L12: glucose/lipid/protein metabolism Flashcards
What is metabolism?
Energy provision, storage and use
Where does energy come from?
Diet - carbs, lipids, proteins (a.a.s)
How is energy stored in our body?
Carbs stored as glycogen
Fats stored as triglycerides
What is energy most stored as?
Fats because fats are more energy dense
Why are carb stores needed?
Main source of energy in the short term
What organs are involved in fuel metabolism?
Pancreas is a regulator (it secretes hormones)
Liver, muscle and adipose tissue are all effectors
What is glycogen?
- storage polymer of glucose
- contained in liver and muscle - mainly muscle due to high energy demand
- provides 40-80% plasma glucose during 24hr fast
- insoluble molecule so does not affect osmosis of cells unlike glucose
Structure of glycogen
Highly branched polymer of glucose with both alpha1,4 and alpha1,6 glycosidic linkages
1,6 bonds cause branching
Many branches (around 1 every 10residues) allows more rapid release of glucose by faster breakdown of glycogen (greater SA)
(Image at 7:30)
How is glycogen made?
Made in glycogen granules
Enzyme - glycogenin allows the first few glucose molecules (at least 3) to link together in the process of forming glycogen (priming molecule)
Once 3 glucose molecules are linked by glycogenin, another enzyme called glycogen synthase adds extra glucose molecules
Glucose into glycogen (explanation)
- Glucose is converted into glucose-6-phosphate by the addition of a phosphate. Catalysed by glucokinase in the liver or hexokinase in the muscle.
- Phosphate on C6 moves to C1 by phosphoglucomutase to form glucose-1-phosphate
- Glucose-1-phosphate can be converted to glucose via glycogen synthase
Glucose pathways flow chart
Minute 10
Glycogen into glucose (explanation)
A glycogen molecule with n number of glucose molecules will release one glucose-1-phosphate molecule, leaving us with a glycogen molecule with one less glucose, n-1.
Regulated by glycogen phosphorylase
How is glycogen synthase regulated by hormones?
Positive activation by high levels of glucose due to high glucose causing high insulin levels. So insulin promotes glucose into glycogen.
Adrenaline and muscle contraction inhibit glycogen synthase, preventing G1P into glycogen.
How is glycogen phosphorylase regulated by hormones?
Adrenaline, glucagon and muscle contraction stimulate glycogen to glucose.
How do the uses of glucose differ in the liver and in the muscle?
Muscle has a high storage concentration of glycogen verse the liver
The liver is an organ which when it generates glucose, it releases it into circulation, to supply us with glucose in between food/during fasting
Muscle will use the energy generated from glucose metabolism for contraction
Difference between the release of glucose in muscle and liver
Glycogen will release a glucose molecule under the activity of glycogen phosphorylase to form G1P.
G1P is metabolised to G6P by phosphoglucomutase
G6P is trapped within the cell. Can be used to generate energy by entering the glycolysis cycle (predominant in the muscle)
If G6P is metabolised by removing the phosphate to generate glucose via glucose 6 phosphatase, then glucose can move out of a tissue if there are transporter molecules on its surface of the cell (predominant in liver)
Effects of muscle contraction on glucose levels
Muscle contraction enables the generation of glucose:
- when a muscle contracts calcium ions are released from SR
- the increase in cytoplasmic calcium ions causes a conformational change in Phosphorylase B kinase which adds a phosphate group to phosphorylase B (inactive) to form phosphorylase A phosphatase (active)
- phosphorylase A enables the activity of glycogen breakdown into G1P by enabling glycogen phosphorylase to be active
- allows glycolysis causing ATP and thus muscle contraction
Effects of adrenaline on glucose levels
(Flow diagram at 23:10)
Key points
- adrenaline has the combined effects of inhibiting glycogen synthesis and increasing glycogen breakdown to release glucose for the fight or flight response
- adrenaline actives protein kinase A
- protein kinase A phosphorylase phosphorylase kinase to activate it, which activates glycogen phosphorylase b into a
- at the same time adrenaline also inhibits glycogen synthase: protein kinase A inactivates glycogen synthase a into b by phosphorylating it
Why does adrenaline need the dual role?
Important to prevent the continual recycling of glucose
If adrenaline did not have this role of inhibition of glycogen synthase, then the glucose produced for the fight or flight response would just be converted back into glycogen
What are lipids?
- a dense source of energy
- insoluble in water
- fatty acids can have detergent-like properties
Main store of fats
Lipid = fatty acid and glycerol
Fatty acids are slightly soluble in water - bind to plasma proteins, depends on pH,
Fatty acids are often stored as Triacylglycerol (TAG) = 3 fatty acids linked to a glycerol
These are completely insoluble in water
Lipoproteins will make them more soluble
Where are lipoproteins synthesised
- intestine - areas where fats are absorbed. Produces a chylomicron (CM)
- liver - will produce a VLDL (very low density lipoprotein)
Different lipoproteins
Chylomicron (CM) is produced within intestine to transport our dietary uptake of fat into the body.
VLDL is a primary lipoprotein that leaves the liver.
Main difference between VLDL and other lipoproteins like IDL,LDLHDL, is the concentration of fat and cholesterol within them. VLDL will have higher conc of triglycerides, which drops down through the IDL,LDL,HDL, leaving more cholesteryl esters
CM has a major lipid of TG
On the surface of these vesicles are lipoproteins which are apoB (mainly)
Summary table at min 5
Major facts about chylomicron
- synthesised in the gut
- derived from dietary fatty acids
- fatty acid predominantly as core triacylglycerol
- comprise apolipoprotein B48 scaffolding surrounding lipid
- episodic, post-prandial flux
