Information

Why some cells don't produce purines?

Why some cells don't produce purines?



We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

It is said that erythrocytes, polymorphonuclear leukocytes and brain cannot produce purines. And the reason given as per this site is:

Human brain tissue has a low level of PRPP glutamyl amidotransferase (reaction Image, Figure 33-2) and hence depends in part on exogenous purines. Erythrocytes and polymorphonuclear leukocytes cannot synthesize 5-phosphoribosylamine (structure III, Figure 33-2) and therefore utilize exogenous purines to form nucleotides.

My question is why do these cells don't produce the required enzymes for the synthesis of purines? What could be the functional significance for such absence?

My attempt : At first I thought that Erythrocytes as such don't have nucleus so they don't need purine synthesis for cell division , but I don't understand why then they need purines from external source( as said in the above site). Also brain cells are neurons and neuroglia, of which former doesn't divide( except in some areas of brain) but they too need purines. The later divide but they don't produce required enzyme. Why?

So my questions are:

  1. Why do cells which don't replicate need purines?( May be for formation of Coenzymes , correct me if Iam wrong)

  2. Why do the cells which divide too don't produce required proteins(enzymes)?


I am going to throw this idea out there. I was unable to find it stated anywhere so far.

There are several very ancient parasites that make their homes inside erythrocytes and neutrophils. Plasmodium is one, the causative agent of malaria. Trypanosoma is another. These things are ancient degenerate eukaryotes and their lifestyle as intracellular parasites is probably ancient too.

These things cannot make purines either but they need them and they need a lot of them, because they are reproducing fast. If the host cell does not have the machinery to make purines, that machinery cannot be hijacked by the parasite to really crank out the purines. The best they can do is hijack the salvage pathways these cells have.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC259377/

The apparent competition between parasites and host cells for available purines suggests that depletion of extracellular purines should be considered as an approach to treating extracellular trypanosome infections.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405406/

Plasmodium species parasites, like many other protozoan parasites, are purine auxotrophs, unable to perform de novo purine biosynthesis. They rely on the host to provide purines

That does not explain brain cells - unless lack of purine synthesis is a defense of brain cells against Toxoplasma, yet another eukaryotic parasite.

Nothing would please me more than for someone to poke holes in this theory. A prediction from this theory: erythryocytes in all animals should lack purine synthesis - including birds, who suffer from a form of malaria and whose erythrocytes do have nuclei.


Bookshelf

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science 2002.

  • By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.


Molecular Biology of the Cell. 4th edition.

Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends in part on the adaptive immune system (discussed in Chapter 24), which remembers previous encounters with specific pathogens and destroys them when they attack again. Adaptive immune responses, however, are slow to develop on first exposure to a new pathogen, as specific clones of B and T cells have to become activated and expand it can therefore take a week or so before the responses are effective. By contrast, a single bacterium with a doubling time of one hour can produce almost 20 million progeny, a full-blown infection, in a single day. Therefore, during the first critical hours and days of exposure to a new pathogen, we rely on our innate immune system to protect us from infection.

Innate immune responses are not specific to a particular pathogen in the way that the adaptive immune responses are. They depend on a group of proteins and phagocytic cells that recognize conserved features of pathogens and become quickly activated to help destroy invaders. Whereas the adaptive immune system arose in evolution less than 500 million years ago and is confined to vertebrates, innate immune responses have been found among both vertebrates and invertebrates, as well as in plants, and the basic mechanisms that regulate them are conserved. As discussed in Chapter 24, the innate immune responses in vertebrates are also required to activate adaptive immune responses.


Fermentation

Fermentation starts with glycolysis, but it does not involve the latter two stages of aerobic cellular respiration (the Krebs cycle and oxidative phosphorylation). During glycolysis, two NAD+ electron carriers are reduced to two NADH molecules and 2 net ATPs are produced. The NADH must be oxidized back so that glycolysis can continue and cells can continue making 2 ATPs. The cells cannot make more than 2 ATP in fermentation because oxidative phosphorylation does not happen due to a lack of oxygen. There are two types of fermentation, alcoholic fermentation and lactic acid fermentation. Our cells can only perform lactic acid fermentation however, we make use of both types of fermentation using other organisms.

