably absent in muscle
Key regulatory enzyme for glycogen degradation = glycogen phosphorylase, which has two forms. What are the two forms and how do they differ?
- B-less active
- A-more active
A-form differs from B-form by the phosphorylation of a serine residue in A-form
Describe some of the difference between A-form and B-form of glycogen phosphorylase
A form and B form each display an R to T-state equilibrium
A-Form
- R-state is favored
- Serine phosphorylated
- Usually inactive b/c the equilibrium factors R-state
- Active site is unobstructed (accessible)
B-Form
- T-state is favored
- Serine unphosphorylated
- Usually inactive b/c the equilibrium factors T-state
- Active state is partial partially blocked by a regulatory structure
—> The regulatory site is site of glucose binding, which serves as an allosteric regulator of enzyme activity
Regulating Glycolysis – Liver Glycogen Phosphorylase
- Key role of liver is to maintain adequate blood glucose level
- Liver phosphorylase produces glucose for use by other tissues. This, the default state of liver phosphorylase is in A form in R state. In essence, liver phosphorylase is prepared to generate blood glucose unless signaled otherwise
- Glucose is a negative regulator of liver phosphorylase and a negative regulator/feedback inhibitor
- When there’s ample amounts of glucose, glucose binds to active site and shifts enzyme to T state, in active
- Hormonal regulation will also influence enzyme activity: Glucagon and epinephrine will activate enzyme by signaling phosphorylation of serine residue
- Insulin will deactivate enzyme by signaling dephosphorylation of serine residue
Regulating Glycolysis – Muscle Glycogen Phosphorylase
- Muscle phosphorylase is regulated by intercellular energy charge
- In muscle, default form of phosphorylase is B form in T state
- When energy is needed in cell, as signaled by increase in concentration of AMP, the phosphorylase binds AMP which stabilizes R state
- When there is lots of energy in cell, which is signaled by ATP and glucose 6-phosphate
- Binding stabilizes the T state. The T state of phosphorylase is stabilized by ATP and glucose-6-phosphate
Biochemical Characteristics of Muscle Fiber Types Differ
The biochemical characteristics of muscles will differ by fiber types and the muscle is composed of several fiber types:
- Type I, or slow-twitch fibers rely primarily on cellular respiration for ATP generation
- Type IIb (type IIx), or fast-twitch fibers rely primarily on lactic acid fermentation for ATP generation
- Type IIa fibers have biochemical characteristics that are intermediate between the other fiber types
- Type IIb fibers are rich in glycogen phosphorylase
What is phosphorylase kinase? Describe how phosphorylation of phosphorlyase kinase works
Glycogen phosphorylase phosphorylation at the serine residue requires a kinase ~ phosphorylase kinase phosphorylates glycogen phosphorylase
Phosphorylase kinase:
- is a large multimeric enzyme with a mass of ~1300 kDa and multiple subunits
- exists in two forms: A less active, B more active
- The A-form differs from B-form by the phosphorylation of serine residue 14
- Phosphorylase kinase is regulated by phosphorylation & calcium binding
- Phosphorylation is stimulated by hormones glucagon and epinephrine
- Phosphorylation alters the active site so that the alpha helices that partially block the active site in the B form are removed
- Phosphorylase kinase is phosphorylated by PKA
- The delta δ (delta) subunit of phosphorylase kinase is the calcium sensor calmodulin
- Phosphorylase kinase is maximally activated when phosphorylated and bound to calcium
