Useful Materials for Chapter 4

Cell Structure Animation
This animation helps review the various cell parts in prokaryotic cells, eukaryotic cells, animal cells, and plant cells. If found it useful for remembering the various functions of the parts that we had learned in biology before. You can click on the different parts for more information and there is a short quiz at the end that will help you to recognize whether or not you should review some more.


Virtual Cell Animations
This is a link to a free app that you can download on your iPod touch/iPhone/iPad. It includes animations on topics such as photosynthesis and cell transport. Unfortunately, I was unable to download it. So, if you do let me know what it's like! There is also another free one called 3D Cell Simulation and Stain Tool. Here is a screenshot: 

Tay-Sachs Disease

Tay-Sachs is an autosomal-recessive genetic disorder for which there is no treatment or cure. It is caused by a lack of an enzyme called Hex-A, or hexosaminidase A. This enzyme is necessary for the break down of fatty wastes in the brain's nerve cells. When there is an absence of this enzyme, the fatty waste substance (GM2 ganglioside) builds up in the cells, causing damage to the nervous system to point at which the individual with Tay-Sachs dies. The Tay-Sachs causing gene is found on chromosome 15. Tay-Sachs is an inherited disease, for which anyone can be a carrier. About 1 out of every 250 people in the population are carriers for Tay-Sachs. If both parents of a child are carriers, there is a 25% chance that the child will be born with Tay-Sachs. Certain populations, such as French Canadians and Ashkenazi Jews, appear to have increased risk of being carriers of Tay-Sachs.

There are three forms of Tay-Sachs: infantile, juvenile, and late onset. Only one of the forms can be present within one family. The most common form is classic infantile Tay-Sachs, for which symptoms develop around 6 months of age, causing the affected individual to die by the age of 5. The symptoms involve a slowing down of development, as mental and motor capabilities decrease. Eventually, the child becomes unresponsive to their environment. This disease is diagnosed either by a blood test to check the child's Hex-A levels or by identifying a cherry-red spot on the child's retina, which is classic for infantile Tay-Sachs.


For more information look at these articles that I referenced: http://www.ntsad.org/index.php/tay-sachs
http://www.tay-sachs.org/taysachs_disease.php

Endocrine Reviews: Defective Protein Folding

Beyond the Signal Sequence: Protein Routing in Health and Disease
This article focuses on the various diseases that originate from improper protein folding. The intracellular routing for many proteins is controlled by a sensitive QC, quality control, system. This system recognizes structural proteins as well as destroys defective molecules. Abnormal proteins are capable of interfering with normal cell function and can lead to cell death. Diseases that are caused by abnormal proteins usually involve the inability of a protein, or protein complex, to carry out its normal function or when a protein is incorrectly folded. Another cause is when proteins are not properly positioned within a cell.
One disease that results from improper protein folding is nephrogenic diabetes insipidus (NDI). This disease can either be inherited or acquired. The kidneys are unable to concentrate urine, even if there are normal levels of the antidiuretic hormone vasopressin present in the plasma. Vasopressin aids the body by regulating water loss and retention, by reabsoprtion of water from urine and by fusing vesicles that hold aquaporin-2 (AQP2) water channels. This prevents an increase in the water permeability within the ducts.  NDI can be caused if there are mutations in the vasopressin type 2 receptor (V2R) gene or in the AQP2 gene. The X-linked version of NDI is caused by mutations to the VR2 gene while the more rare, non-X linked version is caused by mutations to the AQP2 gene.
In VR2 mutations, more than 90% were unable to perform effective intracellular transport due to improper folding. There may also be an accumulation of VR2 in the ER. In AQP2 mutations, proteins are incapable of proper trafficking, causing the protein to remain in the ER. One type of mutation in the AQP2 has resulted in an inherited NDI that is autosomal-dominant.

