Regulation of carb metabolism

Question 1

what is glycolysis

Answer 1

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)

Question 2

what is the glycolytic pathway

Answer 2

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

Question 3

what is gluconeogenesis

Answer 3

de novo glucose synthesis from non-carb precursors eg lactate from glycolysis, AAs from protein breakdown, glycerol (not FAs) from fat metabolism

Question 4

where does gluconeogenesis occur

Answer 4

liver (and kidney)

Question 5

what does gluconeogenesis do

Answer 5

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

Question 6

requirements for gluconeogenesis

Answer 6

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

Question 7

what is the urea cycle

Answer 7

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

Question 8

what is the. equation for the urea cycle

Answer 8

nh3+co2+2h2o+3ATP+aspartate= urea+fumarate+2ADP +AMP+2Pi +PPi
fumarate converted to oxaloacetate in cytoplasm generating a substrate for gluconeogenesis

Question 9

what is the gluconeogenic pathway

Answer 9

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

Question 10

what are the checkpoints in gluconeogenesis

Answer 10

glycolysis (glucose broken down, produce ATP, to pyruvate)
gluconeogenesis (oxalacetate to form glucose using 6 ATP per glucose)
reciprocally regulated

Question 11

how is glycolysis regulated

Answer 11

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)

Question 12

how is PFK-1 regulated by H+ ions

Answer 12

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)

Question 13

how is PFK-1 regulated by nutrients

Answer 13

subject to allosteric regulation by F6P, F2,6BP and citrate

Question 14

how is PFK-1 regulated by F6P

Answer 14

Activates
sign of high glucose entry or glycogen breakdown
stimulate glycolysis to utilisation for energy production or fat synthesis

Question 15

how is PFK-1 regulated by F2,6BP

Answer 15

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

Question 16

how is PFK-1 regulated by citrate

Answer 16

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

Question 17

what is an extra level of control of glycolysis

Answer 17

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

Question 18

what is fructose 2,6 Bisphosphate

Answer 18

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

Question 19

What is glycolysis inhibited by

Answer 19

presence of sufficient energy/ATP
FA oxidation indicting need for glucose sparing
H+ ions (lactate)

Question 20

what is glycolysis activated by

Answer 20

low levels of energy (AMP)

lots of glucose or its metabolites

Question 21

how does glycolysis vary between liver and muscle

Answer 21

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

Question 22

Why is extra control of F2,6BP required in the liver

Answer 22

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)

Question 23

how is gluconeogenesis activated

Answer 23

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

Question 24

how is gluconeogenesis controlled hormonally

Answer 24

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