It phosphorylates many different sugars, including fructose and mannose. It has a higher affinity for glucose than does hexokinase.
It specifically phosphorylates glucose, rather than other sugars. Correct answer: It specifically phosphorylates glucose, rather than other sugars. Explanation : Glucokinase specifically phosphorylates the six-carbon sugar glucose. Example Question : Biochemistry. Which of the following is true of phosphofructokinase PFK? PFK acts to remove a phosphate group from fructosephosphate.
Explanation : Phosphofructokinase catalyzes the third step in glycolysis transforming fructose 6-phosphate to fructose-1,6-bisphosphate. Which of the following enzymes catalyzes an unfavorable step in glycolysis? Possible Answers: Enolase. Correct answer: Hexokinase. Explanation : Hexokinase catalyzes the first step of glycolysis, and this step requires the input of an ATP molecule. Possible Answers: Phosphofructokinase. Explanation : In the fourth step of glycolysis, the six-carbon molecule fructose-1,6-bisphosphate is cleaved into two separate three-carbon molecules: dihydroxyacetone phosphate and glyceraldehydephosphate.
Glycolysis will no longer be able to function to completion. Glycolysis will produce a net yield of four ATP molecules per molecule of glucose.
Only one pyruvate molecule will be formed per molecule of glucose. Correct answer: Only one pyruvate molecule will be formed per molecule of glucose.
Explanation : Triose phosphate isomerase is responsible for converting dihydroxyacetone phosphate into glyceraldehydephosphate. What is the role of phosphofructokinase-2 in glycolysis? Possible Answers: Phosphofructokinase-2 converts fructosephosphate to fructose-2,6-bisphosphate. Phosphofructokinase-2 converts fructose-2,6-bisphosphate to fructosephosphate.
Phosphofructokinase-2 converts fructose to fructosephosphate. Phosphofructokinase-2 converts fructosephosphate to fructose-1,6-bisphosphate. Phosphofructokinase-2 converts fructose to fructose-2,6-bisphosphate. Correct answer: Phosphofructokinase-2 converts fructosephosphate to fructose-2,6-bisphosphate. Explanation : Phosphofructokinase-2 converts fructosephosphate to fructose-2,6-bisphosphate. Copyright Notice. View Biochemistry Tutors.
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Company name. Copyright holder you represent if other than yourself. I am the owner, or an agent authorized to act on behalf of the owner of an exclusive right that is allegedly infringed. The reaction is therefore said to be enzyme-limited, and because its rate limits the rate of the whole reaction sequence, the step is called the rate-limiting step in the pathway.
In general, these rate-limiting steps are very exergonic reactions and are therefore essentially irreversible under cellular conditions. Afterwards they single out phosphofructokinase as the rate-limiting enzyme in glycolysis, a popular choice with other authors, such as Campbell p. Voet and Voet follow essentially the same pattern as above: The metabolic flux through an entire pathway is determined by its rate-determining step or steps which, by definition, is much slower than the following reaction step s.
PFK , an elaborately regulated enzyme functioning far from equilibrium, evidently is the major control point for glycolysis in muscle under most conditions. However, pyruvate kinase also has its partisans, as on p. Stryer hedges his bets: Phosphofructokinase is the key enzyme in the control of glycolysis p. Therefore, can we slow down the tumor growth when cutting the energy supply of tumor cells by leading them back to aerobic metabolism?
In normal cells, glucose is converted to pyruvate by the glycolysis pathway, with two ATPs consuming and four ATPs producing. So one glucose molecule produces 38 ATPs during complete oxidation. In tumor cells, the oxidation of pyruvate is replaced by producing lactate, catalyzed by lactate dehydrogenase LDH , with no ATP production. One glucose molecule produces only two ATPs in tumor cells.
Therefore, we usually use medium with high glucose to culture tumor cells, because they need more energy. Many signaling pathways are involved in this aerobic glycolysis process. Both the adenosine monophosphate-activated protein kinase AMPK and mammalian target of rapamycin mTOR pathways are either directly or indirectly involved in the glycolysis of tumor cells.
Famous oncoproteins c-Myc and hypoxia inducible factor 1 HIF-1 are involved in glycolysis by regulating key enzymes. It can also activate genes associated with mitochondrial biogenesis.
HIF-1 is a transcription factor that regulates gene expression in the event of decreased oxygen or hypoxia. The tumor suppressor p53 also shows an inhibitory effect on glycolysis.
Because it directly stimulates oxidative phosphorylation, loss of p53 shifts metabolism from oxidative phosphorylation to glycolysis. Increasingly, research has focused on these regulators, which provide potential therapeutic targets for cancer treatment.
