carbohydrate metabolism Flashcards
what are the symptoms of hypo and hyperglycaemia?
HYPOGLYCAEMIA (too little glucose): β muscle weakness β loss of coordination βmental confusion β sweating β hypoglycaemic coma and death
HYPERGLYCAEMIA
(too much glucose):
β non-enzymatic modifications of proteins (cataracts, lipoproteins important in atherosclerosis, etc.)
βhyperosmolar coma
what happens when there is excess glucose in the body?
βglycogen synthesis
β pentose phosphate pathway
β fatty acid synthesis
what happens when there is a lack of glucose in the body?
βglycogen breakdown
β gluconeogenesis
what happens to glucose in the liver?
β Glucose from the bloodstream gets transported into the liver.
β using glucokinase, (ATP β ADP) gets phosphorylated to Glucose-6-Phosphate.
β It could get converted to Glycogen (and be converted back). This helps maintain glucose levels.
β It could be converted to Ribose-5-Phosphate (in the Pentose Phosphate Pathway)
β It could be converted to Pyruvate (and back). This is for aerobic/anaerobic respiration.
what are the steps in glycogen synthesis?
1β Glucose-6-Phosphate is converted to Glucose-1-Phosphate by Phosphoglucomutase.
β Glucose-1-Phosphate is then converted to UDP-Glucose via UDP-glucose-pyrophosphorylase (using UTP).
β The UDP-Glucose then combined with Glycogenin to initiate glycogen synthesis, as it acts as a primer required by Glycogen Synthase (GS) to attach additional glucose molecules.
β Glycogen Synthase facilitates the addition of additional glucose monomers via 1-4 glycosidic bonds)
how are branches in glycogen formed?
β every 11 glucose monomers that are added, some are transferred (by branching enzymes) to be in a branch via a 1-6 glycosidic bond.
why is glycogen used?
βglycogen cannot be stored (as it is osmotically active) - β400 mM glucose is stored as 0.01 ΞΌm glycogen (so 10 mM)
β fat canβt be mobilized as readily
βfat canβt be used as an energy source in the absence of oxygen
βfat canβt be converted in to glucose
what are the four enzymes needed to break down glycogen and what do they do?
βphosphorylase breaks the Ξ± 1-4 links
βtranslocase transports G-6-P to ER for further modification
β debranching enzyme - debranches (acts on 1-6 links) βphosphoglucomutase - converts G1P to G6P
what are the five enzymes needed to form glucose?
βphosphorylase βtranslocase βdebranching enzyme βphosphoglucomutase βglucose 6 phosphatase converts G6P to glucose (present in the liver and kidney, but not muscle)
how is glycogen broken down?
βThe way glycogen is broken down is the reverse of synthesis.
βThe enzyme important for breaking down glycogen will remove individual units until it eventually removes the whole branch.
βThe Ξ± 1-4 links are broken to remove the units individually, done by the enzyme Phosphorylase.
βThis gives G1P, which are then converted to G6P by Phosphoglucomutase.
how does glycogen phosphorylase work?
βkey enzyme in glycogenolysis and its activity forms G1P.
βlarge, multisubunit enzyme.
βMany Phosphorylase molecules are bound to each glycogen particle.
βThe G6P ultimately formed provides fuel for working muscles.
βIn the liver, the G6P is dephosphorylated (by G-6-Phosphatase) and secreted into the blood, maintaining the 5mM blood sugar concentration.
how is glycogen phosphorylase controlled?
β interchangeable active and inactive forms.
βThe inactive form is Phosphorylase B, and the active form is Phosphorylase A.
βPhosphorylase is an example of an βallostericβ enzyme; it is activated by phosphorylation, but modulated by other factors.
how is glycogen breakdown inhibited in the liver?
β In the liver, glycogen breakdown by Phosphorylase is inhibited by the presence of glucose, even after the enzyme has been activated to the a form by being phosphorylated.
how is phosphorylase b activated in muscle?
βIn muscle, Glycogen Phosphorylase b can also be activated without being phosphorylated.
β5Β΄-AMP (which forms when ATP is depleted) binds to another allosteric site, the nucleotide-binding site.
