Energy Storage Flashcards
Glucose is the preferred fuel
Some tissues have an absolute requirement for glucose as an energy source
Red blood cells - dont have a M
Neutrophils - main objective is elimination of ROS, dont have time for glycolysis
Innermost cells of kidney medulla - OxP is limited so rely on glucose
Lens of the eye - “
If plasma glucose falls, hypoglycaemia ensues e.g. diabetic patients
Stable blood glucose level absolutely essential for normal brain function.
Past 0.6 moles/L GLUT1 cant transport glucose into the brain - therefor brain damage may follow
To enable blood glucose to be kept at required levels, a store of glucose is required…GLYCOGEN
Glycogen is stored as granules
Muscle glycogen - Distinction between intra- (Intra) and intermyofibrillar (Inter) glycogen.
Glycogen storage granules in hepatocyte.
Glycogen structure
Glycogen is a polymer consisting of chains of glucose residues
Chains are organized like the branches of a tree originating from a dimer of the protein glycogenin
(acts as a primer at core of glycogen structure).
Glucose residues linked by
Glycogenesis
Glycogen synthesis:
Glucose converted to glucose-6P by hexokinsase + ATP
Glucose-6P is then converted to Glucose-1P by phosphoglucomutase
Glucose-1P combined with UTP and water forms UDP-glucose and PPi
UDP-glucose is then added to existing glycogen residues on the linear or branching chain
Glycogenolysis
Glycogen phosphorylase or a debranching enzyme breaks down glycogen(n residues) to glucose-1-P and Glycogen(n-1 residues)
The glucose-1-P is converted to glucose-6P and is either released by the liver into the blood for use by other tissues or its used up by muscles for energy production
Glycogen stores serve different functions in liver and muscle
G6P converted to glucose and exported to blood. Liver glycogen is a buffer of blood glucose level
Muscle lacks the enzyme Glucose-6-phosphatase. G6P enters glycolysis for energy production
Regulation of liver glycogen metabolism
Insulin and glucagon always oppose each other
Insulin inhibits glycogen mobilisation/ breakdown and stimulates glycogen synthesis
Glucagon/adrenaline vice versa
Muscle glycogen stores differ in that Glucagon has no effect.
Also AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of enzyme
Glycogen storage diseases
Inborn errors of metabolism (inherited diseases)
Arise from deficiency or dysfunction of enzymes of glycogen metabolism
12 distinct types. Incidence varies ~1 in 20,000 – ~1 in 100,000. Severity depends on enzyme/tissue affected
Liver and /or muscle can be affected
Excess glycogen storage can lead to tissue damage
Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance
Examples: von Gierke’s disease - glucose 6-phosphatase deficiency
McArdle disease - muscle glycogen phosphorylase deficiency
Gluconeogenesis - the production of new glucose
Beyond ~ 8 hours of fasting, liver glycogen stores start to deplete and an alternative source of glucose is required: Gluconeogenesis
Occurs in Liver and to lesser extent in Kidney cortex
Three major precursors:
Lactate from anaerobic glycolysis in exercising muscle and RBC
Glycerol released from adipose tissue
Tissue BD of TGs
The AA is mainly alanine
regulation of gluconeogenesis
2 key enzymes regulated by hormones in response to starving fasting, prolonged excercise and stress -
insulin inhibits gluconeogenesis (therefore inhibiting the 2 enzymes) and vice versa with glucagon (and cortisol)
Lipid storage
Energy intake in excess of requirements is converted to Triacylglycerol (TAG ) for storage
TAGs are hydrophobic and therefore stored in an anhydrous form in specialised tissue – adipose tissue
Highly efficient energy store. Energy content per gram twice that of carbohydrate or protein
Utilised in prolonged exercise, stress, starvation, during pregnancy
The storage & mobilisation of TAGs is under hormonal control
Adipocytes
Contain Large lipid droplets (mainly TAG and cholesterol ester)
Cytoplasm and organelles pushed to edge.
Typical adipocyte ~0.1mm in diameter.
Cells expand as more fat added
Average adult ~30 billion fat cells weighing ~15 kg.
Can increase in size about fourfold on weight gain before dividing and increasing total number of fat cells
When obese person loses weight, in the period of time after, its quite easy to put that weight on, as adipocytes are still present to store fat
Overview of dietary TGs metabolism:
Ingest fat into GI tract - in SI fat is acted upon by pancreatic lipase to break fat down to FA and glycerol
Both are absorbed into epithelial cells, where these are reconstituted to form TGs, and then these are encorporated into a lipoprotein particle, called a chylomicrons (responsible for transport of dietary fat.
From here they drain into the lymphatic system (unusual as most nutrients from GI tract go into our blood), and will remain in lymphatic system until it drains into circulatory system.
First time this TG (dietary fat from chylomicrons) enter blood vessels is in the left subclavian vein
From here the TGs they either head to the adipose tissue where they are stored as TGs, or they can be utilised by tissues for energy
Fats are mobilised in adipose tissue by a hormone called by hormone sensitive lipase (regulated by insulin (-vely) glucagon and adrenaline (+vely)
FA synthesis - lipogenesis
Mainly in liver. Dietary glucose as major source of carbon.
Glucose
Comparison of FA synthesis and ß oxidation
FA oxidation: Cycle of reactions that remove C2 C2 atoms removed acetyl CoA Produces acetyl CoA Occurs in mitochondria Separate enzymes Oxidative - produces NADH and FAD2H Requires small amount of ATP to activate the fatty acid Intermediates are linked to COA Regulated indirectly by availability of FA in mitochondria Glucagon and adrenaline stimulate Insulin inhibits
FA synthesis: Cycle of reactions that add C2 C2 atoms added as malonyl CoA Consumes acetyl CoA Occurs in cytoplasm Multi enzyme complex Reductive - requires NADPH Requires large amount of ATP to drive process Intermediates are liked to FA synthesis by carrier proteins Regulated directly by activity of Acetyl CoA carboxylate Glucagon and adrenaline inhibit Insulin stimulates