Alcoholic Fermentation

Alcoholic fermentation The process by which this happens is summarized in Figure (PageIndex<2>). The two pyruvate molecules are shown in this diagram come from the splitting of glucose through glycolysis. This process also produces 2 molecules of ATP. Continued breakdown of pyruvate produces acetaldehyde, carbon dioxide, and eventually ethanol. Alcoholic fermentation requires the electrons from NADH and results in the generation of NAD+.

Yeast in bread dough also uses alcoholic fermentation for energy and produces carbon dioxide gas as a waste product. The carbon dioxide that is released causes bubbles in the dough and explains why the dough rises. Do you see the small holes in the bread in Figure (PageIndex<3>)? The holes were formed by bubbles of carbon dioxide gas.

Figure (PageIndex<3>): Holes from carbon dioxide gas in bread dough are left behind after the bread bakes.

Lactic Acid Fermentation

Lactic acid fermentation is carried out by certain bacteria, including the bacteria in yogurt. It is also carried out by your muscle cells when you work them hard and fast. This is how the muscles of the sprinter in Figure (PageIndex<1>)get energy for their short-duration but intense activity. The process by which this happens is summarized in Figure (PageIndex<2>). Again, two pyruvate and two ATP molecules result from glycolysis. Reduction of pyruvate using the electrons carried by NADH produces lactate (i.e. lactic acid). While this is similar to alcoholic fermentation, there is no carbon dioxide produced in this process.

Did you ever run a race, lift heavy weights, or participate in some other intense activity and notice that your muscles start to feel a burning sensation? This may occur when your muscle cells use lactic acid fermentation to provide ATP for energy. The buildup of lactic acid in the muscles causes the feeling of burning. The painful sensation is useful if it gets you to stop overworking your muscles and allow them a recovery period during which cells can eliminate the lactic acid.


What is a Mutation?

Over a lifetime, our DNA can undergo changes or mutations in the sequence of bases: A, C, G and T. This results in changes in the proteins that are made. This can be a bad or a good thing.

A mutation is a change that occurs in our DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental factors such as UV light and cigarette smoke. Mutations can occur during DNA replication if errors are made and not corrected in time. Mutations can also occur as the result of exposure to environmental factors such as smoking, sunlight and radiation. Often cells can recognize any potentially mutation-causing damage and repair it before it becomes a fixed mutation.

Mutations contribute to genetic variation within species. Mutations can also be inherited, particularly if they occur in a germ cell (reproductive egg or sperm). Mutations that have a positive effect are more likely to be continually passed on. For example, the disorder sickle cell anaemia is caused by a mutation in the gene that instructs the building of a protein called hemoglobin. This causes the red blood cells to become an abnormal, rigid, sickle shape. However, in African populations, having this mutation also protects against malaria.

However, mutation can also disrupt normal gene activity and cause diseases, like cancer. Cancer is the most common human genetic disease it is caused by mutations occurring in a number of growth-controlling genes. Sometimes faulty, cancer-causing genes can exist from birth, increasing a person’s chance of getting cancer.

Figure 1. An illustration to show an example of a DNA mutation. Image credit: Genome Research Limited


Henrietta Lacks’ ‘Immortal’ Cells

Medical researchers use laboratory-grown human cells to learn the intricacies of how cells work and test theories about the causes and treatment of diseases. The cell lines they need are “immortal”—they can grow indefinitely, be frozen for decades, divided into different batches and shared among scientists. In 1951, a scientist at Johns Hopkins Hospital in Baltimore, Maryland, created the first immortal human cell line with a tissue sample taken from a young black woman with cervical cancer. Those cells, called HeLa cells, quickly became invaluable to medical research—though their donor remained a mystery for decades. In her new book, The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells, Henrietta Lacks, and documents the cell line's impact on both modern medicine and the Lacks family.

Related Content

Who was Henrietta Lacks?
She was a black tobacco farmer from southern Virginia who got cervical cancer when she was 30. A doctor at Johns Hopkins took a piece of her tumor without telling her and sent it down the hall to scientists there who had been trying to grow tissues in culture for decades without success. No one knows why, but her cells never died.

Why are her cells so important?
Henrietta’s cells were the first immortal human cells ever grown in culture. They were essential to developing the polio vaccine. They went up in the first space missions to see what would happen to cells in zero gravity. Many scientific landmarks since then have used her cells, including cloning, gene mapping and in vitro fertilization.

