How often does the body require food intake?
Our bodies have evolved to cope with intermittent food intake
How is excess food stored in our bodies?
Excess food is stored as glycogen
Compared to our needs, how much food do we intake?
Intake > needs
we take in excess food
Where is the long term glycogen store?
Fat in adipose tissues
Where is the short term supply of glycogen stored?
Liver / Muscle
What is gluconeogenesis?
Formation of glucose from precursors that aren’t carbohydrates
e.g. amino acids + glycerol -> gucose
What happens when food source is low or there’s an increase in demand ?
Stored energy is mobilised to glucose or fatty acids
Which hormone stimuates gluconeogenesis?
Glucagon
Which processes make up the metabolic pathway of carbohydrates?
- Glycolysis (glucose -> pyruvate)
- Pyruvate dehydrogenated (pyruvate -> acetyl coa)
- Citric acid cycle
- oxidative phosphorylation
What is hyperglycaemia?
Critically high blood glucose levels
What does the body do when glucose levels get too high?
Synthesise glycogen and fatty acids via the Pentose 5 pathway
What is hypoglycaemia?
Critically low blood glucose levels
What occurs when glucose levels get very low?
Glycogen degradation (gluconeogenesis)
What is the normal critical blood glucose level?
2.5mM
Outline the stages of the Pentose 5 Pathway
- Glucose is phosphorylated to G6P (glucose-6-
phosphate) - G6P converted to Glucose-1-phosphate by the enzyme
phosphoglucomutase - UDP added to glucose molecule forming UDP-Glucose
by UDP-glucosephosphorylase - Glycogenin enzyme reacts with UDP-Glucose to
catalyse the addition of the first glucose molecule - Glycogen synthase adds glucose residues in a 1-4
configuration until am 11 residue length is formed - stimulates branching enzyme to add a 1-6 branch
What is the role of the glycogenin enzyme?
Acts as a primer to polymerise the first few glucose residues
- without glycogenin glycogen wouldn’t form
Explain why glycogen is a better storage molecule than glucose
Glucose is very osmotically active so large concentrations cannot be stored
Glycogen is more compact so can be stored
(400mM of glucose stored as 0.01um glycogen)
What are the products of glycogen degradation?
Glucose-1-phosphate and glucose
Explain why glycogen is a better energy store than fat
Glycogen is hevaliy branched so potential residues can be released very quickly
Fat can’t be mobilised easily
Fat can only be used as an energy store in the presence of O2
Fat can’t be converted back to glucose
What is the benefit of adding UDP to glucose during the Pentose 5 Pathway?
Makes the glucose more readily reactive
Which enzyme synthesises glycogen?
Glycogen synthase
Describe the structural arrangement of Glycogen
- Branched molecule
- LInear glucose residues
- ɒ 1-4 links and ɒ 1-6 branched molecules
- glycogenin enzyme present
Outline the process of degradation of glycogen
- ɒ 1-4 links degraded by phosphorylase
=> forms Glucose-1-Phosphate - Glucose-1-phosphate converted to G6P by
phosphoglucomutase - Debranching transferase takes all, but last residue on
branch and adds it to the 1-4 chain - Debranching glucosidase removes 1-6 branching link
- Directly generates glucose
What happens to the glucose produced from glycogen degradation?
In muscle, glucose phosphorylated and reused or phosphorylated to Glucose-1-phosphate
What are the 4 enzymes required to break down glycogen?
- Phosphorylase
- Translocase
- Debranching enzyme
- Phosphoglucomutase
Where is the G6P produced in degradation used?
In muscles used in either the glycolytic pathway or citric acid cycle
- provides fuel for working muscles
Describe the structure of glycogen phosphorylase enzyme
Large and multisubunit enzyme
- many phosphorylases bind to each glycogen molecule
Where is glucose-6-phosphatase enzyme found in the body?
Liver and KIdney (not in muscle)
In the liver, what happens to glucose-6-phosphate?
G6P is phosphorylated by G6phosphatase and secreted into the blood, maintaining the 5mmolL-1 blood sugar
What is the role of glycogen phosphorylase?
Key enzyme in glycogenolysis in converting glycogen to glucose
Which enzyme is required for glucose formation from glycogen?
Glucose-6-phosphatase
How is phosphorylase enzyme an example of an allosteric enzyme?
Allosteric site away from active site - induce shape changes
What is the role of phosphorylase b kinase?
Converts inactive Glycogen phosphorylase b to the active a form
In muscles how else can glycogen phosphorylase b kinase be activated?
Activated by 5’ AMP without being phosphorylated
How is glycogenolysis so rapid?
Many phosphorylases bind to glycogen molecules for max activity
What regulates the activation of glycogen phosphorylase b kinase activation in muscles?
ATP and G6P are both competitive inhibitors
How does phosphorylase b kinase work?
Transfers a phosphate from an ATP to one serine residue on each phosphorylase subunit
When is the Pentose 5 Pathway activated?
Under high levels of G6P
What activates the phosphorylase b kinase enzyme?
calcium ions
How is maximum activity achieved in muscle cells?
With both calcium ions release and phosphorylation
Summarise how glycogen synthase is regulated
Activated by ATP and G6P
Activated by dephosphorylation by protein phosphatase-1
Inactivated by phosphorylation (protein kinase a)
How is phosphorylase b kinase activity regulated in the liver?
Inhibited by glucose as glycogen breakdown is inhibited by glucose presence even after the enzyme has been converted to its active form
What are the two receptor types regulating phosphorylase kinase?
- cAMP elevation and PKA activation
- Calcium mediated by ɒ adrenergic/IP3 pathway
When is 5’ AMP formed?
When ATP is depleted
In the liver what activates the release of calcium ions?
ɒ adrenergic receptors activation stimulates the release of calcium ions
How is glycogen phosphorylase/ degradtion regulated?
Inactivated by ATP and G6P
Inactivated by dephosphorylation by protein phosphatase-1
Activated by phosphorylation of phosporylase b kinase