Half-Hour Background Info

This is a general set of information that I tried to set up in a decent flow. It’s the same posts as the ones on the Basic and Background Science page, just in a complete page that goes from basically the bottom up.

Elements are everything

Elements are the building blocks of everything, including our DNA and proteins. The elements are represented on the periodic table. Common atoms used in the stuff in our body are carbon, nitrogen, oxygen, and hydrogren. Also used are sulfur, phosphoryus, sodium, chlorine, and magnesium.

Elements can build into “stuff” by connecting at the atomic level and building up. An atom isn’t really the smallest kind of particle, but it is the smallest unit of matter that has a definably unique identity. This uniqueness comes in the number of protons, or positively charge particles in the atom.  Atoms also have neutrons (particles with no charge) and electrons (particles with negative charge). Neutrons and protons exist in the center, or what we call the nucleus, of the atom, and the electrons exist in a “cloud” around the nucleus. The number of protons an atom has determines what element we identify it as. For example, the atomic number of carbon is 12, which means that carbon has 12 protons.

Once these atoms start to “build up,” we call it a molecule. We call molecules from our body, such as DNA and proteins, biological molecules. DNA and proteins are both huge kinds of molecules, and are often called biological macromolecules.

DNA→ RNA→Protein

First, let’s dive into the cell. Our bodies filled with organs, made from tissues, made from cells. Within cells are different little compartments that do their own function for the benefit of the whole cell. DNA is stored in the nucleus, which is like the brain of the cell. The first video here is a quick explanation of cells

Read below for a written explanation of DNA and protein. Or watch these videos. The top 2 videos is are fun raps, and also a great explanation of how DNA leads to protein. Below that is a visually beautiful and thorough explanation of DNA and protein, but it’s a tad dry.

DNA: DNA is the genetic code. It’s stored information made of sugar building blocks (bases) that have a phosphorus atom attached as a phosphate group, with a base attached. The sugar is essentially structurally the same for every part of DNA. The unique part of the nucleotide comes from the nitrogen-containing base. There are four that naturally occur: adenine (A), thymine (T), cytosine (C), and guanine (G). One strand of DNA will have a backbone that’s a long chain of connected phosphates. To each phosphate a sugar is attached. To each sugar a base (A, G, C, or T) is attached. Again, that’s one strand of DNA. Most eukaryotic DNA is double stranded. This occurs by the pairing of the bases. Adenines are weakly bonded to thymines and cytosines are weakly bonded to guanines. So on the DNA would be in the order of AGCT. Now, matching each of those bases with its pair would mean the other strand, going down the same direction as the opposite strand, would have the sequence TCGA. This base pairing is also referred to as complementation, so that when one DNA strand is made that pairs up with another DNA strand, they are referred to as each other’s complement. Double-stranded DNA twists to form a helix, and then bundles and winds tighter and smaller until it forms a compact structure called a chromosome. A genome is a complete set of all the DNA in an organism, and is typically divided up into individual portions we call chromosomes. So different genes can exist on different chromosomes. DNA typically exists in the nucleus of the cell, but has also been found in mitochondria and chloroplasts.

RNA: There are many different kinds of RNA, but we only need to go over two kinds now, messenger (mRNA) and transfer (RNA). mRNA is the information in process, and is essentially what parts of the genetic code (DNA) the cells decides to process at that time. It’s like having a multi-volume set of thick recipe books (the genome made of DNA), and our friend wants a copy of the book’s recipe for vegetable soup. In order for her to use the recipe, we need to transcribe it or make a copy she can understand. Instead of copying the entire recipe book for her, we instead just copy the recipe she needs, for vegetable soup. Now let’s say that our friend is used to the metric system of measuring volume in milliliters, but our recipe book lists volumes in cups and pints. We know how to convert the recipe to the volume measurements our friend understands, but she doesn’t, so we do it for her. This an analogy of why mRNA is made. There’s so much genetic information stored in our genome that it would be wasteful for cell machinery to make all of the proteins it codes for every time protein is made. Not all proteins are needed all the time. Some are needed much more often than others. To be efficient, the cell only makes a copy of what it needs when it needs it, which is why RNA is transcribed. RNA is made of sugars very similar to DNA, but has an extra hydroxyl (an oxygen-hydrogen group). When transcribed into RNA, the thymine base is substituted for a uracil, the RNA equivalent, so that AGTCTT becomes AGUCUU. The reason RNA is made instead of just another DNA copy of the gene is because that extra hydroxyl is necessary for the working activity of RNA.  It’s thought that uracil is used in RNA because it takes less energy for the cell to make it. It’s not used in DNA because cytosine can degrade into uracil and there needs to be some way for the cell to detect the C/U difference from thymine in order to catch and correct DNA mutations. Another feature distinguishing mRNA from DNA is that mRNA is usually single-stranded, which means that the bases don’t pair. Once DNA is transcribed into mRNA copies in the nucleus, it’s moved from the nucleus back into the cytosol, where it is placed near a ribosome, and translation (protein manufacturing) begins.

