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Biochemistry I > Chapter 13: Gluconeogenesis > Flashcards

Chapter 13: Gluconeogenesis Flashcards

1
Q

Gluconeogenesis defined

A
  • Synthesis of new glucose from non-carbohydrate sources
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2
Q

Gluconeogenesis occurs in

A
  • Primarily in the liver

- Also in the kidney cortex

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3
Q

When liver glycogen is depleted

A
  • Gluconeogenesis makes glucose available for the brain and RBCs
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4
Q

ATP input required by gluconeogenesis

A
  • Requires 6 ATP input

- Largely from beta oxidation of fatty acids

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5
Q

Mobilization of fats

A
  • Used in making ATP
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6
Q

Gluconeogenic substrates

A
  • First converted to oxaloacetate
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7
Q

Pyruvate carboxylase (only in mitochondria)

A
  • Converts pyruvate to oxaloacetate in order to bypass
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8
Q

Major non-carbohydrate substrates for gluconeogenesis first converted to oxaloacetate

A
  • Amino acids (ala/glu)
  • CAC intermediates
  • Glycolytic intermediates (Pyruvate, PEP)
  • Lactate
  • Glycerol
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9
Q

Breakdown products of fatty acids, Acetyl-SCoA, and acetate

A
  • No net synthesis of oxaloacetate from the breakdown of these products
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10
Q

Solely ketogenic amino acid residues

A
  • Leucine

- Lysine

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11
Q

Hormone-sensitive lipase

A
  • Mobilizes gluconeogenesis from glycerol originating from stored triacylglycerides
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12
Q

Mobilization of gluconeogenesis from triacylglycerides requires

A
  • Glycerol kinase

- Glycerol-3-phosphate dehydrogenase

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13
Q

All reactions in gluconeogenesis

A
  • All are irreversible and exergonic (spontaneous)
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14
Q

3 irreversible steps in glycolysis that must be bypassed during gluconeogenesis

A
  • Pyruvate kinase (PEP –> pyruvate)
  • PFK-1 (F-6-P –> F-1,6-Bp)
  • Hexokinase (glucose –> G-6-P)
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15
Q

Mitochondrial pyruvate carboxyalse

A
  • Converts pyruvate to oxaloacetate

- Anaplerotic reaction

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16
Q

Oxaloacetate exits the mitochondria as either

A
  • Aspartate (route 1)

- Malate (route 2)

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17
Q

Outside the mitochondria

A
  • Oxaloacetate can continue in gluconeogenesis

- Cytoplasmic PEPCK

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18
Q

Mitochondrial PEPCK

A
  • Converts oxaloacetate to PEP

- PEP can then exit the mitochondria directly through a translocase

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19
Q

Malate dehydrogenase

A
  • Uses up NAD
  • Generates NADH
  • Consequences for glycolytic pathway which will need NAD
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20
Q

Anaplerotic reaction

A
  • Topping off reaction
  • OAA is an intermediate
  • No depleting of the TCA intermediate
  • So it doesn’t want to let OAA go
  • Have to convert it via MDH or aspartate aminotransferserase
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21
Q

Pyruvate kinase is irreversible

A
  • Pyruvate cannot be converted to PEP by reversing this enzyme
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22
Q

Fat is converted to Acetyl Co A

A
  • Required for gluconeogenesis (everything is connected)
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23
Q

Pyruvate carboxylase

A
  • Anaplerotic reaction
  • Converts pyruvate to oxaloacetate (exits the mitochondria as malate or aspartate)
  • Solely in mitochondria
  • Allosteric and biotin-dependent
  • Requires Acetyl-SCoA as an obligate allosteric activator
24
Q

