Module 10: Carbohydrate Metabolism - Gluconeogenesis (Part 02) Flashcards

1
Q

This is the synthesis of glucose from non-carbohydrate precursors.

A

Gluconeogenesis

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2
Q

Why is gluconeogenesis important?

A

(1) Essential for human survival
(2) Maintains blood glucose levels to support metabolism of tissues that use glucose as their primary substrate
(3) Supplies glucose after glycogen has almost been depleted

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3
Q

This is the main site for gluconeogenesis, it is involved in the control of systemic blood glucose.

A

Liver

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4
Q

What is the main site during fasting and starvation?

A

Kidneys (Renal Cortex)

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4
Q

How much gluconeogenesis occurs in the liver?

A

50%

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5
Q

How much percentage of newly synthesized glucose molecules does the Kidneys (Renal Cortex) provide?

A

10%

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6
Q

What are the sites for gluconeogenesis?

A

(1) Liver
(2) Kidneys (renal cortex(
(3) Small intestine - epithelial cells

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6
Q

What are the major substrates of gluconeogenesis?

A

(1) glucogenic AA,
(2) lactate,
(3) glycerol,
(4) fructose, and
(5) propionate

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7
Q

What are the major gluconeogenic tissues?

A

Liver and kidney

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7
Q

ATP required for gluconeogenesis is supplied by what?

A

Beta - oxidation of fatty acids

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8
Q

How are Gluconeogenesis & Glycolysis related?

A

They share 7 reversible steps and enzymes. There are 3 irreversible reactions of glycolysis bypassed by gluconeogenesis

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9
Q

Explain the net equation of gluconeogenesis.

A

The synthesis of one mol glucose from 2 moles pyruvate requires 2NADH, 4ATP, 2GTP

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10
Q

This is has bypass reactions that circumvent highly exergonic glycolytic processes.

A

Gluconeogenic pathway

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11
Q

What are the three (3) irreversible steps in glycolysis?

A

(1) Phosphorylation of glucose by hexokinase: ( glucose —> glucose-6-phosphate)
(2) 2Phosphorylation of fructose-6-phosphate by PFK (fructose-6-phosphate —-> fructose-1,6-bisphosphate)
(3) Hydrolysis of PEP to pyruvate coupled to phosphorylation of ADP to ATP by pyruvate kinase (PEP —-> pyruvate)

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12
Q

What happens in step 01 of gluconeogenesis?

A

The carboxylation of pyruvate to oxaloacetate from 3 C’s to 4 C’s/

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12
Q

Oxaloacetate is a what?

A

keto dicarboxylic acid

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13
Q

What is the bypass enzyme for the carboxylation of pyruvate to oxaloacetate from 3 C’s to 4 C’s?

A

pyruvate carboxylase

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14
Q

What is the location for the carboxylation of pyruvate to oxaloacetate from 3 C’s to 4 C’s?

A

mitochondria

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14
Q

What does the carboxylation of pyruvate to oxaloacetate from 3 C’s to 4 C’s need?

A

ATP, BIOTIN*, and CO2,. * Pyruvate carboxylase requires Acetyl CoA as positive modulator or activator

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15
Q

This exist in both cytosol & mitochondria and catalyzes the decarboxylation and phosphorylation of oxaloacetate to PEP with the use of GTP

A

PEP carboxykinase

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16
Q

What happens in step 02 of gluconeogenesis?

A

Oxaloacetate undergoes phosphorylation and carboxylation to form PEP with the use of GTP>

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17
Q

What are the two (2) routes by which PEP can be synthesized?

A

when pyruvate or lactate is the precursor

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18
Q

Mitochondrial membrane has no transporter for oxaloacetate; it is shuttled by ________.

