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Biochem > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

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1
Q

Function of gluconeogenesis

A

Another mechanism of maintaining blood glucose homeostasis in addition to glycogen degradation

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2
Q

When

A

FASTED state

  • Low I/G as in overnight fast
  • Prolonged exercise
  • High protein, low-carb diet
  • Stress
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3
Q

Where

A

Primary site = liver

Also in kidney to lesser extent

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4
Q

Liver cannot carry out _________

A

Glycolysis and gluconeogenesis at same time at same rate.

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5
Q

Glycolysis ___________ in the fasted state in ________

A

Decreases

the liver

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6
Q

Major non-carbohydrate precursors used as substrates (4)

A
  1. Lactate
  2. Amino acids
  3. Glycerol
  4. TCA cycle intermediates
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7
Q

All TCA cycle intermediates except ______ can be used as substrates in gluconeogenesis

A

Acetyl CoA

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8
Q

Cori Cycle =

A

Lactate recycling

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9
Q

2 functions of lactate dehydrogenase

A
  1. Maintain glycolysis during fed state (especially under anaerobic conditions) by producing NAD+
  2. Provide lactate for gluconeogenesis in fed state
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10
Q

Chemistry of forming pyruvate

Enzyme: lactate dehydrogenase

A

Oxidize -OH group on lactate to C=O —>form pyruvate

NAD+ picks up e- to NADH

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11
Q

Lactic acid produced as a consequence of anaerobic glycolysis in muscle enters blood stream —>

A

Taken up by liver —> converted to pyruvate by lactate dehydrogenase —> pyruvate serves as carbon skeletons for gluconeogenesis

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12
Q

Where does lactate come from? (2)

A
  1. RBC

2. Exercising muscle

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13
Q

Where do amino acids come from?

A

Muscle protein degradation in skeletal muscle

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14
Q

Primary amino acid used to make pyruvate?

How?

A

Alanine

Alanine aminotransferase converts to pyruvate by removing amino group

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15
Q

Where does glycerol come from?

A

Triglyceride breakdown in adipose tissue

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16
Q

Use of glycerol as a substrate

A

Glycerol + ATP —> glycerol phosphate + ADP + Pi (enzyme: glycerol kinase)
* glycerol is from stored TG here

Glycerol phosphate + NAD+ —> dihydroxyacetone phosphate + NADH

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17
Q

Dihydroxyacetone phosphate

A

A glycolytic intermediate

Generated by using glycerol from breakdown of stored triglycerides

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18
Q

_________ carbons cannot be used as substrates for gluconeogenesis

Why?

A

Fatty acid

Most FA carbons only yield acetyl CoA —> acetyl CoA through TCA cycle cannot provide for a net synthesis of sugars because 2 carbons are lost as CO2

Also pyruvate dehydrogenase reaction is irreversible

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19
Q

4 main molecules in order

A

Pyruvate —> OAA —> phosphoenolpyruvate —> glucose

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20
Q

Any ATP is coming from?

A

Oxidation of fatty acids

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21
Q

Glycolysis is shut down because?

