Energy storage- glycogen and fat Flashcards
(19 cards)
what tissues have an absolute requirement for glucose?
Red blood cells
Neutrophils
Innermost cells of kidney medulla
Lens of the eye
What are the consequences of reduced blood glucose? give examples of the measurement
- 8 mmol/L = confusion
- 7 mmol/L = weakness, nausea
- 1 mmol/L = muscle cramps
- 6 mmol/L = Brain damage/Death
how is glycogen stored? What are the body’s main stores of glycogen?
Glycogen is stored as granules
Muscle glycogen (300g) - intra/intermyofibrillar glycogen, can only be used by muscle for contraction
Liver glycogen (100g) - can be used to replenish plasma glucose levels, stored in hepatocytes
Describe the structure of glycogen
Polymer - chains of glucose monomers
Branching organised like branches of a tree - originate from a dimer of protein GLYCOGENIN
straight - alpha 1-4 glycosidic bonds
Branched - alpha 1-6 glycosidic bonds (every 8-10 residues)
Outline the 4 stages of glycogenesis
1) glucose + ATP —> glucose-6-phosphate + ADP (hexokinase/glucokinase in liver)
2) glucose-6-phosphate —> glucose-1-phosphate (phosphogluco mutase)
3) glucose-1-phosphate + UTP —> UDP-glucose + PPi (G1P uridylyltransferase)
4) glycogen (n residues) + UDP-Glucose —> glycogen (n+1 residues) + UDP
(Glycogen synthase and branching enzyme)
Outline the process of glycogenolysis
1) glycogen (n residues) + Pi —> glucose-1-phosphate + glycogen (n-1 residues)
(Glucose phosphorylase or de-branching enzyme)
2) glucose-phosphate —> glucose-6-phosphate (phosphoglucomutase)
3) glucose-6-phosphate used for glycolysis I’m muscle for energy production and to maintain blood plasma concentration by the liver for use by other tissues
What enzyme effects the function of glycogen in the muscles and liver?
Glucose-6-phosphatase
Liver: G6P converted to Glucose and exported to blood
Muscle: lacks enzyme and therefore G6P enters glycolysis for energy production for muscle contraction
How is liver glycogen metabolism regulated?
Rate limiting enzymes
Synthesis= glycogen synthase
Degradation= glycogen phosphorylase
Glucagon, adrenaline = glycogen synthase = phosphorylation = decrease
glycogen phosphorylase =phosphorylation = increase
Insulin = glycogen synthase = de-phosphorylation= increase
glycogen phosphorylase = de-phosphorylation = decrease
In muscle glucagon = no effect, but AMP acts as allosteric activator of muscle glycogen phosphorylase BUT NOT OF LIVER FORM
What are glycogen storage diseases?
Inherited diseases - causing deficiency or dysfunction of enzymes of glycogen metabolism
Severity depends on enzyme/tissue affected
Liver and/or muscle can be affected
Excess glycogen can lead to tissue damage
Diminished glycogen stores can lead to hypoglycaemia and poor exercise tolerance
Give 2 examples of glycogen metabolism diseases
Von Gierke’s disease - G6Phosphatase deficiency
Mcardle disease - muscle glycogen phosphorylase deficiency
What is the role of gluconeogenesis?
Beyond 8 hours fasting liver glycogen stores will be depleted and a alternative source of glucose is required: gluconeogenesis
Occurs in the liver and lesser extent the kidney cortex
What are the 3 pre-cursors for gluconeogenesis?
1) Lactate From anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle)
2) Glycerol Released from adipose tissue
breakdown of triglycerides
3) Amino acids Mainly alanine
Why can’t we use acetyl-coA for a net synthesis of glucose?
Would have to feed to TCA cycle
2 carbons in - 2 lost in cycle so not net gain of carbon to produce glucose
What are the key enzymes in gluconeogenesis?
1) PEPCK - Phosphoenolpyruvate carboxykinase
2) fructose-1,6-bisphosphatase
3) glucose-6-phosphatase
What is the purpose of TAGs?
Energy intake in excess of requirements is converted into TAGs for storage
Hydrophobic- stored in anhydrous form
High efficient energy store
Utilised in prolonged exercise,starvation,pregnancy and stress
Storage and mobilisation is under hormonal control
Describe the overview of dietary TAG metabolism
1) fat broken down to fatty acids and glycerol by PANCREATIC LIPASE
2) TAG packaged into Chylomicron to pass through epithelial cells of intestine
3) TAG enters lymphatic system through lacteals and drains into the blood stream at the thoracic duct in the left subclavian vein
4) from here the TAGs can be utilised for fatty acid oxidation for energy or stored in adipose tissue
Describe the key features of liver lipogenesis
1) glucose enters glycolysis in the liver cell. Some goes of into the penthouse pathway to produce reducing power in the form of NADPH
2) pyruvate converted to AcetlycoA(2c) and oxaloacetate(4c) which condense together to form citrate which leaves the mitochondria and in the cytosol converted back
3) oxaloacetate —> malate —>pyruvate by malic enzyme provides kore NADPH
4) acetylcoA—>malonlylcoA via acetyl-coA
Inside fatty acid synthase complex, fatty acid chains are grown from NADPH sources ,2 carbons at a time by malonlyl coA (release of co2) to produce TAGs
How is lipogenesis controlled?
AcetylcoA carboxylase
Insulin (covalent de-phosphorylation) and citrate (allosteric) increase activity
Glucagon/adrenaline (covalent phosphorylation) & AMP (allosteric) decrease activity
How are fats released and mobilised?
Hormone sensitive lipase
Insulin - leads to dephosphorylation and inhibition of HSL
Glucagon and adrenaline - phosphorylation and activation of HSL
Once in blood glycerol travels to liver and utilised as carbon source in gluconeogenesis
Fatty acids travel complexed with albumin to muscle and other tissues for beta oxidation
