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Biochemistry > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

Under what state does gluconeogenesis occur?

A

Fasting state when blood glucose levels are low

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2
Q

Name the 4 precursors of gluconeogenesis

A

Lactate/pyruvate, Amino acids, Glycerol, Propionyly CoA

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3
Q

What is gluconeogenesis?

A

The synthesis of new glucose molecules. Gluconeogenesis meets the needs of the body for glucose when sufficient carbohydrate is not available from the diet or glycogen reserves.

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4
Q

How many lactate molecules produces 1 glucose?

A

2

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5
Q

When lactate converts to glucose, how many ATP molecules are produced?

A

6

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6
Q

Which key enzyme in lactate to glucose converts pyruvate to OAA and where does it take place?

A

Pyruvate carboxylase
Takes place in the mitochondrial matrix

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7
Q

Which key enzyme in lactate to glucose converts OAA to phosphoenolpyruvate and where does it take place?

A

Phosphoenolpyruvate carboxylase (PEPCK)
Takes place in the cytosol

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8
Q

Which key enzyme in lactate to glucose converts Fructose-1,6-bisphophate to Fructose-6-phosphate and where does it take place?

A

Fructose-1,6-bisphosphatase
Takes place in the cytosol

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9
Q

Which key enzyme in lactate to glucose converts Glucose-6-phosphate to Glucose and where does this take place?

A

Glucose-6-phosphatase and takes place in the SER

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10
Q

Why is gluconeogenesis not just the reverse of glycolysis?

A

Because it uses 3 different enzymes in its pathway that are different from the enzymes in glycolysis (at the irreversible steps)
Three nonequilibrium reactions in glycolysis catalyzed by hexokinase,
phosphofructokinase, and pyruvate kinase are considered
thermodynamic barriers which prevent simple reversal of glycolysis
for glucose synthesis.

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11
Q

True or False: Biotin (Vit. B7) is a cofactor needed for gluconeogenesis and what molecule does it require to work properly?

A

True and ATP and CO2

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12
Q

Which of the following glycolytic enzymes is used in gluconeogenesis?
a) glucokinase
b) phosphofructokinase-1
c) aldolase B
d) Phosphoglycerate kinase
e) pyruvate kinase

A

D) phosphoglycerate kinase

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13
Q

What is the regulation of Pyruvate Carboxylase?

A

Beta Oxidation

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14
Q

Hypoglycemia is a defect in _____.

A

Beta oxidation

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15
Q

What is the allosteric activator of pyruvate carboxlase?

A

Acetyl CoA

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16
Q

How long can glycogen meet glucose demands before depleting?

A

<24hrs

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17
Q

What is glucose made from in a fasting state?

A

Non-carb precursors

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18
Q

Where does gluconeogenesis take place?

A

Liver and kidneys (and certain places in GIT)

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19
Q

How does propionate enter gluconeogenesis?

A

Via the citric acid cycle
-major precursor in ruminants

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20
Q
  • In non-ruminants, including humans, propionate arises from where?
A

1) the Beta -oxidation of odd-chain fatty acids that occur in ruminant lipids,
2) the oxidation of isoleucine and the side-chain of cholesterol

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21
Q

Explain how glucose is produced from glycerol and which organs does in occur in?

A

The triglyceride is broken down into glycerol and fatty acid by lipolysis. The glycerol is then converted to glycerol-3-phosphate which is then converted to dihydroxyacetone phosphate. DHAP can then be converted into Fructose-1,6-bisphosphate which is converted to Fructose-6-phosphate by the enzyme fructose-1,6-bisphosphatase and F-6-P gets converted to Glucose-6-P that enters the SER and is converted to Glucose

Solely as a substrate for gluconeogenesis in the liver and kidneys

22
Q

What are the three bypass reactions in gluconeogenesis?

A
  1. First bypass (Formation of Phosphoenolpyruvate from pyruvate)
  2. Second bypass (Formation of Fructose 6- phosphate from fructose 1,6-bisphosphate)
  3. Third bypass (Formation of Glucose by hydrolysis of glucose 6-phosphate)
23
Q

Is Biotin required for the conversion of pyruvate to OAA?

A

Yes

24
Q

Where does the GTP used in the conversion of OAA to PEP come from?

A

In liver and kidney, the reaction of succinate thiokinase in the citric acid cycle
produces GTP (rather than ATP as in other tissues), and this GTP is used for
the reaction of phosphoenolpyruvate carboxykinase.

25
Q

Where can Fructose-1,6-bisphosphatase be found?

A

Liver, kidney, Skeletal muscle

26
Q

Which pathway does insulin stimulate and which pathway does it inhibit?

A

Activates: Glycolysis
Inactivates: Gluconeogenesis

27
Q

Which enzymes does insulin stimulate?

A
  • Glucokinase
  • Phosphofructokinase,
  • Pyruvate kinase, and
  • F-2,6-BP (positive modifier of PFK-1).
28
Q

Which enzymes are stimulated by glucagon?