A

Pyruvate kinase is phosphorylated and inhibited in fasted state

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22
Q

Retained steps

A

2, 4-9

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23
Q

Replaced steps

24
Q

Step 1

Study These Flashcards
A

Pyruvate + CO2 + ATP + H2O —> OAA + ADP + Pi + 2 H+

Enzyme: pyruvate carboxylase

  • Add CO2 to pyruvate
  • Occurs in mitochondria
25
Pyruvate carboxylase requires
Biotin as a coenzyme for carrier of CO2 Source of CO2 is bicarbonate
26
What provides energy for gluconeogenesis?
Beta-oxidation of fatty acids * must happen at same time
27
Allosteric activators of pyruvate carboxylase
1. Acetyl-CoA : comes from FA oxidation | 2. ATP
28
Step 2
[First, OAA is transported into cytoplasm as malate and OAA is reformed.] OAA +GTP —> Phosphoenolpyruvate + GDP + CO2 Enzyme: phosphoenolpyruvate carboxykinase (PEPCK)
29
Why is GTP needed in PEPCK reaction?
Forming phosphoenolpyruvate which is a high energy molecule
30
Energy for forming PEP is provided by:
1. Hydrolyzing GTP | 2. Decarboxylation is favorable (remove CO2 that pyruvate carboxylase added)
31
Step 3
PEP + H2O 2-phosphoglycerate
32
Step 4
2-phosphoglycerate 3-phosphoglycerate
33
Step 5
3-phosphoglycerate + ATP 1,3-BPG + ADP
34
Step 6
1,3-BPG + NADH Glyceraldehyde-3-phosphate + NAD+ + Pi ***Also dihydroxyacetone phosphate enters here by isomerizing to form glyceraldehyde 3-phosphate
35
Step 7
Glycerol-3-phosphate fructose-1,6-bisphosphate
36
Step 8
****CONTROL POINT**** Fructose-1,6-bisphosphate + H2O —> fructose-6-phosphate + Pi Enzyme: Fructose-1,6-bisphosphatase - Thermodynamically favorable
37
Fructose-1,6-bisphosphate is allosterically inhibited by:
1. Fructose-2,6- bisphosphate | 2. AMP
38
Step 9
Fructose-6-phosphate glucose-6-phosphate
39
Step 10
Glucose-6–phosphate + H2O —> glucose + Pi Enzyme: glucose-6-phosphatase
40
Glucose-6-phosphatase - location - mechanism
- Found in ER membrane - Catalytic domain faces ER lumen Glucose-6-phosphate gets into ER lumen of liver and kidney cells —> P comes off in hydrolysis reaction —> both P and glucose exit lumen —> glucose into blood
41
4 major enzymes in gluconeogenesis
1. Pyruvate carboxylase 2. PEPCK 3. Fructose-1,6-bisphosphatase** 4. Glucose-6-phosphatase
42
3 major enzymes in glycolysis
1. Pyruvate kinase 2. PFK-1** 3. Glucokinase / hexokinase
43
PFK-1 allosteric regulation
Allosterically activated by F-2,6-BP and AMP Allosterically inhibited by ATP
44
Fructose-1,6-bisphosphatase allosteric regulation
Allosterically inhibited by F-2,6-bisphosphatase and AMP
45
Pyruvate allosteric regulation
Activated by fructose-1,6-bisphosphate Inhibited by ATP
46
Phosphoenolpyruvate carboxykinase (PEPCK) allosteric regulation
Inhibited by ADP
47
Pyruvate carboxylase allosteric regulation
Activated by acetyl CoA Inhibited by ADP
48
Glucose-6-phosphatase regulation
Under substrate level control If G-6-P builds up, increase activity of enzyme
49
Fructose-2,6-bisphosphatase is made by ______ in _________
PFK-2 (kinase domain) in fed state
50
In fasted state, PFK-2 is ___________ and ________ active Result:
Phosphorylated and less active Result: Allows FBPase-2 to become more active
51
In fasted state __________ degrades __________
FBPase-2 degrades fructose-2,6-bisphosphate
52
In fed state, insulin signaling activates _________ to _________ PFK-2 to make ____________
In fed state, insulin signaling activates phosphoprotein phosphatase to remove phosphate from PFK-2 to make it active —> make fructose-2,6-bisphosphate
53
FBPase-2 is _________ by fructose-2,6-bisphosphate
Inhibited
54
Need _____ high energy phosphate to make 1, 6-C glucose Where do they come from?
6 2 ATP in Pyruvate carboxylase reaction 2 GTP in PEPCK reaction 2 ATP as 2 moles of 3-phosphoglycerate —> 2 mol 1,3-BPG
55
ATP in fasted state
NOT limited Why? —> Fatty acids give more ATP than glucose
56
Glycolysis = ________ energy Gluconeogenesis = _________ energy
Glycolysis releases energy (ATP and NADH) Gluconeogenesis consumes ATP and NADH
57
Glycolysis and gluconeogenesis are ________ regulated.
Reciprocally

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