Scientists at Scripps Research have made significant strides in their understanding of PLD3 and PLD4, two essential enzymes that break down nucleic acids such as DNA and RNA in cells. These enzymes aid in the prevention of nucleic acid accumulation. Nucleic acid accumulation can activate the immune system and result in autoimmune and immune disorders including lupus, Alzheimer’s disease and rheumatoid arthritis if left unchecked. Rheumatoid arthritis is a chronic inflammatory disease that can damage more than just one’s joints. This disease can affect a variety of body systems, including the skin, eyes, lungs, heart and blood vessels. PLD3 and PLD4 aid in the prevention of the diseases above by cleaning up the cellular environment and setting the threshold for what is considered an infection or not. Wow – I didn’t know these enzymes were so important to your health! Did you know about these enzymes?
The scientists were able to observe how the enzymes interact with their substrates during the degradation process by using X-ray crystallography to generate extremely precise, nearly atomic level models of these enzymes in different stages. X-ray crystallography first generates a photo that shows the pattern of diffracted x-rays, which scientists then use to develop a map of the enzyme’s molecular structure. Observing these models in various stages, the researchers found that both PLD3 and PLD4 use a two-step process to break down the nucleic acid. The enzyme first cleaves and links the DNA strand and separates a single nucleotide from the rest of the strand. Then, the enzyme releases this nucleotide.
Due to the fact that the enzymatic reaction described above occurs so quickly, the scientists used an alternative substrate to observe the enzyme’s structure during catalysis. The scientists incubated the enzymes together with a molecule that acted similarly to the substrate that the enzyme normally degrades (nucleic acid). However, the enzyme degrades this molecule much more slowly. After analyzing this slowed-down version of the enzymatic reaction between PLD3/PLD4 and nucleic acid, the scientists surprisingly discovered the function of phosphatase activity in both of the enzymes. How interesting!
The study also examined PLD3 and PLD4 mutations associated with diseases, specifically those connected to spinocerebellar ataxia and Alzheimer’s disease. While certain mutations led to reduced enzyme activity, making it more difficult to eliminate nucleic acids, others, including those associated with late-onset Alzheimer’s, enhanced enzyme activity. What a surprise! However, this increased enzyme activity seemed to lead to the instability and aggregation of the enzyme which are frequently linked to neurodegenerative diseases. After reaching these findings, the researchers are beginning to think about potential treatment plans. Some possible treatments include inhibiting the enzymes in cases where they are overactive. Other treatment ideas include replacing the enzymes in individuals who have non-functional versions of the enzymes. Can you think of any other possible treatment ideas that could work?
This article connects to AP Biology because it demonstrates the significance of enzymes. Enzymes are significant because they are vital to nearly every biological process due to the fact that they speed up chemical reactions that are necessary for life. More specifically, they are proteins that catalyze reactions, helping to break down molecules, build new ones, and maintain cellular processes.
However, as discussed in AP Biology, enzymes are susceptible to environmental influences such as temperature, pH, and substrate concentration. If these environmental factors are not within a specific range, the enzymes may not function to their fullest potential. For example, as temperature increases, enzyme function will increase until the enzyme ultimately denatures at a temperature that is too hot. When the temperature becomes too hot, the shape of the enzyme will change because the quaternary, tertiary, and secondary protein structures of the enzymes will be destroyed, leaving simply the primary structure (covalent bonds). Similarly with pH, specific enzymes have their own optimal pHs in which they can function best. If the pH deviates from this optimal pH, the increase of OH-/H+ will disrupt the quaternary, tertiary, and secondary protein levels of the enzyme and cause the protein to denature. In both of these cases, the quaternary, tertiary, and secondary protein levels were destroyed because their bonds such as hydrogen bonds, van der Waals interactions, disulfide bonds, ionic bonds, hydrophobic interactions are not strong enough to withstand extreme conditions. Lastly, substrate concentration can also affect the function of the enzymes. As the amount of substrate increases, the enzyme function increases until the enzyme function plateaus because the enzyme can only bind to so many substrates.
In the context of the study, when PLD3 and PLD4 activity is disrupted either by environmental factors or genetic mutations that alter their structure, nucleic acid accumulates which may lead to conditions like autoimmune diseases or neurodegenerative disorders. The study highlighted how mutations in these enzymes could reduce their activity or make them overactive, both of which could have harmful effects. Overall, the findings in the study emphasize the significance of understanding how enzyme function is influenced by environmental factors and other influences, as imbalances can contribute to dangerous responses such as disease.
Personally, this article made me even more grateful for my health. I realized that even little changes in my body could potentially cause major health issues. I am also grateful for the individuals who are researching about human health and improving society each day!
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