While DNA is an information store, RNA (the multiple types) can be both an information store and an active molecule in itself. tRNA does not serve the same purpose as mRNA. It has shorter sequences than mRNA, and it forms a clover-leaf like structure. It serves directly to bring amino acids to a growing peptide sequence, which we’ll cover more below.

Protein: Proteins are the workers of the cellular processes. They make things happen. At the beginning of a gene, a “Reading frame” begins. Every three nucleotides (a codon) makes an individual message to the translation machinery. These three nucleotides become their own code that calls for an individual amino acid, which is a relatively small biomolecule.  The codon is recognized by the tRNA that brings the individual amino acid to the ribosome and puts it into a position so that the amino acids can be attached to the peptide chain. Twenty amino acids occur naturally in most living organisms. SO AGT becomes AGU, which calls/codes for a methione (M). When I worked at a fast food drive in, we used short codes for our food items. So when I saw S BURR on the ticket, I knew the customer asked for a sausage burrito, so that’s what I took them. I acted like the tRNA there. Now each tRNA is actually unique to the amino acid it delivers, but there are actually a few combinations/ codons that can code for one amino acid, so the tRNA can recognize one to all of these codons. As the codons are read from the RNA sequence, the amino acids corresponding to each codon are joined to the growing protein chain one by one. The type of amino acids, the placement within the protein sequence, as well as the number of each amino acid each protein contains affects the protein identity. Each amino acid has a unique structure, causing it to have its own properties, which can add to and form the total properties of the protein. These properties affect the function of a protein. One such property is the amino acid polarity, and how that contributes to the overall polarity of the protein. Polarity can affect where in the cell the protein can exist, and thus affects what functions it may have. For example, a protein with a lot of nonpolar residues will be relatively hydrophobic, and so it won’t be stable in the cytosol. One place it could be stable is within the plasma membrane, which has a hydrophobic core because of the hydrophobic, nonpolar lipid tails. Proteins that are embedded in the membrane can serve a variety of purposes, such as forming a channel that molecules can pass through to enter the cell.

Seriously, why are so many science videos so dry. Also, the ones that try to be a little fun are also some of the best explanations for the general person.

Mitosis and Meiosis

Mitosis and meiosis are two similar processes that lead to duplication of the genome and multiplication of cells. Mitosis occurs when a somatic cell (non-sex cells, such as epidermal cells, muscle cells, etc.) divides into two new cells. This happens because our cells need to regenerate because cells have a certain lifetime. Meiosis occurs when a germ cells (such as what leads to eggs or sperm) divides to four new cells that with 1 copy each of the genome that can contribute to a fertilized egg (zygote) and lead to a new organism.

First, each human being has two copies of their genome in all of their somatic cells. These copies may actually be two slightly different forms of a gene, called alleles. During the one cycle of mitosis, these copies are replicated so that the original cell can split into two “new” cells, each with each of the two alleles for each gene.

Our germ cells are still haploid before the process of meiosis. During the two cycles of meiosis, the original germ cell makes a single duplication of the genome (so now there are four alleles of each gene, with two identical pairs). Instead of only dividing once like in mitosis, there are two different division events in meiosis. After genome duplication, the original cell divides into two daughter cells with two copies each of the genome. This is the process of the fist meiotic cycle, Meiosis I. During the second cycle, the genome doesn’t duplicate. Instead the two new daughter cells split themselves into two more new daughter cells each. Now there are four daughter cells, each with one copy of the genome. These cells become gametes, such as sperm and egg cells.

Genetic mutations:

The genetic code is replicated during mitosis. If the code is replicated incorrectly, such as a code that should be “AGCT” becomes “ACCT,” by mistake of DNA replication protein machinery, this is called a mutation. There are several types of DNA mutations:

Missense mutation: a base pair substitution that causes the amino acid to change. Any amino acid change could cause the protein identity to change, causing a change or loss in its function.

Nonsense mutation: a base pair substitution that stops protein translation prematurely, causing a protein sequence to be shorter than it should be.

