systems to cells Flashcards
diabetes
describe the make up of ATP
Adenine- two ring structure attached to ribose sugar.
adenine and ribose sugar are attached to adenosine. which is attached to tri (3) phosphate groups.
difference between hypoglycaemia and hyperglycaemia?
hypo- low blood glucose
hyper- high blood glucose
what is gluconeogenesis?
metabolic pathway that results in the generation of glucose from non carbohydrate substrate of lactate or amino acid-
reverses glycolysis.
insulin turns this off and glucagon turns this on.
explain the reaction involved in the breakdown and synthesis of glycogen
when blood sugars rise. insulin is secreted from pancreatic beta cells.
glucose is converted to glucose-6-phosphate by hexokinase. this is reversed by glucose-6- phosphatase.
Then it’s converted to glucose-1- phosphate by phosphoglucomutase. this is a reversible reaction by the same enzyme.
Then it is stored as glycogen by glycogen synthase. by protein phosphatase 1. when blood sugar drops glycogen is converted back to glucose-1-phosphate by glycogen phosphorylase. THIS REACTION IS IRREVERSIBLE!.
goes back through pathway until it is Brocken down into glucose.
regulated by turning on/ off the enzymes.
explain different ways enzymes are regulated (turned on/off) by kinase/ phosphatase system
-two main classes of kinase
phosphorylation- involves covalent addition of phosphate from ATP by kinases.
dephosphorylation- removal of phosphate by phophatases.
two main classes of kinase- those that phosphorylate tyrosine residues and serine/ threonine residues.
how glucagon degrades glycogen?
cAMP is a secondary messenger synthesised from ATP which activates protein kinase A (PKA).
PKA phosphorylates glycogen synthase (turning it off)
PKA phosphorylates glycogen phosphorylase (turning it on).
glycolysis is tuned off
glucagon causes phosphorylation of both enzymes
insulin causes dephosphorlyation of both enzymes
how insulin promotes glycogen synthesis
insulin switches on protein phosphatase 1 by AKT. which dephosphorylates glycogen phosphorylase, leading to turned on glycogen synthase. = glycogen
glycolysis is turned on
insulin causes dephospho rylation of both enzymes
what is the rate determining step?
the slowest step in a reaction, as the energy requirement is larger.
also seen as the irreversible steps eg glycogen synthase and glycogen phosphorylase.
what part of the pancreas secretes hormones
and what cells does the pancreas contain?
islets of langerhans
- a and b cells
-delta cells
translation of preproinsulin
-where is preproinsulin translated
-what and where does it move to to form proinsulin.
-where is insulin formed
-what enzymes cleave proinsulin in insulin
1) preproinsulin translated on ribosomes in cytosol: proporinsulin has signal peptide at the N terminus guiding into the ER.
2) the signal peptide is cleaved off in ER which results in proinsulin. folding only happens in the ER.
3) proinsulin held stable due to disulphide bonds forming.
4) proinsulin moved to Golgi and packaged into secretory vehicles.
only have biologically active insulin in nature secretory vehicles after c peptide is released.
5) proinsulin is cleaved into insulin and c-peptide by enzymes PC 1/3 and PC2.
what is regulated exocytosis?
release of controlled hormones from vesicles at a specific signal eg
release of insulin in response to glucose levels. and GLUT-4 taking up excess glucose by activation of AKT
how glucose gets from outside beta cell to inside beta cell?
GLUT-2 transporter. (low affinity/high KM)
the two glucose sensors in beta cells?
GLUT 2
glucokinase
what triggers insulin release in beta cells?
glucose phosphorylation in beta cells uses low affinity/ high KM enzyme glucokinase (same as hexokinase but only in beta cells)
-therefore converts glucose to glucose 6 phosphate results in glycolysis and the rise of ATP.
- as ATP increases, it closes ATP sensitive potassium channels. results in the depolarisation of cell membrane. = inside becomes more positive
depolarisation opens calcium channels allowing calcium influx
-triggering fusion of insulin containing secretory vesicles=
insulin exocytosis= release of insulin to glucose levels
meaning of a high KM?
enzyme is more active at a higher glucose concentration
structure and function of insulin receptor?
structure- a2b2 polypeptide
held together by. disulphide bonds. contains 2 alpha subunits at insulin binding site outside cell membrane.
contains 2 beta subunits inside membrane.
how does insulin exert its effect on target tissue?
-enzyme tyrosine kinase
-auto-phosphorylation
-signalling protein IRS-1
-protein SH2
-enzyme AKT
1) when insulin binds to alpha subunits they go through conformational change which activates intrinsic tyrosine kinase activity in betas subunits.
2) the activated beta subunits phosphorylate tyrosine residues on themselves called (AUTOPHOSPHORYLATION) enhancing kinase activity.
2) kinase can phosphorylate several intracellular signalling proteins such as (IRS-1).
3) IRS-1 are phosphorylated on tyrosine residues. these phosphorylated sites serve as docking points for proteins such as (SH2 domains). - bind phosphotyrosine residues in specificity pocket.
4) THIS ACTIVATES THE ENZYME ‘AKT’. which is essential for insulin signalling by phosphorylating target proteins.
how insulin stimulates glucose uptake in fat and muscle cells?
GLUT-4 transporter (muscle, heart and fat)
insulin present-
activated AKT by binding of insulin receptors traffics GLUT-4 to cell surface - to take us excess glucose.= regulated exocytosis.
no insulin- GLUT-4 is stored in specialised vehicles in cytoplasm of adipose and muscle cells.
2 functions of AKT enzyme in fat cells and liver?
fat cells-
activates GLUT-4 trafficking to the cell surface to take up excess glucose
liver-
phosphorylates and activates protein phosphatase 1 (which promotes glycogen storage by activated glycogen synthase- and turns off glycogen phosphorylase.