There has been a lot of confusion over the years about the source of HeLa cells. Why?
When the cells were taken, they were given the code name HeLa, for the first two letters in Henrietta and Lacks. Today, anonymizing samples is a very important part of doing research on cells. But that wasn’t something doctors worried about much in the 1950s, so they weren’t terribly careful about her identity. When some members of the press got close to finding Henrietta’s family, the researcher who’d grown the cells made up a pseudonym—Helen Lane—to throw the media off track. Other pseudonyms, like Helen Larsen, eventually showed up, too. Her real name didn’t really leak out into the world until the 1970s.

How did you first get interested in this story?
I first learned about Henrietta in 1988. I was 16 and a student in a community college biology class. Everybody learns about these cells in basic biology, but what was unique about my situation was that my teacher actually knew Henrietta’s real name and that she was black. But that’s all he knew. The moment I heard about her, I became obsessed: Did she have any kids? What do they think about part of their mother being alive all these years after she died? Years later, when I started being interested in writing, one of the first stories I imagined myself writing was hers. But it wasn’t until I went to grad school that I thought about trying to track down her family.

A HeLa cancer cell dividing. (© Dr. Thomas Deerinck / Visuals Unlimited / Corbis) The metaphase stage of a human HeLa cell division. (© Dr. Richard Kessel / Dr. Gene Shih / Visuals Unlimited / Corbis) Subspecies of HeLa cells have evolved in labs and some feel that the cell line is no longer human, but a new microbial life form. These cells are shown in green the cytoplasm is red and structures within the cytoplasm are blue. (© Nancy Kedersha / Science Faction / Corbis) The prophase stage of mitosis in the division of these human HeLa cells. (© Dr. Richard Kessel / Dr. Gene Shih / Visuals Unlimited / Corbis) This fluorescence micrograph of a HeLa cell shows the cytoskeletal microfilaments in red and nuclei stain with Hoechst in blue. (© Visuals Unlimited / Corbis)

How did you win the trust of Henrietta’s family?
Part of it was that I just wouldn’t go away and was determined to tell the story. It took almost a year even to convince Henrietta’s daughter, Deborah, to talk to me. I knew she was desperate to learn about her mother. So when I started doing my own research, I’d tell her everything I found. I went down to Clover, Virginia, where Henrietta was raised, and tracked down her cousins, then called Deborah and left these stories about Henrietta on her voice mail. Because part of what I was trying to convey to her was I wasn’t hiding anything, that we could learn about her mother together. After a year, finally she said, fine, let’s do this thing.

When did her family find out about Henrietta’s cells?
Twenty-five years after Henrietta died, a scientist discovered that many cell cultures thought to be from other tissue types, including breast and prostate cells, were in fact HeLa cells. It turned out that HeLa cells could float on dust particles in the air and travel on unwashed hands and contaminate other cultures. It became an enormous controversy. In the midst of that, one group of scientists tracked down Henrietta’s relatives to take some samples with hopes that they could use the family’s DNA to make a map of Henrietta’s genes so they could tell which cell cultures were HeLa and which weren’t, to begin straightening out the contamination problem.

So a postdoc called Henrietta’s husband one day. But he had a third-grade education and didn’t even know what a cell was. The way he understood the phone call was: “We’ve got your wife. She’s alive in a laboratory. We’ve been doing research on her for the last 25 years. And now we have to test your kids to see if they have cancer.” Which wasn’t what the researcher said at all. The scientists didn’t know that the family didn’t understand. From that point on, though, the family got sucked into this world of research they didn’t understand, and the cells, in a sense, took over their lives.

How did they do that?
This was most true for Henrietta’s daughter. Deborah never knew her mother she was an infant when Henrietta died. She had always wanted to know who her mother was but no one ever talked about Henrietta. So when Deborah found out that this part of her mother was still alive she became desperate to understand what that meant: Did it hurt her mother when scientists injected her cells with viruses and toxins? Had scientists cloned her mother? And could those cells help scientists tell her about her mother, like what her favorite color was and if she liked to dance.

Deborah’s brothers, though, didn’t think much about the cells until they found out there was money involved. HeLa cells were the first human biological materials ever bought and sold, which helped launch a multi-billion-dollar industry. When Deborah’s brothers found out that people were selling vials of their mother’s cells, and that the family didn’t get any of the resulting money, they got very angry. Henrietta’s family has lived in poverty most of their lives, and many of them can’t afford health insurance. One of her sons was homeless and living on the streets of Baltimore. So the family launched a campaign to get some of what they felt they were owed financially. It consumed their lives in that way.