Insertion: a nucleotide or base pair is incorrectly added in as an extra base pair. Could change the amino acid code of the protein.

Deletion: a nucleotide or base pair is incorrectly deleted, or just left out, of a sequence it should be in. Could change the amino acid code of the protein.

Frameshift: one or more base pairs is added or deleted, causing a the reading frame to change. This changes how the codons, changing the amino acid sequence and thus the protein.

Duplication: a gene is copied more times than it should be. This can cause an increased size of the chromosome the gene lies on, as well as a positional shift on the genome of downstream genes.

Repeat expansion: short DNA sequences that exist as repeats (such as ACGACG) are repeated more than they should be (such as ACGACG become ACGACGACGACG). This can lengthen the gene, and cause an additional, amino acid to be abnormally incorporated into the protein, potentially changing the protein function.

Several of these mutation types can cause a change in the protein sequence, and thus the protein’s properties and its functions. These types of mutations can cause the protein to be destroyed by other proteins that sense this kind of mutation. If this occurs, the cell may not have this particular protein and may be unable to perform an essential function, leading to disease.  Another potential outcome is that the protein acts abnormally and in a way that negatively affects cell functions, and thus causes disease. There are several mechanisms the cell can use to detect and fix mutations, but when these fail disease can arise.

Chemistry basics:

Polar/ nonpolar and bonding: molecules, such as small molecules like water, or large macromolecules like proteins, have properties based on their polarity. Polarity is a spectrum. A molecule can be very nonpolar, or it can be slightly polar, or very polar. Polarity is a concept based on how the electron density exists around each atom in the molecule, but it can be displayed in how it affects the molecules interactions with other molecules. Molecules associate easier with other molecules that have a similar polarity. Molecules that have large differences in polarity tend to repel each other. One example is oil and water. Oil is composed of lipids, which have very little polarity and are essentially nonpolar. Water is a very polar molecule. Many of us have observed that water and oil don’t mix; we can see oil “bubbles” clumping together in pools of water. If you oil an iron skillet and then pour water in the pan the water will form droplets. What’s occurring here is that the water is associating with itself, or forming more surface interactions with other water molecules (polar), forming the droplets, rather than spreading evenly across the oil surface on the pan and associating with the lipid molecules (nonpolar) in the oil. This phenomenon may also be referred to as the hydrophobicity/ hydrophilicity of a molecule. A molecule that can mix and associate with water is referred to as hydrophilic (water-loving), whereas a molecule that doesn’t mix with water (such as oils/ lipids) is referred to as hydrophobic. Technically hydrophobicity/hydrophilicity isn’t necessarily the same as the phobicity of  a molecule, but often the terms are used interchangably because often the more polar  the molecule the more hydrophilic it will be and the less polar the less hydrophilic/ more hydrophobic it will be.

Polarity In the Cell

A cell is a collection of organelles (which perform all the little cells functions) suspended in a fluid like substance called the cytoplasm (a polar substance), surrounded by a membrane. Typically, eukaryotes (life that’s more complex than bacteria (Prokaryotes) have a double layered membrane. The membrane is made of lipids (nonpolar), packed in sheets. Each lipid has a long carbon chain tail and a polar phosphate group head. Again, there are two layers of these forming a typical eukaryotic membrane. The tail ends face each other, and the head groups face the inside and outside of the cell. This arrangement works well as the polar head groups associate with the polar cytoplasm and shield the nonpolar lipid tails from the cytoplasm.

The differences in polarity between the cytoplasm and the membrane also display with where a protein ends up, or localizes. Proteins on needed on either side of the membrane, as well as within the membrane. So it becomes essential for proteins to have a nonpolar exterior, meaning nonpolar amino acids on the outside of the protein, if the proteins are to localize within the membrane. On the other hand, if a protein is needed to function in the cytoplasm, then polar amino acids need to be on the outside associating with the polar cytoplasm and nonpolar amino acids need to be on the inside of the protein. This is an example of how a protein folds, or is shaped, becomes important. Proteins are formed as nonfolded sequences of amino acids, but as soon as that chain begins folding begins. This folding can be a result of the environment or other proteins. Proteins are made in the cytoplasm (polar), so if nonpolar amino acids are being added to the amino acid chain, these are repulsed by the polar cytoplasm. Thermodynamic and kinetic effects can help by causing changes and folds that bury these nonpolar amino acids within more polar amino acids. Other proteins (called chaperones) can help in protein folding by helping the protein to fold correctly.

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