carbohydrate metabolism Flashcards
where does glycogen synthesis and degredation occur
liver and muscle
where does gluconeogenesis occur
liver and kidney.
why does the body aim to maintain blood glucose
- The brain uses glucose as a preferred energy source.
* So The concentration of glucose in the blood needs to be maintained in order that the brain can function normally
What happens if the glucose level drops below the critical level?
• Hypoglycaemia o Muscle weakness o Loss of coordination o Mental confusion o Sweating o Hypoglycaemic coma and death
what happens if the concentration of glucose increases too much?
• Hyperglycaemia
o Non enzymatic modification of proteins
Cataracts
o Hyperosmolar coma
what is glycogenesis
• Glycogen synthesis
Where does it take place and when does it take place
liver (100g glycogen stored) and skeletal muscle (300-400g) stored.
When blood glucose levels are high
What regulates glycogen synthesis
insulin which is produced by the pancreas in high glucose levels.
describe the glycogen molecule structure.
- Branched polymer of glucose
- Alpha 1-4 glycosidic bonds and alpha 1-6 glycosidic bonds.
- Very large and can be seen under microscope.
- Formed by a protein primer glycogenin, therefore in its absence, glycogen does not form.
why regulates the synthesis of glycogen levels
glycogen synthase and the branch points are introduced via the branching enzyme.
outline the steps in glycogen synthesis
- Convert glucose-6-phosphate to glucose-1-phosphate. This requires the enzyme phosphoglucomutase.
- Glucose-1-phosphate then reacted with UTP (uridine triphosphate) to form UDP-glucose.
- The UDP glucose reacts with glycogenin to form glycogenin with one glucose residue attached.
- Under the influence of glycogen synthase, more glucose residues are added to increase the length of the glucose chain attached to the glycogenin. The bonds formed are alpha 1-4 glycocidic bonds.
- The synthesis of the chain will continue until there are approx. 11 residues of glucose attached.
- The branching enzyme then takes 5 residues from the end of the glucose polymer and forms an alpha1-6 bond,introducing a branch point.
- Further glucose residues can be added to the ends of the 2 molecules.
why is glycogen
- Cannot store glucose as it is osmotically active so cannot be safely stored in great amounts in the cell.
- 400mM glucose is stored as 0.01µM glycogen – is less osmotically active
- The branched structure of glycogen means it can be rapidly mobilised
- Fat cannot be used as an energy source in the absence of oxygen.
- Fat cannot be converted in to glucose but glycogen can.
which enzyme forms the alpha 1-4 glycocidic bonds
• Glycogen synthase is the enzyme that forms the alpha 1-4 glycosidic bonds
which enzyme is responsible for the alpha 1-6 bonds
branching enzyme
what is glycogenolysis
Glycogen breakdown
when and where does glycogenolysis occur
- Occurs in the liver and muscle primarily, but can also occur in kidney
- Occurs when glucose levels are low
what is glycogenolysis stimulated by ?
• Stimulated by: glucagon, adrenalin, noradrenalin, and growth hormone.
outline the steps in glycogen break down
- The alpha 1-4 links are broken. this is achieved by the enzyme phosphorylase and results in the production of glucose-1-phospate.
- The glucose-1-phosphate is then converted to glucose-6-phosphate by the enzyme phosphoglucomutase.
3.
The phosphorylase will act until 4 residues are remaining. The debranching enzyme will then remove 3 of the residues and add them to the non-reducing end of the chain. This is called transferase activity. - The phosphorylase will continue to break down the alpha 1-4 links
- A second enzyme activity associated with the debranching enzyme will break down the last residue (alpha 1-6 glucosidase) forming the glucose.
- The glucose is then phosphorylated in muscle via hexokinase to form G-6-P which is then used in glycolysis.
- The phosphorylase continues to break down the chains, removing one residue at a time, producing glucose-1-phosphate.
- The G-1-P is converted to G-6-P via phosphoglucomutase, however if if this were in the liver, an enzyme called G-6-Phosphatase will convert the G-6-P into glucose which is then exported to the general circulation.
what is the function of glycogen phosphorylase
Phosphorylase breaks the alpha 1-4 bonds by adding an orthophosphate releasing glucose 1-phosphate
what are the two activities associated with debranching enzymes
1) transferase activity moves the last 3 glucose residues to the non-reducing end of an existing chain and 2) the glucosidase that breaks the 1-6 link releasing glucose.
what are the products of glycogenolysis
Glucose 1-phosphate
Glucose
what are the three enzyme activities required for glycogenolysis
– Phosphorylase breaks the a1-4 links
– Transferase moves 3 residues to an existing chain
– Debranching enzyme breaks a1-6
what is the function of Phosphoglucomutase
converts G1P to G6P
what does the fate of g-6-p depend on?
depends on whether it is in the liver or muscle.
• Liver – possesses the enzyme G-6-phosphatases which converts the G-6-P to glucose which is then exported. – occurs in the liver and kidneys but not skeletal muscle. If muscle the G-6-p will then be used in glycolysis.
what is glycogen phosphorylase regulated by?
- It is regulated by allosteric interactions that signal the energy state of the cell
- Also regulated by reversible phosphorylation regulated by hormones both in a positive and negative way such as insulin, glucagon, adrenalin and noradrenalin
- Regulation of glycogen phosphorylase differs in muscle and liver - due to function glycogen plays in the tissues.
what are the 2 isoforms of glycogen phosphorylase
active isoform- phosphorylase A, inactive isoform – phosphorylase b,
• The active isoform is phosphorylated
• Glycogen phosphorylase b (inactive) is converted to the active form by phosphorylase b kinase – which transfers a phosphate from an ATP to one serine residue on each phosphorylase subunit.
outline steps in the signal transduction cascade leading to the activation of phosphorylase a through the binding of adrenaline to its receptor
- This results in adenylate cyclase activation and the generation of cyclic AMP.