βATP will bind to the same site, blocking the activation.
βGlucose-6-phosphate also blocks 5Β΄-AMP activation.
what hormones control the regulation of glycogenolysis in the liver and in the muscle?
βDifferent hormones stimulate it in different places.
βin the liver, it is stimulated by Glucagon
β in the muscle, it is stimulated by Adrenaline (Cortisol is a weak stimulus of glycogenolysis, and Insulin inhibits it.)
describe the hormonal regulation of glycogenolysis
β1) Adenylate Cyclase is stimulated to make more Cyclic AMP.
β2) This activates Protein Kinase A.
β3)activates Phosphorylase Kinase
β4) activates Phosphorylase, turning it from Phosphorylase B to Phosphorylase A.
β5) removes glucose molecules from Glycogen as G1P.
(Activated Protein Kinase inhibits the activity of Glycogen Synthase, converting the active Glycogen Synthase A to the inactive form Gluycogen Synthase B)
How is Phosphorylase Kinase regulated?
βPhosphorylase Kinase is under dual regulation via two different receptor types.
βThe most important is through the elevation of cAMP and the activation of PKA.
βThe other is calcium-mediated through the alpha adrenergic/IP3 pathway.
how is glycogen synthesis and degradation reciprocally regulated?
βvia Glycogen Synthase and Glycogen Phosphorylase.
βGlycogen Synthase is activated in times of plenty glucose.
βGlycogen Phosphorylase is activated when glucose is in short supply.
what are Glycogen Synthase and Glycogen Phosphorylase activated and inhibited by?
GLYCOGEN SYNTHASE:
βactivated by ATP and G6P
βinactivated by phosphorylation (by Protein Kinase A)
β activated by dephosphorylation (by Protein Phosphatase-1)
GLYCOGEN PHOSPHORYLASE:
β inactivated by ATP and G6P
βactivated by phosphorylation (by Phosphorylase B Kinase)
βinactivated by dephosphorylation (by Protein Phosphatase-1)
what is the significance of the pentose phosphate pathway?
βThe pentose phosphate pathway is a metabolic pathway parallel to glycolysis.
βThe two most important products from this process are the ribose-5-phosphate sugar used to make DNA and RNA, and the NADPH molecules which help with building other molecules.
βThis pathway is special because no energy in the form of ATP is produced or used up in this pathway.
what is the significance of gluconeogenesis?
βThe body maintains the blood glucose because itβs the preferred fuel for the brain.
βWe use up more than our total body reserves can hold, so we constantly need to be making more.
what are the steps in gluconeogenesis?
1) Pyruvate (3C) is converted to Oxaloacetic Acid by Pyruvate Carboxylase.
2) Oxaloacetic Acid is then converted to Phosphoenol Pyruvate by Phosphoenol Pyruvate Carboxykinase.
3) Phosphoenol Pyruvate is then converted to the C3 molecule (GAP)
4) GAP is then converted to Fructose-1,6-bisphosphate
5) Fructose-1,6-bisphosphate is then converted to Glucose-6-Phosphate by Fructose Bisphosphatase.
6) Glucose-6-Phosphate is then converted to Glucose by Glucose-6-Phosphatase.
βSome amino acids can also be converted back to glucose. These are called the Gluconeogenic amino acids.
βThey can be fed in at different parts of the process.
β(Note: Glucagon inhibits Phosphofructokinase and Pyruvate Kinase, ensuring that the two pathways donβt happen simultaneously)
how does pyruvate get converted to oxaloacetate in the liver?
1) Pyruvate is brought into the mitochondria (in the liver) via a Pyruvate carrier.
2) Pyruvate is converted to Oxaloacetate by Pyruvate Carboxylase.
3) To leave the liver, the Oxaloacetate is converted to Malate.
4) The Malate is then brought out of the mitochondria.
5) Now outside, it is converted back to Oxaloacetate and then the process continues.
what are the most important substrates in gluconeogenesis?
βThe most important substrates for Gluconeogenesis are the amino acid Alanine, Lactate and Glycerol.
