Gluconeogenesis

Question 1

when does it occur?

Answer 1

long term fasting
starvation
glycogen depletion typically occurs by 12-30 hrs of fasting

Question 2

why does it occur?

Answer 2

some tissues can only/primarily use glucose for energy

RBC, brain, nervous tissue, kidney medulla, eye lens and cornea

Question 3

Where does it occur?

Answer 3

Liver primarily

bc most tissues (brain, muscle) lack Glucose-6-phosphatase required to release glucose form cells

Question 4

What is the mechanism?

Answer 4

reversal of glycolysis

irreversible steps 1,3,10 uses non-glycolytic enzymes

Question 5

precursors of glucose synthesis

Answer 5

lactate - RBC
Glycerol - Adipose
AA- Alanine , muscle
Propionate - minor, 3C from oxidation of odd chain FA

Question 6

4 enzymes that circumvent the irreversible steps of glycolysis

Answer 6

Pyruvate Carboxylase
PEP carboxykinase
fructose phosphatase
glucose-6-phosphatase

Question 7

Where in the cell can pyruvate carboxylase be found?

Answer 7

mitochondria

Question 8

what rxn does pyruvate carboxylase catalyze?

Answer 8

pyruvate–> OAA
uses ATP and CO2
which leaves mitochondria thru malate-asparate shuttle
can be malate or aspartate intermediate

Question 9

Pyruvate carboxylase requires what coenzyme in order to function

Answer 9

Biotin

Question 10

Where in the cell can PEP carboxykinase be found?

Answer 10

Cytosol

Question 11

What reaction does PEP carboxykinase catalyze?

Answer 11

OAA –> PEP

using GTP

Question 12

Major manifestation of PEP carboxykinase deficiency?

Answer 12

hypoglycemia after fasting

Question 13

where in cell can fructose 1,6-bisPhosphatase be found?

Answer 13

cytosol

Question 14

What rxn does fructose 1,6-bisPhosphatase catalyze?

Answer 14

fructose 1,6bisP to fructose 6-P
hydrolysis
release Pi

Question 15

Where in cell can glucose 6-Phsophatase be found?

Answer 15

cytosol of liver only

Question 16

What rxn does glucose 6-Phosphatase catalyze?

Answer 16

glucose 6-P –> glucose
hydrolysis
release Pi

Question 17

Glucose 6-phosphatase deficiency is known as what disorder?

Answer 17

Von Gierke disease

Question 18

hormone that is the main regulator of gluconeogenesis?

Answer 18

glucagon

Question 19

how does glucagon exert allosteric regulation on gluconeogenesis?

Answer 19

glucagon decreases levels of fructose-2,6 bisP

activating fructose 1,6-bisphosphatase and inhibits PFK 1

Question 20

How does glucagon regulate pyruvate kinase?

Answer 20

glucagon increases levels of cAMP
increases PKA activity
Pyruvate kinase phosphorylated = Inactive

Question 21

How does inactivation of pyruvate kinase alter level of gluconeogenesis that occurs?

Answer 21

decreases amt of active pyruvate kinase
decreases conversion of PEP –> pyruvate
diverts PEP toward glucose

Question 22

How can a decrease in insulin alter gluconeogensis?

Answer 22

decreased insulin favors mobilization of AA from muscle to liver
carbon skeletons are used for gluconeogenesis

Question 23

During starvation, which molecule acts as an activator of gluconeogeneis?

Answer 23

Beta oxidation of FA during starvation increases amt of Acetyl CoA
exceeding the capacity of liver to oxidize it to CO2
excess acetyl CoA activates pyruvate carboxylase activity

Question 24

Which by product of exercising or ischemic muscle is used for gluconeogenesis?

Answer 24

Lactate

Question 25

Which process describes the movement of gluconeogenic substrates btw muscle and liver?

Answer 25

Cori cycle

Question 26

gluconeogenic precursors

Answer 26

``` galactose, glycogen --> glucose 6P fructose --> DHAP Fat--> glycerol 3P Muscle-- AA for TCA intermed, AA--> pyruvate , RBC- lactate--> pyruvate ```

Question 27

gluconeogenesis free energy

Answer 27

-9 kcal/mol | requires 4 more ATP/GTP to make the rxn favorable

Question 28

Cori Cycle

Answer 28

O2 insufficient RBC/Muscle Liver anerobic glycolysis gluconeogenesis

Question 29

Cori Cycle rxn

Answer 29

2 lactate + 4 ATP + 2GTP = 1 glucose

Question 30

Alanine Cycle

Answer 30

Muscle Cell Liver | glycolysis gluconeogenesis

Question 31

Alanine Cycle

Answer 31

2 alanine + 8 ATP + 2 GTP = 1 glucose

Question 32

Favorable conditions for gluconeogenesis

Answer 32

Fasting- glucagon = phosphorylate enzymes Prolonged exercise High protein/ low carbohydrate diet Stress hormones- phosphorylate enzymes

Question 33

Insulin

Answer 33

pancreatic beta cells stimulated by blood glucose binds to cell membrane receptor in responsive cells promotes fuel storage and growth

Question 34

Insulin stimulates

Answer 34

protein synthesis glucose and AA transport into cells reverses glucagon stimulated phosphorylation

Question 35

Glucagon

Answer 35

pancreatic alpha cells pressed by blood glucose and insulin stimulated by EPI, Cortisol, AA mobilize stored fuels - gluconeogenesis, glycogenolysis , fatty acid release

Question 36

Glucagon stimulates

Answer 36

cascade resulting in Protein phosphorylation activates glycogen degradation activates gluconeogenesis inhibits glycogen synthesis

Question 37

Epinephrine

Answer 37

mobilize sotred fuels glucose production fatty acid release

Question 38

Cortisol

Answer 38

changing requirements over long term AA mobilization from muscle gluconeogenesis (liver) fatty acid release

Question 39

Insulin release

Answer 39

GLUT2 glucose transporter- high Km moves glucose in cell glycolysis, TCA, oxidative phosp --> increase in ATP inc ell inhibit K+ channel, activate Ca2+ channels Ca2+ influx Vesicle fusion and exocytosis release of Protein Phosphatase 1 (PP1)

Question 40

Pyruvate carboxylase regulated by

Answer 40

``` acetyl coA (+) from FA oxidation ```

Question 41

Phosphoenolyruvate carboxykinase (PEPCK) regulated by

Answer 41

glucagon, EPI, cortisol (+) | insulin (-)

Question 42

fructose bisphosphatase regulated by

Answer 42

F-2,6-P (-) AMP (-) citrate (+)

Question 43

Regulation of PKA

Answer 43

glucagon , EPi stimulates Adenylate cyclase cascade | cAMP -PKA

Question 44

Fructose 2,6 bisphosphate

Answer 44

allosteric regulator of PFK1 and fructose bisphosphatase glucagon- PKA phosphorylate PFK2 thus inactivates F-2,6-bisPase and inhibits PFK 1 ==> gluconeogenesis insulin - PPI dephosphorylates PFK-2 thus activates F-2,6,bisPase and activates PFK1 ==> glycolysis

Question 45

PFK-2/F-2,6-bisPase differences in liver and cardiac muscles

Answer 45

Liver (glucagon) and cardiac muscle (EPI) are opposite PKA--> PFK2-P liver= inhibit F2,6bisPase decrease glycolysis cardiac muscle = activate F2,6bisPase increases glycolysis