M104 T2 L7 Flashcards
In what form are polysaccharides stored in the body and where?
stored in granules
predominantly in liver and muscle
as an E reserve
From what process and product is glycogen formed?
glycogenesis
dietary glucose
What is the role of liver glycogen?
to maintain plasma glucose levels between meals
What is the role of muscle glycogen?
to sustain muscle contraction
What happens to glycogen between meals?
it is degraded in the liver
by the glycogenolysis pathway to produce glucose-1-phosphate
or it is broken down in muscle to provide the E to support muscle contraction
What happens to glucose-1-phosphate when it is converted from glycogen in the liver?
it can be converted to free glucose and exported into the bloodstream to maintain plasma glucose levels
What percentage of the weight of the liver and of the muscle comes from glycogen when in fed state?
liver - 10%
muscle - 2%
What percentage of human body weight is made up of muscle and of the liver?
muscle - 40%
liver - 2.5%
Overall, is more glycogen stored in muscle tissue or in the liver?
muscle tissue
40% of body weight x 2% = 0.8
liver: 2.5% x 10% = 0.25
Can the liver sustain glucose metabolism for 24 hours?
no - it contains less glycogen than is required to
it therefore requires de novo synthesis by gluconeogenesis
In what form is glycogen stored in the body?
found in the form of granules within cells
What is the structure of glycogen?
highly branched consists of (α-1,4) linked glucose molecules with an (α-1,6)branch every 8-14 glucose residues
What is an imporant structural feature of glycogen and why?
a large number of ends at which phosphorylase and glycogen synthase can act to ensure rapid breakdown and resynthesis
How many glucose residues does it take to come across an (α-1,6) branch?
every 8-14 glucose residues
How are glycogen molecules linked?
(α-1,4)
Where si the branch on glycogen molecules?
(α-1,6)
Which linkages are used to form glycogen?
α-D-Glucose
What are the two linkages used to form glycogen?
α-1,4 linkage
α-1,6 linkage
What happens in cells in times of metabolic need?
mobilisation - they switch on the breakdown of stored glycogen very rapidly using a combination of signals
the breakdown products meet different needs in liver and muscle
What is the relationship between bg and liver glycogen stores throughout the day?
glycogen stores rise after a meal in response to an increase in bg
between meals glycogen stores fall as glucose is released from liver glycogen to stabilize the bgc
overnight glycogen stores are mobilized to help maintain bgc
What are the α1-4 linkages in glycogen broken down by?
phosphorolysis
catalysed by glycogen phosphorylase
What happens during phosphorolysis?
glycogen phosphorylase removes single units from non-reducing ends of glycogen to form G-1-P
ATP isn’t involved
What is the role of phosphate in phosphorolysis?
the phosphate acts like water does in hydrolysis reactions
it can only break α-1,4 links up to within 4 glucose units from a branch point
What is the effect of transferase activity of the debranching enzyme?
it removes 3 residues from the branch and transfers them to the end of another chain in α-1,4-linkage
phosphorolysis
What is the role of the α-1,6-glucosidase activity of the debranching enzyme during phosphorolysis?
to break the α1-6 linkages of the single glucose unit left at the branch
to cleave the bond to form free glucose by hydrolysis
does not involve phosphate
the chain can then be broken down by phosphorylase until it meets the next branch point
What percentage of glucose mobilized from glycogen is ‘free’ glucose rather than glusoe-1-phosphate?
about 10%
Why can’t Glu-1-P be exported to the blood from muscle tissue?
bc muscle lacks Glucose-6-phosphatase
What is glycogen formed from?
UDP-glucose
What is the role of glycogen synthase in glycogenesis?
to add glucose units in α-1,4-linkage onto the glycogen chain using UDP-glucose
What si the role of UDP-glucose in glycogenesis?
it donates the first glucosyl residue and attaches it to the amac tyrosine in the glycogenin
What si the role of glycogenin in glycogenesis?
it extends the glucose chain by up to 7 additional residues from UDP-glucose via α-1,4-linkages
What are the limitations of glycogen synthase in glycogenesis?
can only do to a pre-existing chain of more than four glucosyl residues
can’t make branches
What is the role of branching enzyme?
to creates the branches of the glycogen molecule
Why is glycogen is a good E store?
bc it can be mobilised very rapidly
What are the enzymes phosphorylase and glycogen synthase regulated by?
hormones, stress and muscle contraction
What is a benefit of the branched structure of glycogen?
provides a large number of ends at which the polymer can be added to or broken down
Why is glycogen is a bad E store?
bc glucose is hydrophilic and associates with water increasing the overall weight and bulk
Where is glycogenolysis greatly accelerated?
In the liver in between meals or during extended fasting, when glucose is required for glycolysis by the brain and red blood cells
In muscle to fuel glycolysis during vigorous exercise
Why is glycogenesis activated?
to replenish liver glycogen stores after feeding
to replenish muscle stores when exercise ceases
What substances is glycogen phosphorylase in muscle allosterically regulated by?
AMP, ATP and glucose-6-phosphate
What is the role of AMP?
it activates phosphorylase
When is AMP present?
when ATP is depleted during muscle contraction
What do ATP and glucose-6-phosphate inhibit? WHat are they signs of?
phosphorylase
high E levels
What happens when ATP and glucose-6-phosphate are plentiful?
glycogen breakdown is inhibited
What is glycogen synthase allosterically activated by?
glucose-6-phosphate
What is glycogen metabolism regulated by?
covalent modification - the addition (and removal) of a phosphate group
What is the (de)phosphorylation of glycogen catalysed by?
phos - protein kinases, reversible modification
dephos - protein phosphatases
What does the cAMP cascade result in?
the phosphorylation of a hydroxyl group in a serine residue of glycogen phosphorylase, which promotes transition to the active state
What is the effect of phosphorylated enzymes being less sensitive to allosteric inhibitors?
even if cellular ATP levels and glucose-6-phosphate are high, phosphorylase will be activated
What is glycogen synthase converted into when is undergoes phosphorylation?
the ‘b’ (less active’) conformation
glycogen synthesis is inhibited
What is the difference between the ‘a’ and ‘b’ forms of enzymes?
A - active form of enzyme, is independent of allosteric regulators
B - a form of enzyme dependent on local allosteric controls
When is the phosphorylated form of metabolic enzymes the active or inactive form?
active - if it is involved in an catabolic reaction (breaking down)
inactive - if it is involved in an anabolic reaction (building up)
What is the difference between a-1,4 and a-1,6 linkages in a glycogen mlc?
4 - make straight linear connections
6 - makes branched non-linear connections
What are the intermediates of glycogenolysis in the muscle?
glycogen < G1P < G6P < pyruvate
pyruvate turns into lactate and co2
What are the intermediates of glycogenolysis in the liver?
glycogen < G1P < G6P (+ G6Pase) < glucose
What enzymes are used to break a-1,4 and 1-1,6 linkages?
1,4 - phosphorylase
1,6 - debranching enzyme
How does the synthesis of a glycogen molecule begin?
the synthesis of a new molecule of glycogen is carried out by glycogenin
it carries out the primary function
What does the primary function involve?
when glycogenin accepts the first glucosyl residue from UDP glucose
How does the branching enzyme work?
it transfers a block of 7 residues from a growing chain it creates a new branch with an α-1,6-linkage
What is the role of protein kinase?
to convert phosphorylase b into phosphorylase a
to convert glycogen synthase-b into glycogen synthase a
What is the role of protein phosphatase?
to convert phosphorylase a into phosphorylase b
to convert glycogen synthase a into glycogen synthase-b