These HeLa cells were stained with special dyes that highlight specific parts of each cell. The DNA in the nucleus is yellow, the actin filaments are light blue and the mitochondria—the cell's power generators—are pink. (© Omar Quintero) Henrietta Lacks' cells were essential in developing the polio vaccine and were used in scientific landmarks such as cloning, gene mapping and in vitro fertilization. (Courtesy of the Lacks family) Margaret Gey and Minnie, a lab technician, in the Gey lab at Johns Hopkins, circa 1951. (Courtesy of Mary Kubicek) In The Immortal Life of Henrietta Lacks, journalist Rebecca Skloot tracks down the story of the source of the amazing HeLa cells. (Courtesy of Random House, Inc.) Skloot first learned about Henrietta in 1988 from a community college biology teacher. (Courtesy of Random House, Inc.)

What are the lessons from this book?
For scientists, one of the lessons is that there are human beings behind every biological sample used in the laboratory. So much of science today revolves around using human biological tissue of some kind. For scientists, cells are often just like tubes or fruit flies—they’re just inanimate tools that are always there in the lab. The people behind those samples often have their own thoughts and feelings about what should happen to their tissues, but they’re usually left out of the equation.

And for the rest of us?
The story of HeLa cells and what happened with Henrietta has often been held up as an example of a racist white scientist doing something malicious to a black woman. But that’s not accurate. The real story is much more subtle and complicated. What is very true about science is that there are human beings behind it and sometimes even with the best of intentions things go wrong.

One of the things I don’t want people to take from the story is the idea that tissue culture is bad. So much of medicine today depends on tissue culture. HIV tests, many basic drugs, all of our vaccines—we would have none of that if it wasn’t for scientists collecting cells from people and growing them. And the need for these cells is going to get greater, not less. Instead of saying we don’t want that to happen, we just need to look at how it can happen in a way that everyone is OK with.


Cell biology: The new cell anatomy

A menagerie of intriguing cell structures, some long-neglected and others newly discovered, is keeping biologists glued to their microscopes.

In 2008, Chalongrat Noree faced an unenviable task: manually surveying hundreds of yeast strains under a microscope. Each strain had a different protein tagged with a fluorescent label, and Noree, a graduate student at the University of California, San Diego, was looking for interesting structures in the cells.

But it wasn't long until Noree's labour yielded results: within a month, he began finding a wide variety of proteins assembling into clusters or long strands. “Imagine every week you found a new intracellular structure,” says Jim Wilhelm, a cell biologist and Noree's adviser. “If it were a slot machine, it would be paying off every other time you pulled the handle.”

These days, textbook diagrams of cell structures such as the nucleus, mitochondrion, ribosome and Golgi apparatus are beginning to seem out of date. New imaging techniques, genome data, interest from disciplines outside cell biology and a bit of serendipity are drawing attention to an intricate landscape of tubes, sacs, clumps, strands and capsules that may be involved in everything from intercellular communication to metabolic efficiency. Some could even be harnessed for use in drug delivery or in synthesis of industrial products, such as biofuels.

Some of these structures have been known for decades, whereas others have only recently come to light. Wilhelm's team, for instance, has found six kinds of filament that either had never been described, or had been largely passed over. “You figure, how many structures could have been missed in the cell?” says Wilhelm. “Apparently, a lot more than you would imagine.”

Lines of communication

One structure that is receiving fresh scrutiny is the membrane nanotube: a thin thread of membrane suspended between cells. In 2000, Amin Rustom, then a graduate student at Heidelberg University in Germany, was using a newly acquired dye to look at rat tumour cells under a fluorescence microscope. But he decided to skip some washing steps in the protocol. “He said, 'I saw something — I don't know what it is, but it looks interesting',” recalls his former adviser, Hans-Hermann Gerdes, a cell biologist now at the University of Bergen in Norway. The tubes that Rustom had noticed were so straight that Gerdes initially wondered if they were scratches on the dish.

The team concluded in a 2004 study 1 that the structures, which could span the distance of several cells, were channels that could transport small cellular organelles. That same year, Daniel Davis, a molecular immunologist at Imperial College London, and his colleagues proposed that immune cells might send signals to each other along such tubes 2 . At the time, Davis recalls, “There would always be people in the audience who would say, 'I saw those strands in the late 1970s or 80s'.” But earlier observers paid little heed to the tubes.

