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Biochem ENDO > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

gluconeogenesis

  • depends on what precurors
  • occurs in what tissues?
  • is especially important for what tissues?
A
  • synthesis of glucose from:
    • pyruvate
    • lactate
    • alanine
    • glycerol
    • propionate
  • takes place in the:
    • liver (90%)
    • kidney (10%)
  • is key for:
    • brain
    • RBCs
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2
Q

what are the irreversible steps of gluconeogenesis?

A
  1. pyruvate –> OAA
  2. OAA –> PEP
  3. the subsequent glycolytic steps that are irreversible:
    1. F-1,6-BP –> F-6-P
    2. G-6-P –> glucose
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3
Q

pyruvate –> OAA

  • catalyzed by what enzyme?
  • in what part of the cell?
  • requires what substrates and cofactors?
  • regulated by?
A
  • enzyme: pyruvate carboxylase (in the mitochondria)
  • requires:
    • ATP
    • biotin
  • regulated by: acetyl CoA
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4
Q

biotin

has a key role in what gluconeogenic step?

how does it work?

A
  • pyruvate –> OAA (1st irreverisble step)
  • biotin serves as a carrier for activated CO2:
    • CO2-biotin-pyruvate carboxylase complex forms using energy from ATP hydrolysis
    • activated CO2 transferred to pyruvate to form OAA
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5
Q

what is the next gluconeogenic step after OAA is synthesized?

A
  • OAA must be transported out of the mitochondria, across the mitochondiral membrane, and into the cytosol. this occurs with malate-asparate shuttle
    1. OAA is transaminated to aspartate asparatate transaminase
    2. aspartate crosses over IMM into cytosol
    3. aspartate deaminated back to OAA
    4. OAA reduced back to malate
    5. malate crosses back into mitochondria, where it feeds back into OAA and the citric acid cycle
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6
Q

what happens to OAA after it is moved to the cytosol?

A

OAA –> PEP (glycolic molecule) by PEP carboxykinase (phosphoenopyruate carboxykinase)

  • 2nd irreversible gluconeogenic reaction
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7
Q

OAA –> PEP

  • catalyzed by what enzyme?
  • occurs in what parts of the cells?
  • requires what cofactors?
A
  • PEP carboxylase
  • in the cytosol
  • requires: GTP
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8
Q

what occurs to PEP after it is synthesized in the cytosol?

A

PEP –> F-1,6-BP (glycolitic molecule).

since we are now in the glycolytic path, several glycolytic steps are involved in this conversion (none are irreverisble)

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9
Q

PEP –> F, 16 -BP

  • catalyzed by what enzyme?
  • occurs where?
  • requires what substrates/cofactors
A
  • several irreversible glcyolytic enzymes
  • in cytosol
  • not important
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10
Q

what occurs to F -1, 6-BP after its synthesis?

A

F-1,6-BP –> F-6-P by fructose-1,6-bisphosphotase

  • 3rd irreversible gluconeogenic step
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11
Q

F-1,6-BP –> F-6-P

  • catalyzed by what enzyme?
  • occurs where?
A
  • F-1,6-bisphosphotase - major gluconeogenic control point
  • requires H20
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12
Q

what occurs to F-6-P after its synthesis?

A
  • F-6-P –> G-6-P –> glucose by:
    • a reversible glycolytic enzymes
    • glucose-6-phosphotase
      • 4th irreversible gluconeogenic step
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13
Q

G-6-P –> glucose

  • catalyzed by what enzyme?
  • occurs where?
  • requires what substrates/cofactors?
A
  • by glucose-6-phosphotase - an endoplasmic recitculum enzyme
  • occurs in the cytosol of the LIVER and KIDNEY only
  • n/a.
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14
Q

at what gluconeogenic step do we enter the reverse glycolysis pathway?

what enzyme catalyzes this step?

what is the significance of this step?

A
  • generation of PEP
    • OAA –> PEP (PEP carboxykinase + GTP)
    • this bypasses pyruvate kinase, which is necessary because there is no reverse reaction for PEP–> pyruvate (i.e., no way to convert pryruvate to PEP). thus, we must convert pyruvate to OAA, and OAA to PEP.
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15
Q

review the irreversible gluconeogenic enzymes.

  • what steps do they each catalyze?
  • what cofactors/substrates do they rely on?
A
  1. pyruvate –> OAA. pyruvate carboxylase + CO2 + ATP + biotin [mitochondria]
  2. OAA –> PEP. PEP carboxykinase + GTP
  3. F-1,6-BP –> F-6-BP. fuctose-1-6-bisphosphotase + H20
  4. G-6-P –> glucose. by glucose-6-phosphotase [endoplasmic reticulum]
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16
Q

which gluconeogenic enzyme is an endoplasmic rectilar enzyme?

where is it found?

