L9: Regulation of Metabolic Pathways Flashcards
why does the body regulate carbohydrate metabolism
to maintain blood glucose conc in normal range
what is the normal range for blood glucose conc
3.6 - 5.8 mM/L
what 4 enzymes are regulated in carbohydrate metabolism
- Glycogen phosphorylase
- Hexokinase
- PFK-1
- Pyruvate kinase
how is glycogen phosphorylase activated
Allosteric regulation:
Occurs by phosphorylation on Serine 14
Occurs when GP binds to AMP in muscle cells
which amino acid residue is phosphorylated to activate glycogen phosphorylase
Serine 14
what hormones regulate the phosphorylation of GP at Ser 14
glucagon & adrenaline
what cells does glucagon act on
liver cells
what cells does adrenaline act on
skeletal muscle cells
how do glucagon & adrenaline cause the phosphorylation of GP
- both bind to receptors & activate signalling cascade
- cascade activates Protein Kinase A (PKA)
- results in phosphorylation & activation of GP causing glycogen breakdown (& produces G-1-P)
how is GP deactivated
- blood glucose conc returns to normal (3.6 -5.8 mM)
- glucagon & adrenaline no longer released
how is glycogen synthesis & catabolism reciprocally regulated
reciprocal regulation of their major regulatory enzymes: glycogen phosphorylase & glycogen synthase
what is a major activator of glycogen synthase
insulin
released when blood glucose conc is high, converts GS to an active non phosphorylated form
how many isoenzymes of HK are there
4 (I-IV)
where is HKIV exclusive to and what is it also known as
only found in liver cells
known as glucokinase
do HK I-III or HK IV have a higher Km for glucose (affinity for glucose)
HK I-III have a higher Km fr glucose than HK IV
HKIV Km for glucose
> 10 mM
what is HK I-III allosterically inhibited by
glucose-6-phosphate
is HKIV inhibited by high [G-6-P]
no
high conc of what activates GP in skeletal muscle
AMP
what happens to HKIV when blood glucose conc is low
- when blood glucose conc low (<5mM), HKIV binds a regulatory protein
- this sequesters HKIV in nucleus
- this causes glycolysis in the liver to be deactivated as HKIV in the wrong place (should be in nucleus)
(HK needed in glycolysis step 1)
what happens to HKIV when blood glucose conc rises (>6mM)
- glucose blocks regulatory protein binding
- this means HKIV can enter the cytosol & glycolysis can occur in the liver
what is the rate limiting step glycolysis
step 3 -PFK1
how is PFK1 regulated
allosterically & by hormone induced signalling
how is allosteric regulation of PFK1 activated
- activated by high conc of low energy indicators ([AMP] [ADP])
- also by high fructose 2,6-bisphosphate conc - a low energy indicator NB in liver
