Regulation of carbohydrate metabolism Flashcards
What is the glycolytic pathway?
The glycolytic pathway, also known as glycolysis, is a metabolic pathway that occurs in all tissues of the body. It is particularly important for energy production in the brain, red blood cells, and contracting skeletal muscle. Glycolysis involves the breakdown of glucose into pyruvate, generating ATP and NADH in the process.
What is gluconeogenesis?
Gluconeogenesis is the process of de novo synthesis of glucose from non-carbohydrate precursors, such as lactate, amino acids, and glycerol. It occurs primarily in the liver (and kidneys) and serves to maintain blood glucose levels during fasting, starvation, or when glycogen reserves are depleted. Gluconeogenesis is not a simple reversal of glycolysis and requires unique enzymes to overcome energetically unfavorable reactions.
How is the glycolytic pathway regulated?
The glycolytic pathway is regulated through coordinated control with gluconeogenesis. In mammals, gluconeogenesis primarily takes place in the liver to provide glucose for other tissues. Certain reactions in glycolysis are essentially irreversible, including those catalyzed by hexokinase, PFK-1 (phosphofructokinase-1), and pyruvate kinase. Gluconeogenesis uses bypass reactions, such as glucose 6-phosphatase, fructose 1,6-bisphosphatase-1, PEP carboxykinase, and pyruvate carboxylase, to overcome these irreversible steps.
What is gluconeogenesis?
Gluconeogenesis is the process of synthesizing glucose from non-carbohydrate sources. It requires a source of energy, which is provided by the metabolism of fatty acids released from adipose tissue, and a source of carbon, which is provided by lactate, amino acids, or glycerol released from triglycerides in adipose tissue.
What are the irreversible steps in glycolysis and how are they overcome in gluconeogenesis?
The irreversible steps in glycolysis are overcome in gluconeogenesis by the expression of specific gluconeogenic enzymes. These enzymes catalyze the reactions that bypass the irreversible steps of glycolysis, allowing for the synthesis of glucose. These bypass reactions are sites of regulation by hormones and are shown in red in the gluconeogenic pathway.
How is glycolysis regulated in relation to gluconeogenesis?
Glycolysis is regulated in coordination with gluconeogenesis. The enzyme phosphofructokinase-1 (PFK-1), a key regulatory enzyme in glycolysis, is subject to allosteric regulation by ATP, AMP, and H+. ATP inhibits PFK-1, indicating high energy levels, while AMP activates it, indicating low energy levels. This allosteric regulation ensures that glycolysis and gluconeogenesis are reciprocally regulated and coordinated with cellular energy needs.
What is the role of H+ ions in the regulation of PFK-1?
H+ ions, which increase during anoxia or anaerobic muscle contraction due to lactic acid production, inhibit PFK-1. This inhibition prevents cellular pH from falling too low and damaging the cellular machinery. In the heart, high AMP levels can overcome the inhibitory effect of H+, leading to cellular damage and chest pain experienced during heart attacks and angina.
How is PFK-1 regulated by nutrients?
PFK-1 is subject to allosteric regulation by fructose-6-phosphate, fructose-2,6-bisphosphate, and citrate. Fructose-6-phosphate and fructose-2,6-bisphosphate activate PFK-1, indicating high rates of glucose entry or glycogen breakdown. This stimulation of glycolysis allows for the utilization of glucose for energy production or fat synthesis. Citrate inhibits PFK-1 and signals TCA cycle overload or fatty acid oxidation, indicating the need to conserve glucose by inhibiting glycolysis.
What is the role of fructose 2,6-bisphosphate in PFK-1 regulation?
Fructose 2,6-bisphosphate is the most potent allosteric activator of PFK-1. It stimulates glycolysis and is a potent inhibitor of fructose-1,6-bisphosphatase. It acts solely to reinforce allosteric control on PFK-1 and is not involved in metabolic pathways.
What activates the production of fructose 2,6-bisphosphate (F-2,6-BP)?
Fructose 2,6-bisphosphate (F-2,6-BP) is activated by high levels of fructose-6-phosphate (F-6-P), indicating increased glucose concentrations and glycogen breakdown in muscle. It is also activated by AMP, which is increased during muscle contraction when ATP levels are low.
What inhibits the production of fructose 2,6-bisphosphate (F-2,6-BP)?
Fructose 2,6-bisphosphate (F-2,6-BP) production is inhibited by citrate, which indicates increased fatty acid oxidation and TCA cycle overload.
What are the factors that inhibit glycolysis at the PFK-1 checkpoint?
Glycolysis is inhibited by the presence of sufficient energy (ATP), fatty acid oxidation (citrate), and high levels of H+ ions (indicating high lactate levels).
What are the factors that activate glycolysis at the PFK-1 checkpoint?
Glycolysis is activated by low levels of energy (AMP) and high levels of glucose or its metabolites.
Why does the liver require additional control over the regulation of F-2,6-BP?
In the liver, glycolysis is inhibited because it primarily uses glucose produced via gluconeogenesis to maintain blood glucose levels. Glycogen breakdown is also utilized by the liver for glucose production. Therefore, the liver requires additional control to prevent excessive glycolysis.
What controls the activity of PFK-2 and F-2,6-BPase in the liver?
The activity of PFK-2 and F-2,6-BPase in the liver is controlled by the level of fructose-2,6-bisphosphate (F-2,6-BP), which is affected by hormones. Phosphorylation inhibits PFK-2 and stimulates F-2,6-BPase, leading to decreased levels of F-2,6-BP.