Chapter 3: The Chemical Basis of Life (Macromolecules)

Valine

Alanine

Proteins

There are different types of proteins with various functions. These include (but are not limited to!): motility, receptor, membrane transport, enzyme, and catalyst proteins.
Amino acids are held together by peptide bonds caused by dehydration reactions. Amino acids can be polar, nonpolar, acidic, or basic. For example, glycine and proline are non polar, and glutamate is acidic. The structure of protein determines its function
There are four levels of proteins structure:
Primary Structure: This is the sequence of amino acids. Protein does not stay in a linear state due to the combination of hydrophobic and hydrophilic amino acids it contains, as the hydrophilic ones are "happy" by water while the hydrophobic ones are not. So, hydrophobic ones are protected while hydrophilic ones are exposed.
Secondary Structure: Amino acids interact with neighboring amino acids, forming hydrogen bonds, to bend and twist the protein chain. Some have distinctive shapes, causing them to be named (alpha helix or beta strand). The shape is stabilized by hydrogen bonds using "local folding" as specific parts of the chain can fold.

Alpha Helix

Beta Strand

Tertiary Structure: This is the overall three-dimensional shape of the protein. Non-polar (hydrophobic) parts are on the inside and polar (hydrophobic) on the outside. Ionic bonds (such as between acids and bases) as well as hydrogen bonds help to stabilize. R-groups are what determine stability.
All proteins exhibit primary, secondary, and tertiary structure. Folded proteins are functional but they can denature and become inactive or unfolded. Denaturation can occur due to an increase, in heat, pH, or salt levels.
Quaternary Structure: This is when two or more proteins chains join together in a complex protein. This level of strucutre may or may not be present in a protein.
Proteins often have non-protein components, such as the heme group in hemoglobin. This group is an iron-containing group to bind gases such as oxygen.


Nucleic Acids
Nucleic acids are polymers of building blocks called nucleotides. The two types of nucleic acids are DNA (deoxyribnucleic acid) and RNA (ribonucleic acid). DNA stores hereditary information, including all information for proper cell function. RNA helps in assembling proteins. Nucleotides are composed of a 5-carbon sugar, 3 phosphate groups, and a nitrogenous base. 4 carbons of the sugar are part of the ring while the 5th is branched from the ring. All nucleotides have a 3' hydroxyl group and the phosphates are linked at the 5' carbon. The nitrogenous base is linked at the 1' carbon. In a DNA nucleotide, the 2' carbon has simply a hydrogen while a RNA nucleotide has a hydroxyl group at the 2' carbon.
A nucleoside consists only of the sugar and nitrogenous base. A nucleoside with one phosphate group is called a nucleoside monophosphate. If it has two phosphate groups it is a nucleoside diphopshate, and if it has three phosphate groups it is a nucleoside triphosphate.
There are 4 nucleotides used to construct DNA and 4 to construct RNA. The nucleotides of DNA are adenine (A), thymine (T), cytosine (C), and guanine (G). The nucleotides of RNA are adenine (A), uracil (U), cytosine (C), and guanine (G). They differ in their nitrogenous bases. There are two basic groups of nitrogenous bases: purines and pyrmidines. Purines consist of two rings while pyrimidines have only one ring. 

The polar functional groups in the nitrogenous bases result in hydrogen bonds forming, which is what creates the double helix structure of DNA. The two strands are antiparallel, linked by phosphodiester bonds, which are covalent bonds specifically found in nucleic acids. This type of bond is analogous to a peptide bond in proteins. Nucleotides are linked to the next using a dehydration reaction. A and T bind while C and G bind in DNA. In RNA, A binds with U and C binds with G. A sugar-phosphate backbone is created that gives the skeleton for the molecule. DNA has opposite ends, called 5' and 3' ends, based off of which side of a sugar is facing what end.

Due to the double-stranded nature of DNA, the nucleotide sequence of one sequence is complementary to the other chain.
Differences between RNA and DNA:

• RNA has ribose sugars, DNA has deoxyribose sugars
• RNA exists as single strands, DNA has a double-helix structure
• Uracil replaces thymine in RNA
• RNA is synthesized from a DNA template
• At the 2' carbon, there is a hydroxyl group attached in RNA but only a hydrogen atom in DNA

DNA Double-Helix

Helpful Links

Click here for a link to a site that helps you remember the functional groups as well as learn to identify them. I especially liked the "U-Draw Functional Groups" animation. It basically gives you different molecules. You can draw on it and circle the functional groups. Then, you can hit "check" to see if you were able to find them all.

