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FHB Exam 3 > Metabolism: Gluconeogenesis > Flashcards

Metabolism: Gluconeogenesis Flashcards

1
Q

What is the most important enzyme in glucose homeostasis?

A

glucose-6-phosphatase
only found in the liver
required for both glycogenolysis and gluconeogenesis

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2
Q

List the 5 stages of glucose homeostasis.

A
  1. exogenous glucose
  2. glycogenolysis (requires less time than fatty acid oxidation; the more stores the better)
  3. starting gluconeogenesis
  4. gluconeogenesis
  5. gluconeogenesis - but brain is running on ketone bodies
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3
Q

What are the major gluconeogenic precursors?

A

pyruvate
lactate
glucogenic AAs
glycerol

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4
Q

How much energy is required for gluconeogenesis?

A

6 ATP if Cori Cycle (lactate)

10 ATP if Alanine Cycle (alanine)

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5
Q

What activates gluconeogenesis?

A
  • hypoglycemia (exogenous glucose has been oxidized)
  • lack of glycogen stores
  • glucagon/epinephrine
  • low NADH
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6
Q

Describe the Cori Cycle.

A
  • lactate produced by RBC and skeletal muscle metabolism
  • converted to pyruvate in the liver via LDH
  • 2 lactate => 1 glucose
  • glucose released into circulation for cells who need more
  • requires 6 ATP
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7
Q

Describe the Alanine Cycle.

A
  • alanine produced from skeletal muscle protein metabolism
  • converted to glucose in the liver
  • 2 alanine => 1 glucose
  • requires 10 ATP (4 extra ATP because must convert NH3 to urea)
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8
Q

How does alanine differ from aspartate in gluconeogenesis?

A

alanine is converted to pyruvate

asparatate is directly converted to OAA (1 less step)

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9
Q

Describe how glycerol contributes to gluconeogenesis.

A
  1. glycerol is the product of TAG breakdown

2. becomes DHAP

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10
Q

What are alternative sources of glucose?

A
  • fructose undergoes fructolysis (F => F1P => GAP/DHAP)

- galactose gets converted to glucose (gal => G6P)

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11
Q

Why is PEP carboxykinase important at birth?

A
  • not active at birth, requires a few hours to induce

- until then, baby can be hypoglycemic because can’t create PEP to enter gluconeogenesis

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12
Q

What is the mechanism of glycerol entering gluconeogenesis?

A
  1. glycerol => glycerol-3-phosphate (glycerol kinase, ATP)
  2. glycerol-3-phosphate => DHAP (glycerol-3-phosphate dehydrogenase)
    NOTE: some glycerol-3-phosphate goes on to make fatty acids
  3. yields 1/2 glucose and 1 lactate
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13
Q

Can you use acetyl-CoA to make glucose?

A

No, because it is determined to go into TCA or fatty acid synthesis

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14
Q

What is the mechanism of propionate entering gluconeogenesis?

A
  1. odd-chained fatty acid beta oxidation yields propionyl-CoA
  2. converted to OAA
  3. yields 1/2 glucose and 1 lactate
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15
Q

What are the 4 regulatory enzymes for gluconeogenesis?

A
  1. mitochondrial pyruvate carboxylase
  2. cytoplasmic PEP carboxykinase
  3. cytoplasmic F16BPase
  4. cytoplasmic G6Pase
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16
Q

Describe the reaction carried out by pyruvate carboxylase.

A
  • converts pyruvate to OAA
  • only occurs in the mitochondria
  • OAA is then converted to malate to be transported to the cytoplasm, where it is remade into OAA
  • requires: biotin and ATP
17
Q

What are the symptoms and associated manifestations of pyruvate carboxylase deficiency?

A

Symptoms

  • failure to thrive
  • developmental delays
  • recurrent seizures
  • metabolic acidosis

Manifestations

  • accumulation of lactate and alanine b/c can’t convert pyruvate
  • prevents gluconeogenesis
18
Q

Describe the reaction carried out by PEPCK

A
  • converts OAA to PEP

- requires GTP

19
Q

Describe the reaction carried out by F16BPase

A
  • converts F16BP to F6P
20
Q

Describe the relationship between PFK1 and F16Bpase.

A
  • recall that glycolysis and gluconeogenesis are reciprocally regulated
  • PFK1 is activated by F26BP => promotes glycolysis
  • hence, F26BP will inhibit gluconeogenesis by inhibited F16BPase
21
Q

Describe the reaction carried out by G6Pase.

A
  • converts G6P to Glucose

- occurs in the liver; both glycogenolysis and gluconeogenesis require it

22
Q

Where is G6Pase found?

A
  • lumen of the ER in liver, kidney, and intestinal cells
23
Q

How does G6Pase work?

A
  • G6P enters the ER via ubiquitinous transporter
  • G6Pase converts to glucose and Pi
  • exits lumen via transporters
24
Q

Describe the symptoms and etiology of von Gierke disease. What are some other names for it?

A
  • glycogen storage disease type 1 (G6Pase deficiency)
  • accumulation of glycogen in the liver, but can’t break it down to make glucose
  • poor tolerance of fasting
  • growth retardation
  • hepatomegaly
  • prevents gluconeogenesis and glycogenolysis
25
Q

What regulates F16BPase?

A

inhibited by: F26BP and AMP

26
Q

What regulates PEPCK?

A

activated by: glucagon

inhibited by: insulin

27
Q

What regulates G6Pase?

A

activated by: glucagon

inhibited by: insulin and glucose

28
Q

What regulates pyruvate carboxylase?

A

activated by: acetyl-CoA

29
Q

What regulates glucokinase/hexokinase?

A

activated by: insulin and glucose

30
Q

What regulates PFK1?

A

activated by: F26BP and AMP

inhibited by: ATP and citrate

31
Q

What regulates pyruvate kinase?

A

activated by: F16BP and glucose

inhibited by: glucagon and ATP and alanine

32
Q

In general, what increases synthesis of glycolytic enzymes?

A
  • insulin, glucose
  • decreased glucagon/epi => decreased cAMP
  • low energy
33
Q

In general, what increases synthesis of gluconeogenic enzymes?

A
  • glucagon/epi

- increased cAMP => PKA => cAMP Response Element Binding Protein (CREBP)

34
Q

Why does ethanol consumption cause hypoglycemia?

A
  • ethanol is converted to acetaldehyde via ethanol dehydrogenase
  • this reaction produces lots of NADH
  • increased NADH/NAD ratio inhibits gluconeogenesis/glycogenolysis
  • NADH pushes pyruvate => lactate
  • NADH pushes OAA => malate
  • not enough available substrates for gluconeogenesis

FHB Exam 3 (23 decks)

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