PEP carboxykinase

A
  • Decarboxylation and phosphorylation of oxaloacetate to PEP

- Both cytoplasmic and mitochondrial in humans

25
Q

PEP carboxykinase is over expressed in

A
  • Diabetes

- Leads to hyperglycemia

26
Q

If diabetic and not in the starving state

A
  • Glucose is still being made
27
Q

Mitochondrial pyruvate carboxylase

A
  • Forms OAA from pyruvate
28
Q

NAHD-linked mitochondrial MDH

A
  • Converts OAA to malate
29
Q

Cytosolic MDH

A
  • Reoxidizes malate in the cytosol to OAA
30
Q

OAA is decarboxylated and phosphorylated in the cytoplasm by

A
  • PEP carboxykinase
31
Q

PEP in the cytosol

A
  • Can by converted to fructose-1,6,-bisphosphate by glycolytic enzymes operating in reverse
32
Q

If the cell needs energy

A
  • Glycolytic pathway is favored and gluconeogenesis is inhibited
33
Q

PFK-1 is irreversible and must be bypassed

A
  • Bypass reaction is catalyzed by fructose-1,6-bisphosphate
  • Stimulated by citrate
  • Inhibited by AMP
34
Q

Hexokinase is irreversible and must be bypassed

A
  • Reaction is bypassed by a membrane-bound glucose-6-phosphatase
35
Q

With high km of glucokinase in the liver

A
  • Most glucose will not be phosphorylated and thus exit into circulation
36
Q

Glucose-6-phosphatase

A
  • ER membrane bound enzyme

- Enzyme is absent from muscle tissue

37
Q

Glucose-6-phosphatase absent from muscle tissue

A
  • Causes muscle to use gluconeogenic enzymes to replenish glycogen not maintain BSL
38
Q

Endoplasmic reticulum proteins

A
  • Assist in the formation of glucose

- From cytosolic G-6-P

39
Q

Alcohol oxidation

A
  • Primarily in liver (major site of gluconeogenesis)
40
Q

Alcohol metabolism

A
  • Reduces gluconeogenesis

- Requires NAD+ or produces NADH

41
Q

Cytosolic alcohol dehydrogenase

A
  • Metabolizes ethanol to acetaldehyde
42
Q

Mitochondrial acetaldehyde dehydrogenase

A
  • Converts acetaldehyde to acetate
  • Then to Acetyl-SCoA
  • Then metabolized to CO2 and H2O
43
Q

Alcohol metabolism shifts

A
  • Shifts equilibrium of cytosolic lactate dehydrogenase from pyruvate formation to lactate synthesis
44
Q

Alcohol metabolism favors

A
  • Reduction of oxaloacetate to malate by cytosolic MDH
45
Q

Reduction of oxaloacetate to malate

A
  • Reduces OAA availability for gluconeogenesis
46
Q

Increasing NADH results in

A
  • Decrease in gluconeogenesis

- Leads to hypoglycemia

47
Q

Use of NAD+ by alcohol metabolism

A
  • Impairs metabolism of pyruvate, urates, and fatty acids
  • Reduces gluconeogenesis
  • Leads to alcohol-induced hyperglycemia
48
Q

Alcohol-induced hyperglycemia

A
  • Affects the brain

- Causes a drop in body temperature

49
Q

Defective gluconeogenic activity

A
  • Prevents lactate

- Leads to lactic acidosis and fasting hypoglycemia

50
Q

Under normal circumstances, in mature red blood cells (lacking mitochondria), and exercising muscle (under anaerobic conditions)

A
  • The pyruvate end product of glycolysis is converted to lactate by lactate dehydrogenase
51
Q

Lactate formation

A
  • Reversible, but favored under physiological conditions
52
Q

The Cori Cycle

A
  • Lactate can diffuse out of the muscle cell
  • Can be converted to glucose in the liver
  • Cycle occurs in muscle and red blood cells
53
Q

Gluconeogenesis uses

A
  • Lactate

- Pyruvate

54
Q

Gluconeogenesis primarily uses C-skeletons of

A
  • Alanine

- Glutamate

55
Q

Gluconeogenesis is essential for maintaining

A
  • Blood sugar levels
56
Q

Mobilization of gluconeogenesis from triacylglycerides produces

A
  • Dihydroxyacetone phosphate/DHAP (glycolytic intermediate)
57
Q

PEP carboxykinase synthesis is repressed by

A
  • High glucose diets, but elevated in diabetes mellitus

Biochemistry I (34 decks)

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