gluconeogenesis

Question 1

gluconeogenesis

Answer 1

metabolic pathway in which a precursor is converted to glucose

Question 2

possible precursors to gluconeogenesis

Answer 2

pyruvate, lactate, glycerol (triglycerides), AAs (alanine), TCA cycle intermediates

Question 3

what cannot make glucose?

Answer 3

acetyl-CoA

Question 4

what relies on glucose as primary source of energy so its important to keep glucose levels constant?

Answer 4

brain, nervous system, red blood cells

Question 5

what is the main site of gluconeogenesis?

Answer 5

liver

Question 6

glycerol

Answer 6

supplied by adipose tissue
30% of fasting glucose from glycerol
glycerol-> glycerol 3-phosphate -> dihydroxyacetone phosphate (DHAP)
enzymes: glycerol kinase and glycerol 3-phosphate dehydrogenase
uses ATP and NAD+

Question 7

alanine

Answer 7

supplies by muscles and is the main AA released during fasting
alanine-> pyruvate
(aketoglutarate-> L-glutamate)
enzyme: alanine amino transferase
the alanine cycle exchanges alanine and glucose between skeletal muscle and liver

Question 8

lactate

Answer 8

supplied by red blood cells and skeletal muscle
lactate-> pyruvate
enzyme: lactate dehydrogenase
uses NAD+

Question 9

the cori cycle

Answer 9

lactate is produced in the muscles by homolactic fermentation. lactate is released into circulation and taken up by the liver where it is used to resynthesize glucose (using liver ATP), which is returned to the muscle (for glycogen storage or energy production)

Question 10

1st bypass step- synthesis of oxaloacetate from pyruvate

Answer 10

enzyme: pyruvate carboxylase
requires biotin (vitamin B7) cofactor and ATP
acetyl-CoA is allosteric activator
- high acetyl-coA concentrations activate the enzyme
- when oxaloacetate levels are low, acetyl-coA cannot enter the TCA cycle
occurs in mitochondria

Question 11

bicarbonate + pyruvate -> __________
enzyme?

Answer 11

oxaloacetate
uses ATP
pyruvate carboxylase

Question 12

once ____________ is produced in the mitochondria, it is transported as _________ into the cytosol, in which __________ is oxidized back to ____________

Answer 12

oxaloacetate; malate; malate; oxaloacetate

Question 13

1st bypass step- reaction 2: synthesis of phosphoenolpyruvate (PEP) from oxaloacetate

Answer 13

enzyme: phosphoenolpyruvate carboxykinase (also called PEPCK)
requires GTP as energy source
mechanism is B-ketoacid decarboxylation
occurs in cytosol

Question 14

2nd bypass step-dephosphorylation of fructose 1,6-bisphosphate to fructose 6-phosphate

Answer 14

enzyme: fructose 1,6-bisphosphatase-1, FBPase-1
highly exergonic hydrolysis– does not require ATP, is irreversible, very favorable
highly regulated
requires Mg2+

Question 15

3rd bypass step- dephosphorylation of glucose-6-phosphate to glucose

Answer 15

enzyme: glucose 6-phosphate
highly exergonic hydrolysis
irreversible
important regulatory step
requires Mg2+
present in liver, renal, and intestinal cells

Question 16

energetics of gluconeogenesis

Answer 16

energetically expensive, but essential
requires 6 ATP equivalents (GTP is energetically equivalent to ATP)

Question 17

downstream products __________, upstream reactants _________

Answer 17

inhibit, stimulate

Question 18

hexokinase I

Answer 18

high glucose affinity, but low capacity (saturation is easy)
allosterically inhibitied by their product

Question 19

hexokinase 4 (aka glucokinase)

Answer 19

low glucose affinity but high capacity
not inhibited by product (G6P) so able to store glucose as glycogen

Question 20

regulation of glycolysis and gluconeogenesis

Answer 20

regulation can be produced through two ways allosteric and hormonal

Question 21

glucagon

Answer 21

signals low glucose levels
peptide hormone made in a-cells in islets of langerhans
acts as a GPCR (high camp) primarily in adipose, liver, and kidney cells
causes liver to release glucose
stimulates glycogenolysis, stops glycogenesis, stimulates gluconeogenesis, and stops glycolysis

Question 22

epinephrine

Answer 22

works similar to glucagon
signals low glucose and/or energy required
fight or flight hormone
acts as B-adrenergic receptors (high camp) in muscle, liver, and adipose
causes liver to release glucose
stimulate glycogenolysis & inhibit glycogenesis

Question 23

insulin

Answer 23

signals high glucose in blood
peptide hormone made in B-cells in islets of langerhans
acts as receptor tyrosine kinase in muscle, liver, and adipose
signals uptake of glucose from blood
increase glycogenesis & inhibit glycogenolysis

Question 24

pyruvate kinase is activated in the liver by _________ and inhibited by __________

Answer 24

insulin; glucagon

Question 25

only in the _______, glucagon can phosphorylate PK by PKA
phosphorylation of PK ________ its activity

Answer 25

liver; inhibits

Question 26

only in the _________, insulin can dephosphorylate PK by PP (phosphatase)
dephosphorylation of PK ________ its activity

Answer 26

liver; stimulate

Question 27

fructose 2,6- bisphosphatase is an allosteric activator for _______ and inhibitor for _________. F-2,6-BP is formed by the phosphorylation of F6P by PFK-2 and dephosphorylated by FBPase-2
PFK-2 & FBPase-2 exist together as a bifunctional enzyme which is under hormonal control

Answer 27

PFK-1; FBPase-2

Question 28

low blood glucose: _________ activates PKA which phosphorylates PFK-2/FBPase-2
activates FBPase-2 & inhibits PFK-2 activity __________ F26BP levels which inhibiting ________ and activates gluconeogenesis

Answer 28

glucagon; decrease; glycolysis

Question 29

high blood glucose: _________ activates PP1, which dephosphorylates PFK-2/ FBPase-2
activates PFK-2 and inhibits FBPase-2 _________ F26BP levels which __________ glycolysis & decreases gluconeogenesis

Answer 29

insulin; increase; activates