Lecture 303: gluconeogenesis Flashcards

1
Q

gluconeogenesis

A
  • biosynthesis of glucose from non-carbohydrate substrates [pyruvate]
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2
Q

g of glucose needed by entire body/ brain/ in storage

A
  • body 160g
  • brain needs 120g
  • body has 210g glucose reserves
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3
Q

where is glucose synthesized

A
  • liver
  • one precursor generated in mitochondria
  • glucose generated in ER
  • transported into cytosol [predominates here]
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4
Q

3 irreversible steps of glycolysis bypassed during gluconeogenesis

A
  • 2 enzymes needed for pyruvate kinase
  • 1 enzyme needed for PFK-1
  • 1 enzyme needed for hexokinase
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5
Q

step 1

A
  • bypassing pyruvate kinase
  • done via pyruvate carboxylase and PEPCK
  • pyruvate carboxylase REQUIRES ATP
  • pyruvate carboxylase creates oxaloacetate in mitochondria = taken into cytosol via malate dehydrogenase
  • PEPCK REQUIRES GTP AND IS REGULATED
  • PEPCK acts in decarboxylation of oxaloacetate to PEP
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6
Q

step 2

A
  • PEP converted to F1,6BP via glycolytic enzymes

- entire energy investment here

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7
Q

step 3

A
  • bypass PFK-1 to convert F1,6BP to F6P via F1,6BPase
  • most important step in gluconeogenesis
  • regulated
  • removes Pi group from C1
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8
Q

step 4

A
  • isomerize [synthesize] F6P to G6P via glycolytic enzymes
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9
Q

step 5

A
  • bypass glucokinase and hexokinase to convert G6P to glucose via G6Pase
  • remove Pi group from C6
  • in endoplasmic reticulum
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10
Q

G6Pase found primarily

A
  • liver
  • kidney cortex
  • organs that need glucose as primary carbon source DO NOT express G6Pase [can’t synthesize glucose]
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11
Q

G6Pase deficiency

A
  • Von Gierke Disease
  • severe hypoglycemia
  • enlarged liver
  • growth failure, increased infection risk, impaired blood clotting, neurodevelopmental delay
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12
Q

non-pyruvate starting points

A
  • lactate, glutamine or alanine precursor to pyruvate
  • glutamine or propionate precursor to oxaloacetate
  • glycerol precursor to steps leading up to F1,6BP
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13
Q

role of PEPCK in kidney cortex

A
  • gluconeogenesis to detox ammonia
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14
Q

role of PEPCK in adipose tissue

A
  • adipose incapable of complete gluconeogenesis [lacks G6Pase]
  • PEP produced by PEPCK converted to G3P [glyceroneogenesis]
  • high levels of PEPCK leads to obese mice because of increased fat synthesis [inc. triacylglycerol content]
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15
Q

role of PEPCK in skeletal muscle

A
  • skeletal muscle incapable of complete gluconeogenesis [lacks G6Pase]
  • PEPCK in high amounts led to freaky mice
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16
Q

additional intermediate in gluconeogenesis NOT included in glycolysis

A

oxaloacetate

17
Q

G6Pase found in ____ and not in ____

A
  • found in liver and kidney cortex

- not found in brain or muscle

18
Q

gluconeogenesis precursors

A
  • lactate
  • glycerol
  • almost all AA especially alanine and glutamine but exception to leucine and lysine