Lecture 9 Flashcards
(24 cards)
Glucose toxicity
Need to keep it at [4-5mM] as it is very reactive in vivo. Reacts chemically with every protein in the body without needing an enzyme uncontrollably destroying protein function (glycation)
glycation indicators
Fasting for 8-12 hrs and taking blood test and/or measuring HbAlc to see how many Hb molecules are glycated.
Tolerant glucose disposal
return to basal layers
Intolerant glucose disposal
Normal fasting glucose but slow clearance, more exposure to increase [glucose] between meals
Diabetic glucose disposal
Fasting hyperglycaemia, constant exposure to high [glucose]
Tolerant but insulin resistant
Need to increase insulin secretion to remove glucose
Intolerant
Secreting more insulin but not enough to get over resistance. Constant hyperinsulinemia.
T2 Diabetes
B-cells exhausted unable to dynamically responds and maintain basal euglycaemia
Amylose
Linear, forms helices. Difficult for amylase to penetrate. Flatulence (beans, low GI food)
Amylopectin
Branched, easy hydrolysis/digestion
Glycemic Index
Describes post-prandial glucose response. Area under the test food curve / area under a reference curve (usually 50g). Expressed as %, GI of amylopectin foods (modern grains) >80. Test tube given will have 50g of digestible carbs. Sugary foods are fructose and low GI as body doesn’t respond to insulin, same does dairy.
Glucose disposal
In addition to the background transport facilitated by GLUT-1. Rapid removal of glucose from bloodstream. Important to do something with the glucose otherwise it exists cell.
Liver glucose disposal
GLUT-2. Initial filter as blood comes from hepatic portal vein. Insulin independent
Muscle glucose disposal
GLUT-4/ Very high capacity to get rid of glucose. Strongly dependent on insulin.
White adipose tissue glucose disposal
GLUT-4. Not a very active tissue but so much of it.
Phosphofructokinase
Rate limiting step of glycolysis. Not directly stimulated by insulin. Regulated allosterically by many things esp. AMP stimulated by low energy charge.
GLUT 2 used to take up glucose
Very high activity and very abundant [BGL] = [Liver glucose]
Glucokinase
Rapidly converts G to G6P. Not inhibited by buildup of G6P. High Km (10mM) for glucose, not saturated by high levels of liver glucose. So, [G6P] increases with [blood glucose]
G6P can stimulate inactive G5
Even phosphorylated G5. Glucose itself also stimulates the dephosphorylation of G5 involving kinases and phosphatases.
Glycogenesis in liver
the ‘push’ mechanism. Glycogenesis responds to BGLs without the need of insulin. Although insulin will stimulate glycogen synthase further.
Glycogenesis in muscle
[G6P] never get high enough to stimulate as. ‘pull’ method as insulin stimulates G5 and drags glucose to glycogen.
Glucokinase
Only works on glucose. Increases Km for glucose ~10mM. Not inhibited by G6P, only presents in liver, B cells. Responsive to [BGLs] changes.
Hexokinase
Works on any 6C sugar. Km for glucose ~0.1mM. Strongly inhibited by its product G6P. Present in all other tissues. If G6P is not used immediately, its build up and inhibits HK. Easily saturated with glucose..
Glycogenesis
In both liver and muscle , 2 ATPs required for the incorporation of a glucose into glycogen chain. G to G6P and UDP to UTP. Branching enzyme needed to introduce alpha 1-6 branch points and limit to the size of glycogen molecule (branches become too crowded even if they become progressively shorterm glycogen synthase may need to interact with glycogen to be fully active.
