As described before, many enzymes are involved in the glycolytic pathway by converting one intermediate to another. Control of these enzymes, such as hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase, can regulate glycolysis. The amount of oxygen available can also regulate glycolysis. The “Pasteur effect” describes how the availability of oxygen diminishes the effect of glycolysis, and decreased availability leads to an acceleration of glycolysis, at least initially. The mechanisms responsible for this effect include allosteric regulators of glycolysis (enzymes such as hexokinase). The “Pasteur effect” appears to mostly occur in tissue with high mitochondrial capacities, such as myocytes or hepatocytes. Still, this effect is not universal in oxidative tissue, such as pancreatic cells.[8]
It is critical to remember that there are a total of two 3-carbon sugars for every one glucose at the beginning of this phase. The enzyme glyceraldehyde-3-phosphate dehydrogenase metabolizes the G3P into 1,3-diphosphoglycerate by reducing NAD+ into NADH. Next, the 1,3-diphosphoglycerate loses a phosphate group through phosphoglycerate kinase to make 3-phosphoglycerate and creates an ATP through substrate-level phosphorylation. At this point, there are 2 ATP produced, one from each 3-carbon molecule. The 3-phosphoglycerate turns into 2-phosphoglycerate by phosphoglycerate mutase, and then enolase turns the 2-phosphoglycerate into phosphoenolpyruvate (PEP). In the final step, pyruvate kinase turns PEP into pyruvate and phosphorylates ADP into ATP through substrate-level phosphorylation, thus creating two more ATP. This step is also irreversible. Overall, the input for 1 glucose molecule is 2 ATP, and the output is 4 ATP and 2 NADH and 2 pyruvate molecules.[8]
Glycolysis precedes lactic acid fermentation; the pyruvate made in the former process serves as the prerequisite for the lactate made in the latter process. Lactic acid fermentation is the primary source of ATP in animal tissues with low metabolic requirements and little to no mitochondria. In erythrocytes, lactic acid fermentation is the sole source of ATP, as they lack mitochondria and mature red blood cells have little demand for ATP. Another part of the body that relies entirely or almost entirely on anaerobic glycolysis is the eyes lens, which is devoid of mitochondria, as their presence would lead to light scattering.[8]
The amount of glucose available for the process regulates glycolysis, which becomes available primarily in two ways: regulation of glucose reuptake or regulation of the breakdown of glycogen. Glucose transporters (GLUT) transport glucose from the outside of the cell to the inside. Cells containing GLUT can increase the number of GLUT in the cells plasma membrane from the intracellular matrix, therefore increasing the uptake of glucose and the supply of glucose available for glycolysis. There are five types of GLUTs. GLUT1 is present in RBCs, the blood-brain barrier, and the blood-placental barrier. GLUT2 is in the liver, beta-cells of the pancreas, kidney, and gastrointestinal (GI) tract. GLUT3 is present in neurons. GLUT4 is in adipocytes, heart, and skeletal muscle. GLUT5 specifically transports fructose into cells. Another form of regulation is the breakdown of glycogen. Cells can store extra glucose as glycogen when glucose levels are high in the cell plasma. Conversely, when levels are low, glycogen can be converted back into glucose. Two enzymes control the breakdown of glycogen: glycogen phosphorylase and glycogen synthase. The enzymes can be regulated through feedback loops of glucose or glucose 1-phosphate, or via allosteric regulation by metabolites, or from phosphorylation/dephosphorylation control.[8]
Fructose 2,6-bisphosphate is an allosteric regulator of PFK-1. High levels of fructose 2,6-bisphosphate increase the activity of PFK-1. Its production occurs through the action of phosphofructokinase-2 (PFK-2). PFK-2 has both kinase and phosphorylase activity and can transform fructose 6 phosphates to fructose 2,6-bisphosphate and vice versa. Insulin dephosphorylates PFK-2, activating its kinase activity, which increases fructose 2,6-bisphosphate and subsequently activates PFK-1. Glucagon can also phosphorylate PFK-2, which activates phosphatase, transforming fructose 2,6-bisphosphate back to fructose 6-phosphate. This reaction decreases fructose 2,6-bisphosphate levels and decreases PFK-1 activity.[8]
Glycolysis is the first step in cellular respiration, occurring in all living cells. Overall, the input for glycolysis is one glucose, two ATP and two NAD+ molecules giving rise to two pyruvate molecules, four ATP and two NADH.
FAQ
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