Phosphofructokinase-2 ( PFK-2) and fructose bisphosphatase-2 ( FBPase-2) are two domains of the same bifunctional enzyme.Function: Fructose 2,6-bisphosphate ( Fru-2,6-P2) stimulates glycolysis by increasing PFK-1 activity in states of high blood glucose concentrations.Phosphofructokinase-1 is the rate-limiting enzyme in glycolysis.įructose 2,6-bisphosphate ( feed-forward regulation) Glucagon ( fasting, only in the liver): indirect inhibition.Fructose 6-phosphate (feedback inhibition).Fructose 1,6-bisphosphate ( feed-forward stimulation).Insulin ( postprandial): indirect stimulation.Converts F6P to fructose 1,6-bisphosphate ( rate-limiting step of glycolysis).High K m (i.e., ↓ affinity compared to hexokinase) → sequestration of glucose in the liver only when blood glucose levels are high.Low K m (i.e., ↑ affinity compared to glucokinase) → sequestration of glucose in tissues even when blood glucose levels are low.All tissues, except liver and β-cells of the pancreas.In total, there is a net gain of 2 ATP per 1 molecule of glucose. In glycolysis, 2 ATP are invested to gain 4 ATP. The net reaction for glycolysis: glucose + 2 P i + 2 ADP + 2 NAD + → 2 pyruvate + 2 ATP + 2 NADH + 2 H + + 2 H2O Stimulated by fructose 1,6-bisphosphate.2 2-phosphoglycerate → 2 phosphoenolpyruvate (PEP) via enolase.2 3-phosphoglycerate → 2 2-phosphoglycerate via phosphoglycerate mutase.2 GAP → 2 1,3-biphosphoglycerate ( 1,3-BPG ).Fructose 1,6-bisphosphate → 2 glyceraldehyde 3- phosphate (GAP) via aldolase.G6P → fructose 6-phosphate ( F6P) via G6P isomerase.Glucokinase: in β-cells of the pancreas and liver tissue (inhibited by fructose 6-phosphate).Hexokinase: in all tissues (inhibited by G6P). Each glucose molecule produces 2 pyruvate molecules, which are composed of a 3-carbon skeleton. Glucose is composed of a 6-carbon skeleton (C 6H 12O 6). NADPH is required for the reduction of glutathione, an antioxidant preventing excess hydrogen peroxide and free radicals from damaging RBC membranes. Hemolytic anemia is caused by glucose-6-phosphate dehydrogenase deficiency, which results in insufficient production of NADPH. Ribose 5-phosphate is required for nucleotide synthesis, while NADPH is required for cholesterol synthesis, steroid synthesis, reduction of glutathione, and respiratory burst. The pentose phosphate pathway occurs exclusively in the cytosol and is highly active in the adrenal cortex, liver, and RBCs. Glucose can also be shunted to the pentose phosphate pathway (also known as the hexose monophosphate shunt), which is a metabolic pathway that generates nicotinamide adenine dinucleotide phosphate ( NADPH) and ribose 5-phosphate from glucose-6-phosphate. The metabolism of glucose is mainly controlled by hormones such as insulin, which stimulates glycolysis, and glucagon, which stimulates gluconeogenesis. Phosphofructokinase-1 is the rate-limiting enzyme for glycolysis, while fructose 1,6-bisphosphatase is the rate-limiting enzyme for gluconeogenesis. While the glycolytic pathway occurs in all cells, gluconeogenesis occurs almost exclusively in the liver. In gluconeogenesis, a process that ensures euglycemia during fasting, glucose is synthesized from noncarbohydrate precursors such as glucogenic amino acids (mainly alanine and glutamine), odd-chain fatty acids, glycerol, pyruvate, and lactate. Glycolysis, which occurs exclusively in the cytoplasm, is the sole source of ATP in cells that lack mitochondria (e.g., RBCs). In glycolysis, the breakdown of glucose molecules generates two net adenosine triphosphate ( ATP) molecules, which provide a readily available source of energy for various reactions in the cell, and two pyruvate molecules, which can be further converted into lactate (used in gluconeogenesis), acetyl-CoA (used in citric acid cycle), oxaloacetate (used in citric acid cycle), and alanine (used in transamination reactions). Glycolysis is the metabolic process by which glucose is broken down, while gluconeogenesis is the metabolic process by which glucose is synthesized.
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