18
Q

This is the mitochondrial1st regulatory enzyme in gluconeogenesis; requires ACETYL CoA as + allosteric effector

A

Pyruvate carboxylase

19
This could be cytosolic or mitochondrial Mg+2 dependent & requires GTP as P grp donor
PEP carboxykinase
20
This catalyzes the irreversible hydrolysis of C1 phosphate.
Mg2+ dependent fructose 1 biphosphatase base
21
Where is Fructose-1,6-bisphosphatase present?
liver, kidney, and skeletal muscle
21
This enzyme is located in the cytosol and dephosphorylates fructose 1,6-bisphosphate to give fructose 6-phosphate. The presence of this enzyme determines if a tissue is capable of synthesizing glucose or glycogen from triose phosphates
Fructose-1,6-bisphosphatase
22
Where is Fructose-1,6-bisphosphatase absent?
heart and smooth muscle
23
Fructose-1,6-bisphosphatase can allosterically inhibited by?
AMP
24
Fructose-1,6-bisphosphatase can allosterically stimulated by?
citrate
25
How many mole is generated from Fructose-1,6-bisphosphatase?
16.3 kJ/mol
26
This enzyme catalyzes the irreversible hydrolysis. It is found in the liver and kidney (lumenal side of ER).
Mg2+ activated glucose 6 phosphatase
27
This enzyme is located in the cytosol and dephosphorylates glucose 6-P to give glucose
glucose 6 phosphatase
28
Presence of this enzyme in the _________________makes gluconeogenesis possible
ER of liver and kidney cells
29
Glucose 6 phosphatase is found only?
Enzyme is found only in liver, kidney & small intestine
30
Why do muscles and brain DO NOT undergo gluconeogenesis
Muscles and brain DO NOT undergo gluconeogenesis because the enzyme is absent
31
How much moles is generated by glucose 6 phosphatase?
13.8 kJ/mol
32
This hormone is secreted in response to increased blood glucose enhances the synthesis of key enzymes in glycolysis.
Insulin
33
It hormones responsive to a decrease in blood glucose, inhibit glycolysis & stimulate gluconeogenesis in the liver by increasing cAMP (2o messenger).
Glucagon & Epinephrine
34
During the Cori Cycle, glucose in the muscle is used to form __________.
Pyruvate
35
During the Cori Cycle, in anaerobic metabolism, pyruvate is converted to _________.
Lactate
36
Explain the Cori Cycle.
(1) Lactate goes to the bloodstream then to the liver (2) Lactate is converted to pyruvate (3) Pyruvate is converted to glucose-6P (gluconeogenesis) (4) Glucose-6P is hydrolyzed to glucose and released to the bloodstream then to the muscles
36
What is the importance of the Cori Cycle?
(1) Cori cycle prevents lactic acidosis (excessive accumulation of lactate) in muscle under anaerobic conditions. (2) This cycle is also important for production of energy molecule (ATP) during muscle activity, as muscles get deprived of energy due to insufficient glucose.
37
These are are amino acids that cannot provide carbon sources for synthesis of glucose, because they will give rise to acetoacetyl CoA or acetyl CoA.
Ketogenic
37
Acetyl CoA is oxidized to ________in Krebs.
2CO2
38
These are amino acids that give rise to pyruvate or Krebs intermediates which becomes oxaloacetate which can be converted to glucose.
Glucogenic
39
These are reactions that lead to net synthesis of TCA cycle intermediates, reactions that will replenish Krebs intermediates.
Anaplerotic reactions
40
These are reactions that lead to the net synthesis of Krebs intermediates. They support gluconeogenesis because they provide for net synthesis of oxaloacetate
Anaplerotic reactions (anaplerosis)
41
All amino acids except______________ can provide C for net synthesis of glucose by gluconeogenesis.
Leu and Lys
41
End product of Lys metabolism:
Acetyl CoA
42
End product of Leu metabolism:
Acetoacetate and Acetyl CoA
43
During fasting glucose or glycogen forms pyruvate. The pyruvate undergoes transamination to alanine
Glucose-Alanine Cycle
44
Explain the glucose-alanine cycle
In the fasting state, alanine accumulates in the cell and the excess is transferred to the liver where it is reconverted back to pyruvate. This reformed pyruvate can therefore undergo gluconeogenesis in the liver.
45
When muscles degrade amino acids from proteins during starvation, what is transferred?
ammonium is generated which is transferred to pyruvate generating alanine.
46
What does alanine do?
(1) brings the ammonium group to the liver and converts it to urea (2) pyruvate from alanine is used to make glucose for energy