Gluconeogenesis Overview and Importance

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Questions and Answers

What is the primary purpose of gluconeogenesis?

To break down glycogen into glucose

To synthesize glucose from non-carbohydrate sources (correct)

To transport glucose to the brain

To convert glucose into lactic acid

Which enzyme is responsible for the conversion of pyruvate to oxaloacetate in gluconeogenesis?

Fructose 1,6-bisphosphatase

Malate dehydrogenase

Pyruvate carboxylase (correct)

Phosphoenol pyruvate carboxykinase

During fasting, where does the majority of gluconeogenesis occur in the body?

In the skin

In the lungs

In the heart

In the liver (correct)

Which of the following is NOT a substrate for gluconeogenesis?

Fructose Signup and view all the answers

Which step in gluconeogenesis is specifically catalyzed by fructose 1,6-bisphosphatase?

Dephosphorylation of fructose 1,6-bisphosphate Signup and view all the answers

What is the cellular location where oxidative decarboxylation of pyruvate to oxaloacetate occurs?

Mitochondria Signup and view all the answers

Which of the following statements about gluconeogenesis is false?

It uses the same enzymes as glycolysis throughout. Signup and view all the answers

What is the initial molecule that enters gluconeogenesis after being transported to the mitochondria?

Pyruvate Signup and view all the answers

What is the main substance that is converted into glucose-6-phosphate during gluconeogenesis?

Fructose 1,6-bisphosphate Signup and view all the answers

Which enzyme is primarily responsible for converting pyruvate into oxaloacetate?

Pyruvate carboxylase Signup and view all the answers

What is the energy cost associated with converting 2 molecules of pyruvate to glucose?

6 ATP and 2 NADH+H+ Signup and view all the answers

Which regulatory hormone stimulates gluconeogenesis by inducing the synthesis of key enzymes?

Cortisol Signup and view all the answers

Which of the following substances is NOT considered a gluconeogenic precursor?

Fructose-6-phosphate Signup and view all the answers

What effect does insulin have on gluconeogenesis?

It inhibits gluconeogenesis. Signup and view all the answers

During gluconeogenesis, what is glycerol converted into before entering the common pathway?

Dihydroxy acetone phosphate Signup and view all the answers

What is the role of glucagon in the regulation of gluconeogenesis?

It stimulates gluconeogenesis by promoting enzyme phosphorylation. Signup and view all the answers

Study Notes

Gluconeogenesis Definition

Gluconeogenesis is the synthesis of glucose or glycogen from non-carbohydrate sources
These sources include lactic acid, pyruvic acid, propionic acid, glycerol, and amino acids

Gluconeogenesis Site

Organ site: 90% in the liver and 10% in the kidney
Cellular site: cytoplasm and mitochondria

Importance of Gluconeogenesis

Provides blood with glucose during fasting (more than 18 hours) when glycogen stores are depleted
The only source of energy for nervous tissue, red blood cells (RBCs), and skeletal muscles during exercise.
Precursor for milk sugar (lactose) in mammary gland
Clears the blood of waste products like lactic acid produced in skeletal muscles and RBCs

Gluconeogenesis Steps

Primarily the reversal of glycolysis, except for 3 irreversible kinases.
These irreversible kinases are bypassed by specific enzymes.
Key enzymes involved in gluconeogenesis include:
- Pyruvate carboxylase (mitochondrial)
- Phosphoenolpyruvate carboxykinase
- Fructose 1,6-bisphosphatase
- Glucose-6-phosphatase

Conversion of Pyruvate to Phosphoenolpyruvate

Pyruvate must be transported from the mitochondria to the cytoplasm.
The process involves Pyruvate carboxylase and Phosphoenolpyruvate carboxykinase
Pyruvate → Oxaloacetate → Malate → Oxaloacetate → phosphoenolpyruvate

Conversion of Fructose 1,6-Bisphosphate to Fructose-6-Phosphate

Catalyzed by Fructose 1,6-bisphosphatase

Conversion of Glucose-6-Phosphate to Glucose

Catalyzed by Glucose-6-phosphatase

Gluconeogenic Substances

Gluconeogenic amino acids
Pyruvate and lactate
Propionate (occurs only in ruminants)
- Propionic acid is converted to succinyl CoA
Glycerol
- Derived from lipids in adipose tissue during fasting
- Converted to glycerol-3-phosphate and then dihydroxyacetone phosphate.

Energy Cost of Gluconeogenesis

Converting 2 molecules of pyruvate to glucose requires:
- 6 ATP molecules
- 2 NADH+H⁺

Regulation of Gluconeogenesis

Gluconeogenesis and glycolysis are coordinated. When one is active, the other is inhibited
Key regulatory enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase
These enzymes are regulated by changes in enzyme synthesis, covalent modification, and allosteric regulation.

Regulation of Enzyme Synthesis

Glucocorticoids (cortisol) stimulate gluconeogenesis
- Increase synthesis of key gluconeogenesis enzymes
- Increase protein catabolism to provide amino acids
Insulin inhibits gluconeogenesis by suppressing enzyme synthesis

Covalent Modification

Glucagon and epinephrine stimulate gluconeogenesis by phosphorylating/activating key enzymes like pyruvate kinase (making it inactive hence inhibiting glycolysis)
This inhibits glycolysis and stimulates gluconeogenesis

Allosteric Regulation

Acetyl CoA is an allosteric activator of pyruvate carboxylase.
Derived from fatty acid (FA) oxidation
Stimulates gluconeogenesis by providing Acetyl CoA which activates pyruvate carboxylase.
Also needs ATP for pyruvate carboxylase and phosphoenol pyruvate carboxykinase.

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Description

Explore the process of gluconeogenesis, its definition, sites of occurrence, and its critical role in maintaining blood glucose levels during fasting and exercise. This quiz covers the key steps and enzymes involved in gluconeogenesis and its significance in energy metabolism.