Carbohydrate Metabolism II Quiz

Carbohydrate Metabolism II

• Carbohydrate metabolism encompasses digestion, absorption, catabolism (glycolysis, pentose-phosphate pathway, glycogenolysis), and anabolism (gluconeogenesis, glycogenesis). Cellular respiration, specifically the citric acid cycle, is also crucial.

Gluconeogenesis

• Gluconeogenesis forms glucose from non-carbohydrate precursors like 3-carbon compounds (pyruvate, lactate, glycerol) and glucogenic amino acids.
• Primarily occurs in liver cells, with some activity in the kidneys.

Glucogenic Amino Acids

• Eighteen of the twenty amino acids are glucogenic.
• Leucine and Lysine are the two non-glucogenic amino acids.
• Glucogenic amino acids can be converted to citric acid cycle intermediates.

Gluconeogenesis - Bypass Reactions

• Gluconeogenesis is a reciprocal process to glycolysis.
• It bypasses three irreversible steps in glycolysis.
• The first bypass converts pyruvate to phosphoenolpyruvate through oxaloacetate.

1st Bypass

• Oxaloacetate is transported out of the mitochondria as malate.
• Malate is converted back to oxaloacetate.
• Oxaloacetate is further converted into phosphoenolpyruvate, a critical intermediate in gluconeogenesis.
• NADH is produced during this conversion, contributing to subsequent gluconeogenesis.

2nd and 3rd Bypass Reactions

• The second bypass involves converting fructose-1,6-bisphosphate to fructose-6-phosphate via fructose-1,6-bisphosphatase-1 enzyme.
• The third bypass converts glucose-6-phosphate to glucose via glucose-6-phosphatase.

How is Gluconeogenesis Regulated?

• Acetyl-CoA is a positive modulator of pyruvate carboxylase, pushing the pathway towards gluconeogenesis.
• It's a negative regulator of pyruvate dehydrogenase, which is essential for glycolysis.

Fructose 2,6-bisphosphate

• Fructose 2,6-bisphosphate is a potent regulator affecting both glycolysis and gluconeogenesis.
• High levels stimulate phosphofructokinase and inhibit fructose-1,6-bisphosphatase in favor of glycolysis. Low levels favor gluconeogenesis.
• Glucagon decreases F-2,6-BP levels through fructose-2,6-bisphosphatase enzyme, stimulating gluconeogenesis.

Hormonal Regulation

• Insulin inhibits gluconeogenesis when blood glucose levels are high.
• Glucagon stimulates gluconeogenesis when blood glucose levels are low.
• Cortisol and epinephrine promote gluconeogenesis during stress, ensuring a constant glucose supply for energy.

Pentose Phosphate Pathway (PPP)

• The PPP operates in parallel with glycolysis.
• It has two phases: oxidative and non-oxidative.
• G6PD is a rate-limiting step.
• Important products of the oxidative phase are ribose-5-phosphate and NADPH.

How is PPP Regulated?

• Regulation depends on the cell's needs and NADP+ concentration.
• When nucleotides need to be synthesized or cells are dividing, the PPP is favoured.
• When NADPH is required (e.g. for fatty acid, cholesterol, and steroid synthesis), the PPP is also favoured.

Glycogen Metabolism

• Glycogenesis involves glycogen synthesis.
• Glycogenolysis involves glycogen breakdown.
• Insulin promotes glycogen synthesis.
• Glucagon promotes glycogen breakdown.

Organs and Glycogen

• The liver and muscle are key organs for glycogen metabolism.
• Glycogenesis occurs during the 'fed' state when blood glucose levels are high.
• Insulin regulates blood glucose levels partially by influencing glycogen.
• Muscle glycogen is used for local energy during exercise whereas liver glycogen releases glucose into the bloodstream.

Glycogenolysis

• Glycogenolysis involves glycogen breakdown, releasing glucose units into the bloodstream.

Carbohydrate Metabolic Diseases

• Diabetes Mellitus (Type I and Type II) are examples of carbohydrate metabolic disorders.

Other Examples

• Lactose intolerance results from low lactase levels due to genetic deficiency or intestinal injury.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency impacts NADPH production, leaving cells vulnerable to oxidative damage.