Lung cancer is one of the most prevalent and deadly cancers in the world. Like many other kinds of solid tumors, lung cancer prefers aerobic glycolysis in the presence of oxygen for bioenergetic processes the Warburg effect. This is very important in clinical diagnosis, as a high aerobic glycolysis rate in lung cancer can be used clinically to monitor responses by the uptake of 2-deoxy 18 F fluoro-D-glucose 18 F-FDG , a radioactive modified HK substrate, with positron emission tomography PET.
With the exception of clinical diagnosis, the results from basic research have indicated that interrupting aerobic glycolysis with small molecules could inhibit many types of tumor cell survival. But whether the inhibition of glycolysis will be effective in the treatment of lung cancer is unclear. This regulator of glycolysis represented a novel pharmacodiagnostic marker.
Until now, no reports have suggested the regulation of lung cancer metastasis by altering aerobic glycolysis. This abnormal metabolic pathway should be targeted for lung cancer treatment.
More and more reports show that the key enzymes in the glycolysis pathway are upregulated in different kinds of tumors, which aggravates the abnormal metabolic pathway in tumor cells. Altenberg and Greulich showed key enzymes of glycolysis and their expression status in 24 cancers.
Eight out of 10 enzymes of glycolysis were found to be upregulated in lung cancer, which indicated that the key enzymes of the aerobic glycolysis pathway play important roles in lung cancer development. This first step of glycolysis is catalyzed by HK. The activity of HK is very important for the rate of glycolysis. This step not only activates glucose, but also restricts glucose in cells. HK is a rate-limiting enzyme of glucose oxidation reaction.
There are four important isoenzymes in mammalian organisms. Little is known about the regulatory characteristics of this isoform. Finally, mammalian HK IV is also referred to as glucokinase. There is a great deal of research on dissociative HK in lung cancer.
This second key step of glycolysis is catalyzed by PFK. It is an allosteric enzyme made of four subunits and controlled by several activators and inhibitors.
When serine 32 is phosphorylated, the negative charge causes the conformation of the enzyme to favor the FBPase2 activity. When not phosphorylated, PFK-2's activity is favored. PFK catalyzes the second key step of glycolysis, and is over-expressed in many kinds of cancers. Moreover, hypoxia highly induced PFK isozymes in lung carcinoma cells.
They also found that manipulation of miRa levels alters PFKM and lactate levels in the expected directions in vitro and in vivo. This last step of glycolysis is catalyzed by PK pyruvate kinase. This step is irreversible. PKL exists in the liver, kidneys, and erythrocytes. PKM1 exists in heart muscle, skeletal muscle, and the brain; PKM2 is mainly expressed in the brain and liver. PKM2 is also the main isoform in embryos and tumors.
Alternatively, PKR exists mainly in erythrocytes. Their outstanding work was published in Nature Letters. PK has been reported to be overexpressed in almost every kind of cancer, which shows its important function in glycolysis. For example, in normal lung proliferating cells, the tetrameric form of PKM2 is a highly active form used to produce pyruvate; however, in lung cancer cells, the dimeric form is always predominant.
Though the low active dimeric forms inhibited the glycolysis process, the phosphometabolites above pyruvate kinase, such as PEP, accumulated and were then available as precursors for synthetic processes, such as nucleic acid, amino acid, and phospholipid synthesis, which improved tumor malignancy.
They found that these activators influenced the growth of lung cancer cells in vitro and in vivo. Using short hairpin RNA to knockdown PKM2 and replacing it with PKM1, they found a reversal of the Warburg effect, judged by reduced lactate production and increased oxygen consumption. They also discovered that it correlated with a reduced ability to form tumors in nude mice xenografts. They demonstrated that PKM2 expression was necessary and important for aerobic glycolysis.
However, conceivably, as a very important key enzyme of glycolysis, PKM might play roles in all aspects of tumor development, and could be an efficient target for lung cancer therapy.
Its overexpression is observed in Rat1a fibroblasts, and in lymphoblastoid, Burkitt lymphoma, and lung cancer cells, which enhance the production of lactate and soft agar clonogenicity.
Tumor cells show different metabolism pathways to normal cells. They prefer anaerobic metabolism even under sufficient oxygen conditions, that is, the Warburg Effect. The three key enzymes are hexokinase, phosphofructokinase and pyruvate kinase. Together with lactate dehydrogenase, these four key enzymes improve tumor proliferation and migration, dependent or independent of glycolysis.
Although no evidence has been found on regulation of NSCLC metastasis by these key enzymes, lung cancer cell survival is indeed regulated by aerobic glycolysis and its key enzymes. The anaerobic metabolism of tumor cells provides new means and potential therapeutic targets for tumors, especially lung cancer.
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