The 2004 reports prompted more studies, which have found nanotubes in many types of mammalian cell. Davis's team found that nanotubes could help certain white blood cells to kill cancer cells, either by acting as a tether that draws the cancer cell close or by providing a conduit for delivering lethal signals 3 . Nanotubes can also conduct electrical signals, which might enable cells to coordinate during migration or wound healing, according to a 2010 study by Gerdes and his colleagues 4 . HIV and prions — infectious, misfolded proteins — may even travel along the tubes 5,6 .

Some researchers are sceptical that nanotubes can form open channels. “It's not clear that there's a real continuous tunnel,” says Jennifer Lippincott-Schwartz, a cell biologist at the US National Institutes of Health in Bethesda, Maryland. And so far, nanotubes have been studied mainly in cell culture. Blocking nanotube formation in living organisms might give clues to their importance, says Davis. But such manipulations often disturb other crucial processes.

Productivity hotspots

Researchers have long puzzled over how some metabolic processes work so efficiently. If the proteins involved are not close together, intermediate molecules could get lost in the “bewildering mass of enzymes in the cell”, says Stephen Benkovic, a chemical biologist at Pennsylvania State University in University Park. Proteins often assemble to carry out a particular task — a large complex is required to copy DNA, for example — but Benkovic and others have wondered whether metabolic enzymes might cluster together in a multistep assembly line, passing sometimes-unstable molecules from one 'worker' to the next.

Benkovic's group found evidence that this clustering does occur in enzymes that produce a precursor of purine nucleotides, which are components of DNA and RNA. The team tagged each enzyme with a fluorescent label and observed them in living cells under the microscope. When a cell was deprived of purines, the enzymes grouped together in a cluster, which the team called the 'purinosome' 7 . Last year, the team reported that purinosomes are nestled in a mesh of protein fibres called microtubules, like berries in a bramble bush 8 . The molecules produced by purinosomes can be converted to the cellular fuel adenosine triphosphate, so Benkovic speculates that purinosomes may help power the transport of organelles and materials around the cell on microtubule tracks.

Edward Marcotte, a systems biologist at the University of Texas at Austin, advises caution in interpreting these results, however. He and his colleagues have seen enzyme clusters as well: in 2009, they reported that they had found 180 types of protein forming clumps in starved yeast cells 9 . But it is not clear whether the clumps serve a useful purpose — such as improving metabolic efficiency or acting as storage depots — or are a result of cellular failures brought on by starvation, says Marcotte.

Some researchers are taking a closer look at elegant bacterial protein containers called microcompartments. First seen about 50 years ago, these polyhedron-shaped protein capsules resemble the outer shell of a virus 10 . But unlike viruses, which package genetic material, microcompartments contain enzymes that carry out important reactions, such as converting carbon dioxide into a form of carbon that is usable by the cell. Scientists suspect that the shells make reactions more efficient, keep toxic intermediate products away from the rest of the cell and protect enzymes from molecules that could hinder their performance.

In 2005, protein crystallographers helped to reveal the capsules' finer details. Microcompartments “simply hadn't attracted the attention yet of structural biologists”, says Todd Yeates, a structural biologist himself at the University of California, Los Angeles. He and his colleagues found that some shell proteins assemble into six-sided tiles that come together to form the sides of a microcompartment 11 . Each tile has a hole in the centre that could allow molecules to pass through.

In addition to having an orderly structure, microcompartments can also line up in neat rows. Pamela Silver, a synthetic biologist at Harvard Medical School in Boston, Massachusetts, and her colleagues reported 12 last year that in cyanobacteria, certain microcompartments called carboxysomes “more or less stayed in a line down the centre of the cell”, says Silver. This tidy arrangement allows cells to allot carboxysomes evenly to daughter cells when dividing.

Biologists are now eager to exploit these capsules for industrial uses by loading them with different enzymes. For instance, Yeates and his team are planning to try engineering microcompartments to produce biofuel. Some researchers have managed to package fluorescent proteins or enzymes from other species into the shells, suggesting that it is possible to modify the capsules' contents.

Microcompartments still offer plenty of unexplored territory. Scientists aren't sure, for instance, exactly how enzymes are organized inside the capsules, says Cheryl Kerfeld, a structural biologist at Lawrence Berkeley National Laboratory in Berkeley, California. “We don't really know what it looks like in there.”