- Cyclic AMP will phosphorylate protein kinase A and this will form the active form of protein kinase A which will phosphorylate and activate phosphorylase kinase
- Phosphorylase kinase will activate phosphorylase A through phosphorylation.
- The activation of phosphorylase A leads to glycogen breakdown through the breaking of the alpha1-4 links and generation of g-1-p.
in addition to activating phosphorylase kinase, what is another function of protein kinase a
phosphorylates glycogen synthase - this leads to inactivation. This means, through the single receptor, there is both stimulation of breakdown and inhibition of syntheses.
how is glycogen phosphorylase controlled in the muscle
and in the liver
• In muscle glycogen phosphorylase b can be activated by 5´-AMP without being phosphorylated. The 5’-AMP forms when ATP is depleted
-• AMP is a good indicator of the energetic state of a cell, in muscles AMP IS GENERATED when the cell is actively contracting and therefore there is an increase in the requirement for substrates such as glucose
-• ATP binds to the same site as AMP and blocks activation. This means that when the energetic state of the cell is high and the requirement for glucose is low, the enzyme is inhibited.
• Glucose-6-phosphate also blocks 5´-AMP activation
in the liver, the activated phosphorylase a is inhibited by glucose – important – phosphorylase function in the liver is to generate glucose to be released into circulation- glucose levels are high the need for glycogen break down is zero
how can Phosphorylase also be regulated by calcium
calcium through the ability of calcium to regulate phosphorylase b kinase.
• Ca2+ ions activate phosphorylase b kinase
how do muscles mediate glyogenolysis during muscle contraction?
ca2+ levels in contracting muscles are elevated.
what stimulates ca2+ release in the liver
o in liver α-adrenergic activation stimulates Ca2+ release
what are the 2 receptors that regulate phosphorylase kinase ?
the most important is through the elevation of cAMP and the activation of PKA the other is calcium mediated through the alpha adrenergic/IP3 pathway
compare glycogen synthase and glycogen phosphorylase
gs - activated in times of plenty, gp - acctivated when blood glucose is low, gs -stimulated by insulin, gp- stimulated by glucagon, adrenalin and noradrenalin, gs- activated by ATP and G6P, gp-inactivated by ATP and G6P, gs-inactivated by phosphorylation (pka), gp- activated by phosphorylation (pkb), gs- activated by dephosphorylation ( protein phosphatase-1) gp- inactivated by dephosphorylation ( protein-phosphatase1)
what is glycogen synthesis regulated by?
glycogen synthase
what enzyme is responsible for the breakdown of glycogen
glycogen phosphorylase
when does the pentose pathway occur
occurs when glucose levels are high
what does the pentose pathway start with formation of and end with the formation with
Starts with the Formation of glucose-6-phosphate and ends with the formation of ribose 5 phosphate – involved in biosynthetic pathways leading to nucleotides and nucleic acid synthesis.
what is formed in the pentose pathway and why is it important
NADPH - an important molecule in the synthesis of fatty acids, sterols is produced also important in the formation of glutathione ( important in the protective mechanism of the cell from oxidative stress).
what is gluconeogenesis
Synthesis from non-carbohydrate sources such as triglycerides, lactate and amino acids.
where does gluconeogenesis occur?
Predominantly in the liver (60%) and the kidney (40%) and a small amount in the intestine.
when does gluconeogenesis occur?
When blood glucose levels are low – fasting, starvation
in gluconeogenesis describe how pyruvate is converted back to glucose.
- Pyruvate is converted to oxaloacetic acid by pyruvate carboxylase.
- oxaloacetic acid is converted to phosphoenol pyruvate by the enzyme phosphoenol pyruvate carboxykinase.
- a series of reversible steps which ends with the next step that needs to be reversed – activity of phosphofructokinase. This is carried out by fructose 1-6 bisphosphatase.
- the activity of hexokinase is reversed by the enzyme glucose-6-phosphatase.
where can noncarb sources feed into the gluconeogenesis pathway
- Level of oxaloacetic acid – the aas will be converted into oxaloacetic acid and then converted to glucose
- Level of pyruvate – other aas are converted to pyruvate. Also, the level where lactic acid is converted to pyruvate, which is then converted to oxaloacetic acid and then glucose.
Lipids- triglycerides which contain glycerol and fatty acids:
The glycerol can be fed into the point of glycolysis where the molecule fructose1-6-bisphsphate is split – dihydroxyacetone phosphate or the glycerolaldehde-3-phosphate level, which can be converted to glucose using fructose 1-6 bisphosphatase and glucose-6-phosphatase.
what is a limitation of gluconeogenesis
Pyruvate carboxylase which converts pyruvate to oxaloacetic acid is a mitochondrial enzyme.
Therefore, pyruvate synthesised in the cytosol has to be transported into the mitochondria where it undergoes conversion to oxaloacetic acid. The oxaloacetic acid is then converted into malate so that It can be transported back out of the mitochondria and into the cytosol
The malate is then converted to oxaloacetic acid. The enzyme phosphoenol pyruvate carboxykinase can then convert the oxaloacetic acid to phosphoenol pyruvate. This requires a pyruvate carrier.
what is glucuneogenesis regulated by and why
- The pathway is regulated by glucagon, which inhibits enzymes in the glycolytic pathway, so molecules are funneled into the gluconeogenesis pathway
- this is because it is trying to raise the blood glucose.
