Metabolism Session 4 - Energy Storage Flashcards
Describe the major energy stores in a 70kg man
Type of Fuel
Weight (kg)
Energy Content (kJ)
Triacylglycerols
~ 15
~ 600,000
Glycogen
~ 0.4
~ 4,000
Muscle Protein
~ 6
~ 100,000
Where is glycogen stored, and in what quantities?
Stored in granules in
Liver – up to 100g
Skeletal muscle – up to 300g
Give the four reactions involved in glycogen synthesis, and the enzymes which catalyse them
1.Glucose + ATP –> Glucose 6-Phosphte + ADP (catalysed by hexokinase)
2.Glucose 6-Phosphate –> Glucose 1-Phosphate (catalysed by phosphoglucomutase)
3.Glucose 1-Phosphate + UTP + H2O –> UDP-Glucose + 2 Pi
4.Glycogen (n residues) + UDP-Glucose –> Glycogen (n+1 residues) + UDP
Glycogen synthase (a1,4 glycosidic bonds) and branching enzyme (a1,6 glycosidic bonds)
What else is UDP-glucose used in?
Interconversion of glucose to galactose via epimerase
Give the equation for the completed degradation of glycogen
Glycogen (n residues) + nPi 0.9n Glucose 6-Phosphate + 0.1n Glucose
Why can’t you completely degrade glycogen?
A small amount of primer is always preserved
Give first step of glycogen breakdown and enzyme used
1.Glycogen (n residues) + Pi –> Glucose 1-Phosphate + Glycogen (n-1 residues)
glycogen phosphorylase and debranching enzyme
What does glycogen phosphorylase do?
Attacks the a1,4 bonds on glycogen and releases glucose residues as G1P
What does debranching enzyme do?
Attacks glycogen at a1,6 branch points, releasing free glucose
Give second and third steps of glycogen degradation
- Glucose 1-Phosphate –> Glucose 6-Phosphate (catalysed by phosphoglucomutase)
- Glucose 6-phosphate + H2O –> Glucose + Pi (catalysed by glucose 6-phosphatase)
Why isn’t Glucose 6-phosphatase enzyme present in muscle cells?
Because G 6-P enters glycolysis in muscle cells directly, so it is not required to remove its phosphate. G 6-P converted to glucose in liver cells for distribution round body.
Name all the enzymes used in the degradation of glycogen
glycogen phosphorylase
debranching enzyme
phosphoglucomutase
glucose 6-phosphatase
How is glycogen metabolism regulated?
Glycogen synthase and glycogen phosphorylase allostericly controlled by high and low energy signals.
Glycogen synthase and glycogen phosphorylase also undergo covalent modification in response to changes in hormones. Glycogen synthase inhibited by phosphorylation and activated by de-phosphorylation, and vice versa for glycogen phosphorylase.
Compare the functions of liver and muscle glycogen
Liver Glycogen – Glucose store for all tissues of the body
Muscle Glycogen – Glucose 6-phosphate store, only used by muscle cells
What do glycogen storage diseases stem from?
An abnormality in one or other key enzymes
- Glycogen phosphorylase
- Phosphoglucomutase
- Glucose 6-phosphatase (liver)
What can glycogen storage diseases cause?
Increased/Decreased amounts of glycogen - Tissue damage if excessive storage - Fasting hypoglycaemia (low blood glucose) - Poor exercise tolerance Glycogen structure may be abnormal Usually liver and/or muscle are affected
Clinical severity depends on what enzyme/tissue is affected.
What does gluconeogenesis allow?
the production of glucose when carbohydrates are absent.
When does gluconeogenesis occur?
After 8-10 hours of fasting
Where is the main site of gluconeogenesis?
The liver
Give five possible substrates for gluconeogenesis
Pyruvate, lactate and glycerol can be converted to glucose
Essential and non-essential amino acids whose metabolism involves pyruvate or intermediates if the TCA cycle can be converted to glucose
Why can’t acetyl co-A be used for gluconeogenesis?
PDH is irreversible
Explain the steps used in gluconeogenesis
Reversible steps of glycolysis are used in gluconeogenesis and irreversible bypassed.
How are steps 1&3 of glycolysis bypassed in the process of gluconeogenesis? Outline reactions and give the enzymes that are used?
Steps 1 & 3 are by-passed by thermodynamically spontaneous reactions catalysed by phosphatases (glucose 6-phosphatase and fructose 1,6-bisphophatase):
Glucose 6-phosphate + H2O –> Glucose + Pi G = -ve
Fructose 1,6-phosphate + H2O –> Fructose 6-phosphate + Pi G = -ve
How is step 10 of glycolysis bypassed in the process of gluconeogenesis? Give reactions and enzymes used.
Step 10 is by-passed by two reactions driven by ATP and GTP hydrolysis and catalysed by pyruvate carboxylase and phosphoenolpyruvate caroxykinase (PEPCK) respectively:
Pyruvate + CO2 + ATP + H2O –> Oxaloacetate + ADP + Pi + 2 H+ G = -ve
Oxaloacetate + GTP + 2 H+ –> Phosphoenolpyruvate + GDP + CO2 G = -ve
What does reaction ten provide a link between? What does it enable?
The TCA cycle and gluconeogenesis. Enables the products of amino acid catabolism that are intermediates of the TCA cycle to be used to synthesise glucose.
What two enzymes are regulated in the process of gluconeogenesis?
PEPCK and Fructose 1,6-bisphosphonate.
How is PEPCK Kinase regulated in gluconeogenesis?
is increased by – Glucagon, Cortisol
is decreased by – Insulin
How is fructose 1,6 bisphosphonate activity regulated in process of gluconeogenesis?
is increased by – Glucagon
is decreased by – Insulin
How does gluconeogenesis contribute to hyperglycaemia in gluconeogenesis?
Low insulin/anti insulin ratio. Key enzymes in gluconeogenesis (PEPCK and Fructose 1,6-bisphosphonate) not inhibited, so continues unchecked.
Why are tags efficient energy stores?
Hydrophobic and stored in an anhydrous form. Highly reduced, so lots of energy.
