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BCH MEtabolism > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

when does it occur?

A

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

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2
Q

why does it occur?

A

some tissues can only/primarily use glucose for energy

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

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3
Q

Where does it occur?

A

Liver primarily

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

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4
Q

What is the mechanism?

A

reversal of glycolysis

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

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5
Q

precursors of glucose synthesis

A

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

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6
Q

4 enzymes that circumvent the irreversible steps of glycolysis

A

Pyruvate Carboxylase
PEP carboxykinase
fructose phosphatase
glucose-6-phosphatase

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7
Q

Where in the cell can pyruvate carboxylase be found?

A

mitochondria

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8
Q

what rxn does pyruvate carboxylase catalyze?

A

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

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9
Q

Pyruvate carboxylase requires what coenzyme in order to function

A

Biotin

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10
Q

Where in the cell can PEP carboxykinase be found?

A

Cytosol

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11
Q

What reaction does PEP carboxykinase catalyze?

A

OAA –> PEP

using GTP

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12
Q

Major manifestation of PEP carboxykinase deficiency?

A

hypoglycemia after fasting

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13
Q

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

A

cytosol

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14
Q

What rxn does fructose 1,6-bisPhosphatase catalyze?

A

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

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15
Q

Where in cell can glucose 6-Phsophatase be found?

A

cytosol of liver only

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16
Q

What rxn does glucose 6-Phosphatase catalyze?

A

glucose 6-P –> glucose
hydrolysis
release Pi

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17
Q

Glucose 6-phosphatase deficiency is known as what disorder?

A

Von Gierke disease

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18
Q

hormone that is the main regulator of gluconeogenesis?

A

glucagon

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19
Q

how does glucagon exert allosteric regulation on gluconeogenesis?

A

glucagon decreases levels of fructose-2,6 bisP

activating fructose 1,6-bisphosphatase and inhibits PFK 1

20
Q

How does glucagon regulate pyruvate kinase?

A

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

21
Q

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

A

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

22
Q

How can a decrease in insulin alter gluconeogensis?

A

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

23
Q

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

A

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

24
Q

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

A

Lactate

25
Q

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

A

Cori cycle

26
Q

gluconeogenic precursors

A 
galactose, glycogen --> glucose 6P 
fructose --> DHAP 
Fat--> glycerol 3P 
Muscle-- AA for TCA intermed, AA--> pyruvate , 
RBC- lactate--> pyruvate
27
Q

gluconeogenesis free energy

A

-9 kcal/mol

requires 4 more ATP/GTP to make the rxn favorable

28
Q

Cori Cycle

A

O2 insufficient
RBC/Muscle Liver
anerobic glycolysis gluconeogenesis

29
Q

Cori Cycle rxn

A

2 lactate + 4 ATP + 2GTP = 1 glucose

30
Q

Alanine Cycle

A

Muscle Cell Liver

glycolysis gluconeogenesis

31
Q

Alanine Cycle

A

2 alanine + 8 ATP + 2 GTP = 1 glucose

32
Q

Favorable conditions for gluconeogenesis

A

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

33
Q

Insulin

A

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

34
Q

Insulin stimulates

A

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

35
Q

Glucagon

A

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

36
Q

Glucagon stimulates

A

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

37
Q

Epinephrine

A

mobilize sotred fuels
glucose production
fatty acid release

38
Q

Cortisol

A

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

39
Q

Insulin release

A

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)

40
Q

Pyruvate carboxylase regulated by

A 
acetyl coA (+) 
from FA oxidation
41
Q

Phosphoenolyruvate carboxykinase (PEPCK) regulated by

A

glucagon, EPI, cortisol (+)

insulin (-)

42
Q

fructose bisphosphatase regulated by

A

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

43
Q

Regulation of PKA

A

glucagon , EPi stimulates Adenylate cyclase cascade

cAMP -PKA

44
Q

Fructose 2,6 bisphosphate

A

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

45
Q

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

A

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

BCH MEtabolism (8 decks)

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