Regulation of carb metabolism Flashcards
what is glycolysis
metabolise glucose to produce energy from ATP via SLP, G3P for lipid synthesis, pyruvate for AcCoA for TCA/FA/cholesterol synthesis and AAs
reg by glucose transport into cell, PFK-1 and PK (in liver)
what is the glycolytic pathway
glucose-(ATP>ADP, Hk)-G6P-F6P-(ATP>ATP, PFK-1)-F1,6BP-Gly3P-1,3DPG-3PG-2PG-PEP-(ADP>ATP, Pk)-Pyruvate-TCA/Lactate
() irreversible steps that differ from gluconeogenesis
what is gluconeogenesis
de novo glucose synthesis from non-carb precursors eg lactate from glycolysis, AAs from protein breakdown, glycerol (not FAs) from fat metabolism
where does gluconeogenesis occur
liver (and kidney)
what does gluconeogenesis do
maintains blood glucose during fasting, starvation or when glycogen reserves are depleted too preserve brain
not a simple reversal of glycolysis, unique enzymes to overcome energetically unfavourable reaction and introduce points of control
requirements for gluconeogenesis
source of carbon (carbon skeletons) for forming glucose provided by lactate, AA or glycerol from TGs by lipolysis in adipose tissues
source of energy for biosynthesis provided by FA metabolism released by lipolysis in adipose tissue
what is the urea cycle
inc rate of gluocneogenesis coupled with inc rate of urea synthesis
AAs must be transaminated to lose ammonia
ammonia toxic to cells eliminated as urea via kidneys
what is the. equation for the urea cycle
nh3+co2+2h2o+3ATP+aspartate= urea+fumarate+2ADP +AMP+2Pi +PPi
fumarate converted to oxaloacetate in cytoplasm generating a substrate for gluconeogenesis
what is the gluconeogenic pathway
pyruvate to glucose
F1,6P to F6P via F1,6bisphosphatase
G6P to glucose via G6Pase (all enzymes mentioned irreversible steps)
pyruvate via pyruvate carboxylase to oxaloacetate via phosphoenolpyruvate to carboxylase to PEP back to pyruvate
what are the checkpoints in gluconeogenesis
glycolysis (glucose broken down, produce ATP, to pyruvate)
gluconeogenesis (oxalacetate to form glucose using 6 ATP per glucose)
reciprocally regulated
how is glycolysis regulated
PFK-1 subject to energy dependant allosteric reg by ATP, AMP, H+ ATP inhibits (stops glucose used, coordinates glycolysis with glycogen breakdown via phosphorylase) AMP activates (inc glycolysis and energy production, coordinates glycolysis)
how is PFK-1 regulated by H+ ions
H+ inc during anoxia or anaerobic muscle contraction (lactic acid production)
inhibit glycolysis to stop cellar pH falling and damaging cell
heart can be overcome by high AMP = cellular damage and chest pain (MI and angina)
how is PFK-1 regulated by nutrients
subject to allosteric regulation by F6P, F2,6BP and citrate
how is PFK-1 regulated by F6P
Activates
sign of high glucose entry or glycogen breakdown
stimulate glycolysis to utilisation for energy production or fat synthesis
how is PFK-1 regulated by F2,6BP
signals high rates off glucose entry to glycogen breakdown and leads to activation
most potent allosteric activator known
stimulates glycolysis for utilisation for energy production and fat synthesis
how is PFK-1 regulated by citrate
inhibits
signals TCA cycle overload, more acetyl CoA then can be oxidised or fatty acid oxidation and the need to conserve glucose by inhibition of glycolysis
what is an extra level of control of glycolysis
F6P to F2,6BP via PFK-2 and back via F2,6BPase
PFK-1, PFK-2, F2,6BPase all cells and F1,6BPase liver and kidney
what is fructose 2,6 Bisphosphate
synthesised from F6P via PFK-2
Most potent allosteric activator of PFK-1
potent inhibitor of F1,6BP
not involved in metabolic pathways, acts only to reinforce allosteric control on PFK-1
What is glycolysis inhibited by
presence of sufficient energy/ATP
FA oxidation indicting need for glucose sparing
H+ ions (lactate)
what is glycolysis activated by
low levels of energy (AMP)
lots of glucose or its metabolites
how does glycolysis vary between liver and muscle
muscle uses glucose and glycogen by inc F2,6BP stimulating glycolysis
liver uses glucose from gluconeogenesis and glycogen to maintain blood glucose so glycolysis is inhibited
Why is extra control of F2,6BP required in the liver
have to control glycolysis via PFK-1 but also the reverse reaction of gluconeogenesis at F1,6BP to allow reciprocal control
in liver PFK-2 and F2,6BP are single tandem enzyme with 2 active sites so phos stimulates F2,6BP and inhibits PFK-2
PFK-1 and F1,6BP controlled by level of F2,6BP affected by hormones (glucagon)
how is gluconeogenesis activated
inc FA ox leads to inc in AcCoA (activate P carboxylase and inhibit P DH) to activate
inc glucagon dec F2,6BP reduce PFK-1 activity (inhibit glycolysis) and inc F1,6BP to activate
how is gluconeogenesis controlled hormonally
stimulated in short term by glucagon and adrenaline by protein phos or mobilising FAs and prod AcCoA
long term stimulation occurs via enzymes induction by glucagon, glucocorticoids and thyroid hormones
inhibited by insulin (dephos) and suppression of lipolysis and gluconeogenic enzymes