Other subcellular packages drawing attention are exosomes — tiny membrane-enclosed sacs that form inside the cell and are later spat out. These nanoscale vessels were discovered in the 1980s and then ignored for about a decade — considered a way of bagging up cellular rubbish. “People thought they were junk, basically,” says Jan Lötvall, a clinical allergist at the University of Gothenburg in Sweden.

Interest in exosomes picked up in 1996, when Graça Raposo, a cell biologist now at the Curie Institute and the National Centre for Scientific Research in Paris, and her colleagues scrutinized exosomes spat out by B cells, a type of white blood cell. Although the technology to examine them — electron microscopy — wasn't new, it wasn't very popular at the time because “it was just old-fashioned”, says Raposo. Using it and other techniques, the team reported that the humble vessels might do something useful: display scraps of pathogen protein on their surfaces, spurring immune cells to mount defences against an infection 13 . Scientists became even more intrigued when Lötvall's team reported in 2007 that exosomes could carry messenger RNA 14 , some of which could be picked up and translated in a recipient cell. This suggested that the shipments might allow cells to affect protein production in their neighbours. The study “really showed that exosomes were a vehicle of communicating important information between cells”, says Clotilde Théry, a cell biologist who is also at the Curie Institute.

Researchers are now trying to use exosomes to deliver drugs to specific parts of the body — with the hope that, because exosomes are 'natural', they might be less likely to be toxic or provoke an immune response than other vessels, such as artificial lipid sacs or protein shells. This year, Matthew Wood, a neuroscientist at the University of Oxford, UK, and his colleagues reported 15 an attempt in mice: the team loaded exosomes with artificial RNA intended to hinder production of a protein involved in Alzheimer's disease and tagged them with a molecule directing them to neurons and the blood–brain barrier. The exosomes successfully delivered their cargo and reduced production of the protein with no obvious ill effects, the team found. Other scientists are trying to fish exosomes out of body fluids and analyse their contents to diagnose cancer or deploy exosomes to provoke immune responses against tumours.

Finally, Wilhelm's group and others have found filaments that string together enzymes by the hundreds or thousands — enough, in some cases, to span nearly the entire cell. One of the filament-forming enzymes Wilhelm's team found was CTP synthase, which makes a building block for DNA and RNA 16 . Two other teams discovered the same filaments in fruitflies and bacteria at around the same time 17,18 . One researcher, Ji-Long Liu, a cell biologist at the Medical Research Council Functional Genomics Unit at the University of Oxford, named them cytoophidia (or 'cell serpents') because of their snake-like shapes in fly cells. Wilhelm suspects that researchers found the same filaments in the 1980s but never identified the protein.

These structures could allow the cell to turn enzymes on and off en masse, suggests Wilhelm. For instance, if the enzymes in a filament are inactive, the cell could activate all of them by dissolving the strand.

In some bacteria, enzyme filaments also seem to serve a structural purpose, somewhat like the actin filaments that are part of the cytoskeleton in more complex cells. When Zemer Gitai, a cell biologist at Princeton University in New Jersey, and his colleagues studied the structures in a comma-shaped bacterium called Caulobacter crescentus, they found that CTP-synthase filaments kept the cells' curvature in check. If there was too little of the enzyme, the cells curled up tightly if there was too much, they straightened out 18 .

It is not clear why curvature is important for the bacterium, says Gitai, but the findings suggest that the cells may have co-opted enzyme filaments to preserve cell shape. Researchers already suspect that actin is related to the enzyme hexokinase. It is possible that the cytoskeleton arose from filaments that originally formed to regulate the cell's metabolism, Gitai says.

Although the purpose and importance of some of these emerging structures is not yet clear, the research illustrates that the act of simply observing cells and their contents is alive and well. “A key aspect of doing great science is exploration,” says Davis. “I think that there's a tremendous amount that we learn just by watching.”


ATP vs. GTP/CTP - Why does nature use ATP for energy coupling? (Apr/03/2006 )

I am preparing my final exam and just asked myself a simple question which turned out to be not so simple.

Why does nature use (in most cases) ATP to couple energy into reactions? Why not GTP or CTP?
(Actually, GTP is used for some processes, but I don't know any reactions that use CTP)
The amount of energy they provide upon hydrolysis into ADP/GDP/CDP and Pyrophosphate is the same.
So there should be some evolutionary advantage, which is the reason to favor ATP.

hi
i don't have a strick answer, but i realized once that GTP gives some energy in reactions and also serves as cofactor for G proteins.
And A and G are purines. So probably purines are better holded than pyrimidines.
But why A vs G .