A
  • Phosphoenolpyruvate carboxykinase and
  • Fructose 1,6-bisphosphatase
29
Q

Which pathway does glucagon and epinephrine stimulate?

A

Gluconeogeneis (by increasing cAMP)

30
Q

Which pathway does glucagon and epinephrine Inhibit?

A

Glycolysis

31
Q

Which G-protein coupled pathway does glucagon and epinephrine stimulate and what happens to pyruvate kinase in the process?

A

Gs pathway and this in turn activates cAMP-dependent protein kinase, leading to the phosphorylation and inactivation of pyruvate kinase.

32
Q

What activates and inhibits pyruvate carboxylase?

A

ADP- inhibits
Acetyl Co-A- Activates

33
Q

What activates and inhibits Fructose-1,6-bisphosphatase?

A

Activator- citrate
Inhibitor- AMP, Fr-2,6-bisphosphatase

34
Q

What are Fr-1,6-bisphosphatatse & pyruvate carboxylase induced and repressed by?

A

Induced by: Glucocorticoids, glucagon, epinephrine
Repressed by: Insulin

35
Q

What is the clinical significance of Fr-1,6-bisphosphatatse & pyruvate carboxylase?

A

Activity increases in Diabetes Mellitus

36
Q

Explain how amino acids produce glucose

A

Proteins are broken down into amino acids. The amino acid + keto acid (alpha ketoglutarate) produces keto acid from the amino acid and glutamate from the alpha-ketoglutarate. the keto acid can then convert directly into pyruvate or it can be converted directly into acetyl Co-A or alpha-ketoglutarate or another molecule in the TCA cycle

These amino acids are called GLUCOGENIC amino acids

37
Q

Explain the Cori Cycle

A

In the muscle Glycogen gets converted to Glucose-1-P which then converts into G-6-P
G-6-P converts into Lactic acid and NAD+ is produced
The lactic acid enters the blood and goes into the liver
Once in the liver the lactic acid becomes pyruvate (by LDH) which is converted into G-6-P
G-6-P enters the SER and gets acted on by G-6-Phosphatase which converts it to Glucose. This glucose goes back into the blood and is converted back into G-6-P in the muscle

6ATP are used, 2 ATP produced

38
Q

Explain the Glucose-Alanine Cycle

A

The G-6-P from the Cori cycle that entered the muscle, is converted into pyruvate. The pyruvate joins with Glutamate. this reaction releases alpha-ketoglutarate and produces ALANINE.
Alanine then goes into the liver where it joins with alpha-ketoglutarate and converts back into pyruvate
Pyruvate then converts into G-6-P and G-6-P becomes Free glucose which goes into the blood.

39
Q

Which molecule is required for the conversion of OAA to PEP and what is released?

A

GTP and Co2

40
Q

What happens when pyruvate carboxylase is deficient?

A

Lactic acidosis because pyruvate accumulates and breaks down into lactate

41
Q

What is the rate limiting step of gluconeogenesis?

A

Frutose-1,6-bisphosphatase

42
Q

Which 2 amino acids cannot produce glucose?

A

Leucine and lysine

43
Q

Which 2 vitamin B complexes are needed for Propionyl CoA to glucose ?

A

Vitamin B7 (biotin) and B12

44
Q

Name the deficiency of vitamin B12

A

Methylmalonic acid in the blood and its excretion in urine

45
Q

Which enzyme converts Pyruvate + glutamate to alanine and alpha-ketoglutarate?

A

Alanine Transaminase

46
Q

What’s the importance of Alanine transaminase?

A

If there is liver cirrhosis this enzymes is tested

47
Q

What is produced when alcohol is consumed ?(alcohol converts to aldehyde—> alcohol dehydrogenase)

A

NADH (in high amounts)

48
Q

What is the consequence of too much NADH in alcohol metabolism?

A

Inhibits gluconeogenesis and excess NADH can inhibit fatty acid oxidation which provides ATP
-person in starvation is told not to drink alcohol

49
Q

Explain how Glucagon and epinephrine stimulate gluconeogenesis

A

Glucagon or epinephrine would bind onto the GCPR coupled receptor and activate Adenylyl cyclase. The AC causes ATP to break down into cAMP. This activated cAMP then stimulates PKA. This PKA then stimulate gluconeogenesis and also inhibits pyruvate kinase.

50
Q

Explain the biotin deficiency with raw egg and which enzyme is affected

A

Raw egg whites contain Avidin, a glycoprotein that strongly binds with biotin and prevents its absorption. As a result, the biotin-avidin complex is lost in the feces. Thus, the ingestion of large quantities of raw egg white over a long
period can result in a biotin deficiency. Cooking egg white denatures avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin.

Pyruvate Carboxylase

51
Q

Why is hypoglycemia seen more in premature/lo birth weight infants?

A

Due to little adipose tissue that they have. They won’t be able to effectively provide alternative means for glucose

Biochemistry (7 decks)

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