ME03 - GLUCONEOGENESIS

Question 1

Synthesis of carbohydrates from non-carbohydrate sources
Such as:
intermediatesofglycolysisandtheTCA
glycerolfromtriacylglycerols
lactatethroughtheCoriCycle carbonskeletons(α ketoacids) of glucogenic amino acids

Answer 1

GLUCONEOGENESIS
“Gluconeogenesis means to make new glucose. “Neogenesis, you’re going to make new memories. It is the reversibility of glycolysis. For you to undo something, you need to put conscious effort with it. Time. Energy.

Question 2

Three non-equilibrium reactions in glycolysis, catalyzed by ______ ,_______ and _______, prevent simple reversal of glycolysis.

Answer 2

hexokinase, phosphofructokinase and pyruvate kinase

Question 3

Glycogen synthesis involves a different pathway via

Answer 3

uridine diphosphate glucose and glycogen synthase

Question 4

Biomedical Importance of Gluconeogenesis

Answer 4

To supply glucose to the following when glycogen
supply has been depleted:
! Brain and erythrocytes
! Contracting skeletal muscles ! Fetus in pregnancy
! Lactating mammarygland
! Retina,lens,renalmedulla

o To clear products of metabolism
! Lactate and glycerol–waste products that are
recycled by the body back to glucose reflecting
cellular economy

Question 5

Where does it occur?

Answer 5

Occurs in the liver (90%) and the kidney (10%)
o During prolonged fasting, the kidneys contribute as
much as 40%
o Occurs in both mitochondria and cytoplasm

Question 6

What is the substrate?

Answer 6

Pyruvate
Glycerol
• Adipocytes cannot phosphorylate glycerol
because they lack glycerol kinase Lactate
• Released from exercising skeletal muscles and cells that lack mitochondria
Propionate
• Precursor of glucose in ruminants, enters
via the citric acid cycle

Question 7

Enzymes involved in Gluconeogenesis

Answer 7

Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase

Question 8

Enzyme during the UNFED STARVING PHASE

Answer 8

Pyruvate carboxylase

Catalyzesthecarboxylationofpyruvateto
oxaloacetate
• ATP-requiring reaction; vitamin biotin as
coenzyme that will bind to CO2
• The resultant oxaloacetate is reduced to
malate, exported from the mitochondrion into the cytosol and there oxidized back to oxaloacetate

Question 9

Decarboxylationandphosphorylationof oxaloacetate to phosphoenolpyruvate

Answer 9

Phosphoenolpyruvate carboxykinase

Question 10

Conversionoffructose1,6-bisphosphateto
fructose 6-phosphate
! Determinescapabilityofsynthesizingglucose
from pyruvate and triose phosphates

Answer 10

Fructose 1,6-bisphosphatase

Liver,kidney,andskeletalmuscle

Question 11

Conversionofglucose6-phosphatetoglucose ! Liverandkidney

Answer 11

Glucose 6-phosphatase

Question 12

Reactions unique to gluconeogenesis

Answer 12

Carboxylation of pyruvate
Transport of oxaloacetate to the cytosol
Decarboxylation of cytosolic oxaloacetate
Dephosphorylation of fructose 1,6-biphosphate
Dephosphorylation of glucose 6-phosphate

Question 13

Transport of oxaloacetate to the cytosol

Answer 13

OAAisunabletodirectlycrosstheinner
mitochondrial membrane
! Mustbereducedfirsttomalatebymitochondrial
malate dehydrogenase
! Malatecanbetransportedfromthemitochondria to the cytosol, where it is reoxidized to oxaloacetate by cytosolic malate dehydrogenase

Question 14

Decarboxylation of cytosolic oxaloacetate

Answer 14

Oxaloacetateisdecarboxylatedand
phosphorylated in the cytosol by PEP-
carboxykinase (PEPCK)
! ReactiondrivenbyhydrolysisofGTP

Question 15

Dephosphorylation of fructose 1,6-biphosphate

Answer 15

Regulationbyfructose2,6-bisphosphate
• Fructose 2,6-bisphosphate inhibits fructose 1,6-bisphoosphatase
• An allosteric modifier whose concentration is influenced by the level of circulating glucagon
• NOTE: Recall that fructose 2,6-bisphosphate activates PFK-1 of glycolysis

Question 16

Only organs that release

free glucose from glucose 6-phosphate

Answer 16

Liver and kidney

Question 17

two enzymes for the Dephosphorylation of glucose 6-phosphate

Answer 17

Glucose 6-phosphate translocase which transports glucose 6-phosphate across the endoplasmic reticular (ER) membrane

Glucose 6-phosphatase found only in gluconeogenic cells which removes the phosphate, producing free glucose
• NOTE: These enzymes are required for the final step in glycogenolysis, as well as gluconeogenesis

Question 18

This is the rate-limiting step of gluconeogenesis

Answer 18

Step 3: Fructose-1,6-BP > Fructose-6-P

Activates phosphofructokinase-1 > favors glycolysis

Inhibits
F-1,6-bisphosphatase > inhibits gluconeogenesis

o Activator: ATP
o Inhibitor: Fructose-2,6-BP and AMP