Hi,
ATP: Adenosine is the all-purpose nucleotide, assuming several roles in almost every pathway in the cell. Adenosine can be used as a source of energy, acting alone as ATP or combined with other nucleotides, like niacin in NAD or riboflavin in FAD. Enzymes which directly hydrolyse ATP into ADP and phosphate are called ATPases. ATPases are found throughout the cell performing a wide variety of functions from pumping ions across the membrane to running all of the cytoplasmic motors that shuttle material around the cell and drive cilia, flagella, and muscles. Adenosine is also used extensively by the cell as a source of phosphates for modifying proteins - several proteins require phosphorylation to be activated or inactivated, and this is used by the cell to control which enzymes are on or off. The enzymes which phosphorylate other proteins are called kinases and all require ATP to function. There are several other functions of Adenosine that I won't go into here to save space.

GTP
: Guanosine is used similarly to Adenosine, but in fewer roles. There are a very few instances in which GTP is used as a phosphate donor or an energy source, most notable of which is Tubulin, which must hydrolyze GTP to GDP to form the microtubules of the cytoskeleton. There are several other GTPase enzymes in the cell, however most of these enzymes are not used for their enzymatic properties, but rather are used to transmit signals throughout the cell. G-proteins are a specific class of GTPases which use their binding to GTP to interact with other enzymes to activate the cell. Many hormones and neurotransmitters have receptors that use G-proteins to transmit their signals to the rest of the cell. There are several other GTPases, including the Ras and Rab families of small GTPases, that are all also used to transmit signals and to control other intercellular traffic through their binding to GTP.

UTP
: Uridine is used for a different purpose from the purine nucleotides. The most common example of this is in glycogen synthesis. Many cells in the body (especially in the liver) store glucose (sugar) in the form of glycogen, a complex starch composed of long, branching chains of glucose molecules. To enhance this reaction, free glucose molecules prepared for addition by reacting them with UTP to produce UDP-glucose and free phosphate. This makes the glucose molecules more reactive, since the glucose-phosphate bond in UDP-glucose is a high energy bond. As the UDP-glucose is added to glycogen, the UDP is released, and the energy is used to attach the glucose to the glycogen molecule. In fact, Uridine is used for UDP-glucose, UDP-galactose, UDP-mannose, etc., the building blocks of numerous carbohydrates that are essential for many cellular functions.

CTP
: Cytidine is used very similarly to Uridine, however instead of sugars, CTP is used with fats. CDP-diacylglycerol, CDP-ethanolamine, and CDP-choline are the building blocks of the phospholipids that make up the cell membrane. Since all cells require intact membranes to survive, this is an exceedingly important cellular function.

The purine nucleotides have a wide range of uses, while the pyrimidines act more as handles than anything else. This is probably due to the more reactive nature of the purine rings, which makes ATP especially an ideal co-enzyme.

I doubt there's an energy reason -- as you noted, there's an equal amount of energy in the phospate bonds of other nucleotides.

It's likely that this is an evolutionary preference -- an early enzyme worked with ATP, and through evolution, other orthologous genes arose through gene duplication and genetic drift. Nature doesn't waste time reinventing the wheel, so since the early ancestor used ATP, so do the bulk of its orthologs.

As the cell became more complex, the ability to separate energy-producing enzymatic reactions on the basis of the nucleotide providing the bonds becomes beneficial, and thus orthologs which preferencially use GTP, for example, were selected for.

The inter-related nature of these genes can not only be seen at the sequence level, but also in their catalytic abilities -- most of these enzymes show a strong preference for "their" NTP, but will also catalyse other nucleotide triphosphates as well, at a greatly reduced rate.

A similar example can be found regarding the isocitrate dehydrogenases -- some of which reduce NAD (to make ATP, BTW) and others of which reduce NADP (in the synthesis of certain amino acids).

BTW, I suppose it is equally likely that ATP is the most wide-spread energy-providing NTP used by the cell because it was the first one that could be synthesized by the cell, or that it is the one most easily synthesized, or some other reasons (likely a combination of reasons).


Karyokinesis, also known as mitosis, is divided into a series of phases—prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus (Figure 2). Karyokinesis is also called mitosis.