A
  • glucose-6-phosphotase
  • found only in the liver and kidney
17
Q

how many pyruvate molecules are needed to generate one glucose molecule?

per the generation of this one glucose molecule - how much total energy is used? at what gluconeogenic steps it his energy used?

A
  • 2 pyruvate molecules per 1 glucose molecule
    • 6 high energy phosphate bonds total:
      • 4 ATP:
        • 2 ATP at pyruvate –> OAA (pyruvate carboxykinase)
        • 2 ATP used at 3-PG-> 1,3-BPG (glycolitic enzyme)
      • 2 GTP :
        • at OAA –> PEP (PEP carboxykinase)
18
Q

discuss the major glycolytic points that are allosterically regualated.

list the regulators at each point.

A
  • hexokinase
    • inhibited by G-6-P
  • PFK-1
    • stimulated by AMP
    • inhibited:
      • ATP
      • citrate
  • PK
    • stimjated by F-1,6-BP
    • inhibited by alanine
19
Q

dicsuss the major gluconeogenic points that are allosterically regulated

list the regulators at these points

A
  • pyruvate carboxylase
    • ​stimulated by acetyl-CoA
  • F-1-6-bisophosphotase:
    • inhibited by AMP
20
Q

ATP and AMP regulate what glycolytic/gluconeogenic points?

A

ATP

  • inhibits PFK-1 and PK

AMP

  • stimulates PFK-1
  • inhibits F-1,6-BP
21
Q

discuss the hormonal regulation of glycolysis and gluconeogenesis.

what hormones are involved?

at what biochemical step(s)?

A
  • regulation by insulin and glucagon
    • insulin:
      • promotes glycolysis
      • inhibits gluconeogenesis
    • glucagon
      • promotes gluconeogenesis
      • inhibits glycolysis
  • largely exerted at the level of:
    • F-6-P –> F-1,6-BP
    • PEP –> pyruvate
22
Q

how do hormones regulate F-6-P–> F-1,6-BP?

A
  • by effect son PFK-1 and F-1,6-bisphosphotase
    • insulin increases presence of F-2,6-BP, which acts feedback. it wil ​
      • inbibit F-1,6 bisphosphotase
      • ​stimulate PFK-1 (feed-forward)
23
Q

how do hormones regulate PEP –> pyruvate?

A
  • by acting on pyruvate kinase:
    1. insulin –> desphophorylates & activate PK –> glycolysis proceeds
    2. glucagon –> phosphorylates & inactivates PK –> guconeogenesis can proceed
      • via binding of Gs receptor –> cAMP
    3. epinephrin (in the liver*) = acts like glucagon
      • via binding of Gs receptor –> cAMP
24
Q

what hormomones exert metabolic effects through cAMP pathway?

how do they do this?

A
  1. glucagon
  2. epinephrine

via binding of Gs GCPR

promotes gluconeogenesis

25
Q

in what tissues is lactate the end product of glycolysis?

A

erythrocytes (RBCs)

26
Q

lactate as a gluconeogenic precursor

  • what tissues produce a significant amount of lactate?
  • how does lacate feed into gluconeogenesis?
A
  • from RBCs​ & muscle - RBCs only undergo anaerobic glycolysis (no mitochondria), muscle often does during fasting/exercise
  • feeds in @ pyruvate via oxioreductase activity
27
Q

alanine as a gluconeogenic precursor

  • comes in from what source?
  • feed into gluconeogenesis how?
A
  • from muscle - is an amino acid
  • feeds in @ pyruvate via deaminination (transaminase activity)
28
Q

glycerol as a gluconeogenic substrate

  • comes from what source?
  • feeds into gluconeogenesis how?
A
  • from adipose tissue via triacylglycerol release
  • enters @ the level of DHAP (glycolysis portion) via 1. phosphorylation then 2. dehyrogenation
29
Q

In Diabetes mellitus, TCA cycle is suppressed due to depletion of a substrate. Which substrate is depleted and why?

A

diabetes mellitus: l_ack of insulin_ —> promotes gluconeogenesis and overrides gycolysis. instead of being used as a TCA intermediate, OAA is directed to gluconeogenis, feeding gluconeogenic substrates into gluconeogenic path

  • OAA –> PEP –> ect
30
Q

propionyl CoA as a gluconeogenic substrate

  • comes from what source?
  • feeds into glycolysis how
A
  • from fatty acid synthesis
  • feeds in @ OAA by via TCA cycle as succinyl CoA (several rxns convert propionyl CoA to succinyl oA) ​

Biochem ENDO (13 decks)

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