8. carbohydrate metabolism 1 Flashcards
where are the main stores of glycogen?
skeletal muscle 400g (1-2% fresh weight)
liver 100g (10% fresh weight)
where does mobilisation of glucose from glycogen occur?
in liver and kidney cells
in the muscle it serves as reserve for ATP synthesis
why is glucose stored in glycogen?
glycogen polysaccarides reduces osmotic forces on a cell
glycogen structure
one reducing end
and a non reducing end on every branch for rapid mobilisation (enzymes)
branches: alpha 1-6 glycosidic bonds
alpha 1-4 glycosidic bonds between molecules
Which cytosolic enzymes are needed for glycogen degradation?
- Glycogen Phosphorylase
- Glycogen Debranching enzyme
- Phosphoglucomutase
what does glycogen phosphorylase do?
dimer
Cleaves α(1→4) bonds until 4 glycosyl units remain on a branch point
- Binds pyridoxal-5’-phosphate
- a limit dextrind (fragment cant break down)
allosteric Interactions & covalent modification
Inhibitors: ATP, G6P, Glucose
Activator: AMP
-Induces conformational change (reveals buried active site)
Glycogen Debranching Enzyme
bifunctional with separate active sites:
- acts as a α(1→4) transglycosylase (glycosyltransferase) moves trisaccharide units to non-reducing branch end for glycogen phosphorylase
- then hydrolytically removes the remaining glycosyl using amylo-α(1→6)-glucosidase activity
10% released as just glucose
what does the reducing end have
anomeric carbon C1 not linked to another glucose, free aldehyde group
non reducing does not have a free aldehyde group
Phosphoglucomutase
- Glycogen Phosphorylase converts the glycosyl units of glycogen to G1P
- then phosphorylation of the glucose molecule followed by a re-phosphorylation of the enzyme
- G6P can continue along the glycolytic pathway or the pentose phosphate pathway. It can be hydrolysed by glucose-6-phosphatase to glucose (bloodstream)
Glycogen synth: when might this happen?
G6P produced by gluconeogenesis may not be hydrolysed to glucose but may be converted to G1P for incorporation into glycogen
Describe glycogen synthesis (glycogenesis)
Glycogen synthase makes alpha(1-4) to extend existing chain but it cannot initiate formation
requires primer: glycogen fragment
if absent: protein glycogenin (catalyses) accepts glucose residues from UDP-glucose (usually attaches to glucose)
side chain OH of tyrosine site of attachment for initial glycosyl unit
branching enzymes transfers 5-8 residues from end of chain to alpha(1-6) resulting in a new non-reducing end and old non-reducing end to be elongated further
Regulation of Glycogenesis & Glycogenolysis
hormonal and allosteric
hormonal: insulin, glucagon and adrenaline
Hormones act through changes to phosphorylation state of enzymes
- cell surface receptor triggers intracellular events
- Adrenaline and glucagon act through a “second messenger” – cyclic AMP (cAMP)
Adrenaline acts on muscle and liver
Glucagon acts on liver
•Glycogen synthase
- Active form is dephosphorylated
- Level of inactivation proportional to phosphorylation level
Allosteric Regulation
- Permits rapid response
- Can override hormone-mediated covalent regulation
