Gluconeogenesis: Conversion Reactions

Study Notes

Gluconeogenesis is the reverse of glycolysis, and the reaction from F6P to G-6-P is catalyzed by the same enzyme, phosphoglucose isomerase.
The reaction from G6P to glucose and Pi is the reverse of the reaction catalyzed by glucokinase and hexokinase during glycolysis, but in gluconeogenesis, it is catalyzed by glucose-6-phosphatase, which is present only in gluconeogenic tissues.
Gluconeogenesis and glycolysis are reciprocally regulated.

Insulin stimulates glycolysis, while glucagon stimulates gluconeogenesis.
A high AMP concentration indicates a low energy charge, signaling the need for ATP, whereas high ATP and citrate concentrations indicate a high energy charge and abundant intermediates.

The stoichiometry of gluconeogenesis is: 2pyruvate + 4ATP + 2GTP + 2NADH + 6H2O → glucose + 4ADP + 2GDP + 6Pi + 2NAD+ + 2H+.
The Gibbs free energy (ΔG°’) is -9kcal mol-1, which is the reverse of glycolysis with a ΔG°’ of 20kcal mol-1.

The pentose phosphate pathway provides a source of reduced NADPH for reductive biosynthesis, a source of ribose-5-phosphate for nucleic acid biosynthesis, and a route for the conversion of pentoses to fructose-6-phosphate.
The pathway is most active in erythrocytes, liver, mammary gland, adipose tissue, and adrenal cortex.
The enzymes of this pathway are located in the cytoplasm.

The oxidative phase is irreversible and regulated by glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by NADPH and activated by glucose-6-phosphate and GSSG.
A high CHO diet triggers the synthesis of G6PD and phosphogluconate dehydrogenase.

Anabolism is the process of building complex molecules from simpler ones, requiring energy from ATP.
Some cells have specific nutrient requirements, and certain compounds like vitamins, amino acids, and microorganisms cannot be synthesized and must be supplied in the diet or media.

Carbohydrate digestion involves the breakdown of carbohydrates into glucose, which is the major metabolic fuel of mammals, except ruminants.
Glucose is converted to pyruvate through glycolysis, which can occur aerobically or anaerobically.
Aerobic glycolysis produces pyruvate, which is oxidized to Acetyl Co-A, entering the Kreb's cycle, while anaerobic glycolysis produces lactate.
Glycolysis is central in generating both energy and metabolic intermediates.

Glycolysis is the breakdown of glucose into 2 molecules of pyruvic acid, producing 2 ATP molecules.
The pathway occurs in the cytoplasm and can function either aerobically or anaerobically.
All carbohydrates to be catabolized must enter the glycolytic pathway.
Glycolysis is regulated by three irreversible kinase reactions: hexokinase or glucokinase, phosphofructokinase, and pyruvate kinase.

Under anaerobic conditions, pyruvate is converted to lactate, which is important in red blood cells, parts of the retina, and skeletal muscle cells during strenuous exercise.
Lactate fermentation is reversible, allowing pyruvate to be regenerated in alternative metabolism.
Lactate dehydrogenase (LDH) has multiple forms, including the M and H forms, which are present in different tissues and have different functions.