This video explains purines and pyrimidines. It made the structures clear and explain why and how they bind.


Article
http://www.ncbi.nlm.nih.gov/pubmed/21928440
This article pertains to this chapter because it is discussing a protein that may have anti-cancer, anti-HIV, and hemolytic properties. It is unknown whether this depends on the lipid-bilayer of cell membranes or the chiral receptors. A test was done using the enantiomer of the protein, which resulted in the exclusion of a chiral reception, indicating that the phospholipid bilayer is what has an impact on the effectiveness on this drug. This plays into macromolecules, as it includes both proteins as well as lipids (of the cell membranes).

Enantiomer in Thalidomide Causes Birth Defects

http://pubs.acs.org/cen/coverstory/83/8325/8325thalidomide.html

Thalidomide was a drug used from 1957 to 1961 to reduce nausea and insomnia in pregnant women. It was later discovered that women who took this medication during pregnancy were giving birth to babies with severe deformities. Now, there is clinical interest in the drug for treatment in conditions such as leprosy due to its anti-inflammatory effects. Female patients who are prescribed thalidomide are frequently tested for pregnancy while using the drug. It also has antiangiogenic and immunomodulatory properties  that can be effective against certain cancers, such as multiple myeloma. 

                                                 The Enantiomers of Thalidomide


Thalidomide had been available as a racemate, which has both "left and right-handed" enantiomers of the molecule. Enantiomers may have very different biological functions, but in thalidomide, the enantiomers undergo "rapid chiral inversion". Thus, even if only the "good" enantiomer was present, it would have converted to the "bad" enantiomer, still resulting in birth defects.



      A Birth Defect Caused by Thalidomide

Chapter 2: The Chemical Basis of Life

Summary
This chapter mainly consists of basic chemistry which lays down a foundation for learning more intricate biology topics later on. All life-forms have matter, which is composed of atoms. Atoms are composed of subatomic particles (electrons, neutrons, and protons). Each specific type of atom is called an element, which are pure substances. The protons and neutrons of an atoms are confined to the center of the atom, at the atomic nucleus while the electrons are found in orbitals at varying distances from the nucleus. The number of neutrons and electrons in an atoms are equal, except for in the case of ions. Orbitals occupy "energy shells" that are numbered. The first energy can hold up to 2 electrons and each subsequent shell can hold up to 8 electrons. The electrons in the outermost electron shell level are called valence electrons. Atoms tend to be the most stable when the maximum number of valence electrons has been filled. Each elements has an atomic number, which is the number of protons it has. For example, helium has an atomic number of 2 and thus, it has 2 protons. The periodic table is arranged by atomic number and its groups or columns show the number of valence electrons the atoms in that group have. A Dalton is a unit of measure for atomic mass, and one dalton is equal to 1/12 of the mass of a carbon atom. A mole has an equal number of particles to the number of atoms in 12 g of carbon. Isotopes are forms of an element that differ in the number of neutrons they contain. For example, Oxygen-17 has 8 protons and 9 neutrons while Oxygen-16 has 8 protons and 8 neutrons. Hydrogen, oxygen, carbon, and nitrogen make up about 95% of the atoms in living organisms. Trace elements make up less than 0.001% of atoms, but are essential for normal bodily functions.


Molecules are formed when two or more atoms bond together and compounds are molecules composed of 2 or more elements. There are three types of bonds: covalent, ionic, and hydrogen. In a covalent bond, atoms share a pair of electrons. These are the strongest type of bond since the shared electrons acts as though it belongs to each atom. The octet rule states that most atoms are stable when the outer shell contains 8 electrons, with hydrogen being the exception. If the electron is more strongly attracted to one atom, that becomes slightly negative while the other becomes slightly positive, resulting in a polar covalent bond. Nonpolar covalent bonds have a relatively equal sharing of electrons. Hydrogen bonds are the weakest type, resulting from attraction between a polar molecule to an electronegative atom. Ionic bonds occur from the exchange of electrons, resulting in ions. A chemical reaction is when one or more substances are converted into other substances. The reactants become products. These reactions require an energy source, a catalyst, and a liquid environment in order to occur. They usually eventually lead to equilibrium.