Art Connection

Figure 2. Karyokinesis (or mitosis) is divided into five stages—prophase, prometaphase, metaphase, anaphase, and telophase. The pictures at the bottom were taken by fluorescence microscopy (hence, the black background) of cells artificially stained by fluorescent dyes: blue fluorescence indicates DNA (chromosomes) and green fluorescence indicates microtubules (spindle apparatus). (credit “mitosis drawings”: modification of work by Mariana Ruiz Villareal credit “micrographs”: modification of work by Roy van Heesbeen credit “cytokinesis micrograph”: Wadsworth Center/New York State Department of Health scale-bar data from Matt Russell)

Which of the following is the correct order of events in mitosis?

  1. Sister chromatids line up at the metaphase plate. The kinetochore becomes attached to the mitotic spindle. The nucleus reforms and the cell divides. Cohesin proteins break down and the sister chromatids separate.
  2. The kinetochore becomes attached to the mitotic spindle. Cohesin proteins break down and the sister chromatids separate. Sister chromatids line up at the metaphase plate. The nucleus reforms and the cell divides.
  3. The kinetochore becomes attached to the cohesin proteins. Sister chromatids line up at the metaphase plate. The kinetochore breaks down and the sister chromatids separate. The nucleus reforms and the cell divides.
  4. The kinetochore becomes attached to the mitotic spindle. Sister chromatids line up at the metaphase plate. Cohesin proteins break down and the sister chromatids separate. The nucleus reforms and the cell divides.

During prophase, the “first phase,” the nuclear envelope starts to dissociate into small vesicles, and the membranous organelles (such as the Golgi complex or Golgi apparatus, and endoplasmic reticulum), fragment and disperse toward the periphery of the cell. The nucleolus disappears (disperses). The centrosomes begin to move to opposite poles of the cell. Microtubules that will form the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly with the aid of condensin proteins and become visible under a light microscope.

Figure 3. During prometaphase, mitotic spindle microtubules from opposite poles attach to each sister chromatid at the kinetochore. In anaphase, the connection between the sister chromatids breaks down, and the microtubules pull the chromosomes toward opposite poles.

During prometaphase, the “first change phase,” many processes that were begun in prophase continue to advance. The remnants of the nuclear envelope fragment. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and discrete. Each sister chromatid develops a protein structure called a kinetochore in the centromeric region (Figure 3). The proteins of the kinetochore attract and bind mitotic spindle microtubules. As the spindle microtubules extend from the centrosomes, some of these microtubules come into contact with and firmly bind to the kinetochores. Once a mitotic fiber attaches to a chromosome, the chromosome will be oriented until the kinetochores of sister chromatids face the opposite poles. Eventually, all the sister chromatids will be attached via their kinetochores to microtubules from opposing poles. Spindle microtubules that do not engage the chromosomes are called polar microtubules. These microtubules overlap each other midway between the two poles and contribute to cell elongation. Astral microtubules are located near the poles, aid in spindle orientation, and are required for the regulation of mitosis.

During metaphase, the “change phase,” all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other by cohesin proteins. At this time, the chromosomes are maximally condensed.

During anaphase, the “upward phase,” the cohesin proteins degrade, and the sister chromatids separate at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule is attached. The cell becomes visibly elongated (oval shaped) as the polar microtubules slide against each other at the metaphase plate where they overlap.

During telophase, the “distance phase,” the chromosomes reach the opposite poles and begin to decondense (unravel), relaxing into a chromatin configuration. The mitotic spindles are depolymerized into tubulin monomers that will be used to assemble cytoskeletal components for each daughter cell. Nuclear envelopes form around the chromosomes, and nucleosomes appear within the nuclear area.


Summary

In multicellular organisms, cells that are no longer needed or are a threat to the organism are destroyed by a tightly regulated cell suicide process known as programmed cell death, or apoptosis. Apoptosis is mediated by proteolytic enzymes called caspases, which trigger cell death by cleaving specific proteins in the cytoplasm and nucleus. Caspases exist in all cells as inactive precursors, or procaspases, which are usually activated by cleavage by other caspases, producing a proteolytic caspase cascade. The activation process is initiated by either extracellular or intracellular death signals, which cause intracellular adaptor molecules to aggregate and activate procaspases. Caspase activation is regulated by members of the Bcl-2 and IAP protein families.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.