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Block 1 - Week 1 > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

Gluconeogenesis

A
  • Metabolic pathway to make glucose from Amino Acids, Lactate, and Glycerol
  • Occurs when fasting: allows body to maintain glucose
  • Primarily occurs in Liver Cells; also occurs in the Epithelial Cells of the Kidney and Intestine
  • Occurs in the Cytoplasm, Endoplasmic Reticulum, and Mitochondria of the cells in these tissues
  • Makes Glucose from scratch
  • Main provider of blood glucose after 12h of fasting
  • Uses ATP to convert Pyruvate into Glucose (opposite of Glycolysis)
  • Similar to reverse Glycolysis; except there are 3 irreversible reactions that need to be bypassed
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2
Q

Where and how is glucose stored?

A

Glucose is stored in the Liver as Glycogen which are glucose molecules connected together

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3
Q

Why is it important to still have glucose when fasting?

A

Glucose is needed for the RBCs and the Brain when fasting

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4
Q

Glycogenolysis

A
  • In a fasting state, the liver will break down Glycogen into individual Glucose molecules
  • Maintains glucose levels for 12-24 hours of fasting
  • Glycogen stores are finite
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5
Q

What are the main sources of Pyruvate in Gluconeogenesis?

A
  • Lactate (Biproduct of Anaerobic Respiration in RBCs and exercising muscle cells)
  • Amino Acids (All except Leucine and Lysine) –> Fasting for a long time breaks down Amino Acids from Skeletal Muscle –> Main Amino Acid used is Alanine
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6
Q

How is Lactate converted to Pyruvate?

A
  • Via Enzyme Lactate Dehydrogenase

- This produces 1 NADH in the process

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7
Q

How is Alanine converted to Pyruvate?

A
  • Via Enzyme Alanine Transaminase
  • During this reaction Alpha Ketoglutarate is also converted to Glutamate
  • This reaction requires Pyridoxine (Vitamin B6)
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8
Q

How are fats broken down during fasting to create ATP?

A
  • Low insulin and presence of Epinephrine and ACTH cause Adipocytes (Fat Cells) to stimulate Hormone Sensitive Lipase (HSL), an Enzyme that breaks down Triacylglycerides to 3 Fatty Acids and Glycerol
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9
Q

What happens with the pancreas during fasting?

A

Pancreatic a-cells sense decrease in glucose –> Release Glucagon –> Triggers Glycogenolysis: conversion of stored glycogen in the liver to glucose, which can be released into the bloodstream

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10
Q

Beta Oxidation

A

Breakdown of Fatty Acids to Acetyl-CoA and ATP in the Hepatocyte Mitochondria

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11
Q

After Triglyceride breakdown, what is Glycerol used for?

A

Glycerol is used to make Glucose in Gluconeogenesis

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12
Q

What molecules will be used in Gluconeogenesis to make Glucose?

A
  • Glycerol (From Triglycerides)
  • Lactate (Biproduct of Anaerobic Respiration in RBCs and exercising muscle cells)
  • All Amino Acids (Except Leucine and Lysine)
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13
Q

First step of Gluconeogenesis

A
  • Pyruvate –> Enzyme Pyruvate Carboxylase –> Oxaloacetate –> Malate Shuttle –> Enzyme PEPCK –> Phosphoenolpyruvate (PEP)
  • Note: In Glycolysis: PEP –> Pyruvate Kinase –> Pyruvate (irreversible)
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14
Q

What Cofactors do Carboxylase Enzymes need?

A
  • ATP (From Fatty Acid Oxidation)
  • Biotin
  • CO2
  • Carboxylase Enzymes need their ABCs
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15
Q

What enhances Carboxylase activity?

A
  • Acetyl-CoA (Made during Fatty Acid Oxidation)
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16
Q

What is the Malate Shuttle?

A
  1. ) Oxaloacetate can’t exit the Mitochondria to the Cytoplasm
  2. ) Malate Dehydrogenase (MDH) converts Oxaloacetate into Malate which can leave the Mitochondria into the Cytoplasm
  3. ) MDH then converts Malate back to Oxaloacetate
17
Q

What promotes the PEPCK Enzyme?

A

Stress Hormones:

  1. ) Glucagon
  2. ) Epinephrine
  3. ) Cortisol

This speeds up Gluconeogenesis

18
Q

Second step of Gluconeogenesis

A
  • Multiple reversible reactions (similar to Glycolysis) –> Ultimately converted to DHAP
  • Glycerol from HSL Activity can also be used to make DHAP
19
Q

How is Glycerol converted to DHAP?

A

Glycerol –> (Glycerol Kinase, uses ATP) –> G3P –> (G3P Dehydrogenase) –> DHAP

20
Q

Third step of Gluconeogenesis

A

DHAP –> (Aldolase) –> Fructose-1-6-Bisphosphate

21
Q

Fourth step of Gluconeogenesis

A

Fructose-1-6-Bisphosphate –> (Fructose-1-6-Bisphosphatase) –> Fructose-6-Phosphate

RATE LIMITING STEP OF GLUCONEOGENESIS

22
Q

What is the rate limiting step of Gluconeogenesis?

A

Fructose-1-6-Bisphosphate –> (Fructose-1-6-Bisphosphatase) –> Fructose-6-Phosphate

23
Q

What enhances the Enzyme Fructose-1-6-Bisphosphatase?

A
  • ATP Enhances (Fatty acids burned in the liver yiel lots of ATP; liver needs energy to carry out Gluconeogenesis)
  • Glucagon Enhances
  • Insulin Inhibits
24
Q

Fifth step of Gluconeogenesis

A

Fructose-6-Phosphate –> (Isomerase) –> Glucose-6-Phosphate

Note: A phosphate keeps the glucose in the cell; must remove the phosphate in order to let the glucose leave the cell and enter the bloodstream

25
Q

Sixth step of Gluconeogenesis

A

Glucose-6-Phosphate –> (Glucose-6-Phosphatase) –> Glucose

Note: Now that the phosphate group has been removed the glucose can exit the cell and enter the bloodstream

26
Q

How does alcohol relate to Gluconeogenesis?

A
  • Alcohol (Ethanol) is processed in Liver Cells
  • Results in buildup of NADH and ATP in the Cytoplasm
  • Increased NADH levels signal the Lactic/Malate/G3P Dehydrogenases Enzymes in Gluconeogenesis to reverse the direction and go from Pyruvate to Lactate, from Oxaloacetate to Malate, and DAHP to G3P
  • Increase in ATP –> decreases Fatty Acid Beta Oxidation –> Causes accumulation of Fat in the Liver
  • All of the above impairs Gluconeogenesis –> Leads to Chronic Low Blood Sugar when Fasting
27
Q

What are the 3 irreversible reaction Enzymes in Glycolysis and what enzymes in Gluconeogenesis overcome these?

A
  1. ) Pyruvate Kinase (Glycolysis), overcome by Pyruvate Carboxylase, Malate Dehydrogenase, and PEPCK in (Gluconeogenesis)
  2. ) PFK1 (Glycoylsis), overcome by Fructose-1-6-Bisphosphate in (Gluconeogenesis)
  3. ) Hexokinase (Glycolysis), overcome by Glucose-6-Phosphatase in (Gluconeogenesis)

Block 1 - Week 1 (6 decks)

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