A solution is made up of a solvent (liquid) and solutes (dissolved in the solvent). Water acts as the solvent in aqueous solutions, dissolving ions and molecules that have polar covalent bonds. Hydrophillic molecules readily dissolve in water while hydrophobic molecules do not dissolve in water. Water occurs in 3 states of matter: solid, liquid, and gas. Changes in the state of matter require an input of energy. The heat of vaporization is the amount of heat required in order to vaporize 1 mole of a substance, which is high in water. The heat of fusion is the amount of heat energy that has to be released from a substance to convert it from a liquid to a solid state, which is also high in water. Colligative properties are determined by the solutes, including the temperature at which a substance freezes or vaporizes. Water has various functions including: surface tension, cohesion, adhesion, participation in chemical reactions, providing force or support, evaporative cooling, and removing toxic wastes.


Acids are molecules that release H+ in solution while bases lower the H+ concentration, either by releasing OH- or binding H+. A pH of 7 is neutral, above 7 is is alkaline, and below 7 is acidic. A solutions's pH can affect how/if ions or molecules dissolve in water, the rate of chemical reactions, the shape and properties of molecules, and the capability of ions and molecules to bind to one another. Buffers help maintain a constant pH and buffer systems   can adjust pH by generating or releasing H+.


Helpful Links

This video explains the concept of a mole. While it is supposedly simple, I had trouble understanding it. So, this explains it pretty thoroughly. It's from Khan Academy and in case you didn't know, it pretty much has free tutorial videos or all sorts of subjects. Here's the link: Khan Academy.


Click here to see an animation of hydrogen bonds and water. You can scroll through by clicking on the bottom left. It basically tells you why water molecules have the properties that they do, such as why it is a polar molecule. There is also a pH animation to help you understand the different properties of acids and bases.


Article
http://www.ncbi.nlm.nih.gov/pubmed/21910123
This article talks about the desolvation of 2 hydrate solvates in a study on the compound finasteride, which is held together by water through hydrogen bonds in order to form channels for the solvent. When desolvation occurs, both the solvent and water simultaneously become obsolete, with no change in mobility of the water molecules. This is relevant because it involves the study of the affect of hydrogen bonds and solvents on a medication used to treat enlargement of the prostate gland.

Isotopes in Sea Cow Fossils

Fossil Sea Cow Teeth Reveal Steamy Ancient Earth

Sea cows consist of a group of mammals that includes manatees and dugongs. The fossils of sea cows allow for a good climate record since they are cold-blooded and thus their chemical makeup was not influenced by changing temperatures. A study on the fossilized teeth of sea cows' teeth suggest that the Earth was warm and wet approximately 50 million years ago. The biologists used variations in oxygen isotopes between sea cows from 50 million years ago and present to discover more about ancient Earth's environment. The two most profuse oxygen isotopes of seawater molecules are oxygen 16 and oxygen 18, which marine mammals absorb into their bodies. Enamel scrapings were collected from many sea cow fossils to measure their oxygen isotope ratios. These biologists found that the oxygen 16 to oxygen 18 ratio of sea cows that lived in low latitudes about 50 million years ago had an oxygen 16 concentration that was higher than expected. Rainfall has more oxygen 16 than oxygen 18, suggesting that the low latitudes that these sea cows were living in received more rainfall than they do today. This also suggests a warmer atmosphere during this time period since it would allow for more water vapor to be held. As the Earth's climate is becoming hotter due to global warming, these findings could help scientists predict how water cycles may change in the future.

                                                  Prehistoric Pygmy Sea Cow Illustration