Metabolism Lecture 3 & 4 - Gluconeogenesis & TCA/CAC Flashcards

1
Q

What are the 3 fates of Acetyl CoA?

A
  1. CAC
  2. Ketone Bodies
  3. Fatty Acids/Sterols
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2
Q

What are 3 ways Acetyl Co A is formed?

A
  1. Pyruvate oxidation
  2. Fatty Acid Beta-oxidation
  3. Amino Acid Deamination & oxidation
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3
Q

If the following enzymes were deficient, the production of what would be hindered? What kind of deficiency is this?

  1. Thamine (TPP, B1)
  2. Riboflavin (FAD, B2)
  3. Niacin (NAD, B3)
A

Pyruvate Dehydrogenase Deficiency

PDH complex!

Could not convert pyruvate to Acetyl Co A

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4
Q

What is the most common form of Pyruvate Dehydrogenase Deficiency?

What accumulates in this deficiency? (3)

A

Mutations in E1

  • X linked dominant

(other forms are autosomal recessive)

  1. Pyruvate
  2. Lactate
  3. Alanine
  • lead to CHRONIC LACTIC ACIDOSIS
  • Some patients have been treated with dichloroacetate, an inhibitor of the protein kinase subunit of pyruvate dehydrogenase complex.
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5
Q

Transamination of alanine, Carboxylation of OAA, and reduction of lactate all produce what?

A

PYRUVATE!

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6
Q

Each cycle of CAC generates how much ATP?

Describe the contribution of the following:

  1. NADH
  2. FADHS
  3. GTP
A
  1. NADH = 3 (@2.5) = 7.5
  2. FADH2 = 1 (@1.5) = 1.5
  3. 1 GTP = 1 ATP

TOTAL = 10 ATP!!! In 1 cycle of CAC

(but each glucose produces 2 acetyl Co A’s, thus 20 ATP total)

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7
Q

What is fine control of CAC? (state the 2 enzymes involved)

Course Control? (6)

A
  1. Allosteric Regulation of:

a) Isocitrate Dehydrogenase
b ) a-Ketoglutarate Dehydrogenase

2.MAJOR mechanism of regulation

a) ADP, NADH, FADH2
b) Acetyl Co A
c) OAA

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8
Q

How do the following affect the CAC:

  1. Higher concentration of ADP and Calcium
  2. Higher concentration of ATP, GTP, and NADH
A
  1. STIMULATE CAC **(low energy)
    - Calcium & ADP act on a-ketoglutarate dehydrogenase)
    - ADP acts on isocitrate dehydrogenase
  2. INHIBIT CAC***
    - NADH, GTP and Succinyl Co A both act on a-ketoglutarate dehydrogenase
    - ATP acts on Isocitrate Dehydrogenase
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9
Q

How can the citric acid cycle intermediates be replenished by ANAPLDROTIC reactions?

What can replenish:

  1. OAA
  2. Fumarate
  3. Succinyl Co A
  4. a-ketoglutarate
A
  1. Aspartate
  2. Amino Acids (aspartate, phenylalanine, tyrosine)
  3. Propionyl Co A (via valine & isoleucine)
  4. Glutamate (via amino acids)
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10
Q

What does gluconeogensis use to form glucose? (3)

A

NON - carbohydrate carbon substrates

  1. Pyruvate
  2. Glycerol
  3. Glucogenic Amino Acids
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11
Q

What stimulates Gluconeogenesis?

What does it require?

What two step process is required to get PEP?(activated form of pyruvate)

What enzyme is needed to convert OAA to PEP?

A
  1. Low blood glucose
    mainly in the LIVER, some in the kidney
  2. ATP
  3. Malate shuttle to convert OAA to malate–> to bring it out of mitochondria

and then malate back to OAA
- this is decarboxylated and converted to PEP

  1. Enzyme PEP Carboxy Kinase
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12
Q

What 2 major factors are important to initiate Gbuconeogensis in order for Pyruvate Carboxylase to convert Pyruvate to OAA to be converted later into PEP?

A
  1. Bicarbonate
  2. Cofactor Biotin
    - requires the use of ATP
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13
Q

What is the difference between the Cori Cycle & the Alanine cycle?

A
  1. Cori
    - conversion of lactate to glucose
    (RBC + muscle)
  • require 6 ATP and 2 Lactate to form 1 glucose
  1. Alanine Cycle: (muscle)
    - conversion of alanine to glucose
    - occurs in LIVER
    - AMMONIA is a secondary by product
    - thus it requires 6 ATP for cycle and 4 ATP for Ureagenesis

TOTAL 10 ATP

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14
Q

What is the main requirement for Gluconegensis (from all precursors)?

Gluconeogenesis from what specific precursor requires ADDITIONAL ATP?

What is the major source of ATP for gluconeogenesis during an overnight fast?

A
  1. ATP!
  2. Amino Acids (alanine cycle)
  3. Oxidation of fatty acids!
    - not from lactate or alanine
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15
Q

WHat 4 enzymes are required to reverse the 3 irreversible steps of glycolysis?

Where is each found?

Which enzyme is found in the ER?

A
  1. Mitochondrial: Pyruvate Carboxylase

Cytoplasmic:

  1. PEP Carboxy kinase
  2. Fructose - 1,6 - BisPhosphotase
  3. Cytoplasmic (enzyme in ER)
    Glucose - 6 - Phosphotase

(which is why gluconeogenesis only occurs in the liver)

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16
Q

What are the symptoms in Pyruvate Carboxylase deficiency?

What accumulates?

A
  1. Failure to thrive, developmental delay, recurrent seizures, metabolic acidosis
  2. Pyruvate accumulates in the plasma
    - converted to LACTATE
    - elevated LACTIC ACID
  3. Pyruvate
  4. Lactate
  5. ALANINE in serum
17
Q

What type of disease if a Glucose 6 - Phosphotase Deficiency?

What cannot be converted?

Why is one of the main symptoms hepatomegaly?

What is elevated?

What 2 processes are hindered?

A
  1. Metabolic - Autosomal Recessive
    GLYCOGEN STORAGE DISEASE!!
    (Type I GSD or Von GIerke Disease)
  2. G - 6 - P cannot be converted to Glucose
  3. Poor tolerance to fasting, growth retardation, and HEPATOMEGALY
    - due to accumulation of GLYCOGEN & FAT in liver
  4. Elevated Serum Uric Acid & Lactate
  5. Gluconeogenesis & Glycogenolysis
18
Q

How can ethanol metabolism lead to hypoglycemia?

What decreases & what increases? (4 total)

Increased NADH is directly linked to increased production of what?

A

HIGH NADH associated with ethanol

  • NADH converted pyruvate to lactate and OAA to malate

Increases:

  1. Lactate
  2. Malate

Decreases:

  1. Pyruvate
  2. OAA
    - thus Hypoglycemia results since no GLUCONEOGENIC precursors available to make GLUCOSE

INCREASED NADH = INCREASED LACTATE formation