Carbohydrates

The first building block of life is called carbohydrates or sugars. You might also hear them called glycans. They are made up of a carbon chain with a single oxygen binding the carbons into a ring-like structure that looks like a stop sign. Usually, each carbon has a hydroxyl (OH) group on it. They can come in different carbon numbers. Ribose makes up RNA and DNA and it has 5 carbons; whereas, glucose, fructose and galactose are made up of 6 carbons bound into a ring-like structure.

A monosaccharide is the most basic structure of carbohydrates as it is just one single carbohydrate. There are several monosaccharides we will deal with in biology. They are Glucose, Galactose and Fructose. RNA and DNA are made up of a 5 carbon monosaccharide called Ribose. The only difference between RNA and DNA is the number 2 carbon has a single hydrogen for DNA instead of the OH group. This is why it is called deoxyribose. Deoxy means one less oxygen. The entire DNA structure is made up of nucleotides built of nucleic acids attached to deoxyribose sugars.

All RNA is made up of ribose sugars. The key attribute of the extra oxygen on the number 2 carbon for RNA is that it prevents the RNA from wanting to become double stranded like DNA. It causes an electrical force that wants to repel double stranding. This is one of the main reasons DNA can be double stranded and RNA will be single stranded. That single missing oxygen allows DNA to bind in double strands without causing electrical resistance between the atoms.

The carbohydrates we ingest for nutrition come from three basic monosaccharides with glucose, fructose and galactose. These three carbohydrates have the exact same chemical formula of C6H12O6. They are isomers of each other as their atoms are slightly arranged in different configurations. The main difference due to their differences in structure is their different level of sweetness. Glucose is sweeter than Galactose and Fructose is sweeter than glucose. Many of these sugars come together to form Disaccharide compounds.

Disaccharides are compounds made up of two monosaccharides. There are some basic formations you will find with Sucrose, Lactose and Maltose. Sucrose is what we call table sugar, and it's made up of one glucose bound to one fructose. Lactose is made up of one Glucose bound to one Galactose. Maltose is made up of two glucose bound together. These are the basic disaccharides. There is an enzyme in the digestive tract called Lactase which is designed to break the bond between the Glucose and Galactose in the Lactose disaccharide found in milk. People who lack this enzyme can not break that bond and can not digest lactose.

A polysaccharide is made up of long chains of monosaccharides which we call starch and cellulose. This is one of the main rigid building blocks in plant structures that gives them form. The difference between starch and cellulose is the bonding patterns between the two. Cellulose is also called fiber, and fiber is not digestible which makes it very important for digestive health.

You will often hear the term simple carbs and complex carbs. The simple carbs are the monosaccharides and disaccharides. They break down quickly and get into the bloodstream quickly to drive up the sugar levels. The complex carbs are the starch and fiber. The starch takes much longer to break down which allows the sugar to slowly digest into the bloodstream over time.

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Lipids

Lipids are hydrocarbons and they make up oils, fats and waxes. They have a good role in biology, but they can also have a bad role in biology. Some fats do not help while others are essential. We call them essential fatty acids. The key to a fatty acid is the Carboxylic Acid group on the end of the long chain hydrocarbon.

Fatty acids come in a few different kinds. The first is saturated fats. With saturated fat, there are no double bonds in the carbon chain. Saturated fats are the bad fats. They are fully saturated with hydrogens. The second is the unsaturated fat. This has at least one double bond in the carbon chain. Unsaturated fats come from plants, oils, nuts and seeds. They are called the good fats. A polyunsaturated fat has more than one double bond. All essential fats are polyunsaturated.

Most saturated fats are bad and come from meats while unsaturated fats come from mostly plants. Trans fat is really bad as they are artificially made. If you remember the concept of a trans configuration around a double bond, they have the functional groups on the opposite sides of the double bonded carbons. They are very bad as the human body does not process them correctly.

The Glycerol element is a 3-carbon structure that is used to bind 3 fatty acids to it. It's a form of fat storage. When we consume too much fat, they will get bound to the glycerol to form a triglyceride which stores that extra fat. The build up and storage of bad fats using triglycerides leads to cardiovascular disease.

So far we only focused on the consumption and storage of fatty acids, but we will now look at the use of these fatty acids that make them beneficial. The most important role of fatty acids is to make up phospholipids. The phospholipid takes the Glycerol element and binds 2 fatty acids to it, one being a saturated fat and the other being an unsaturated fat. The third carbon then binds to a phosphate group creating a compound that has phosphate at one end and the tails of the 2 fatty acids at the other end. This makes the phosphate head hydrophilic (water loving). The fatty acid end will be hydrophobic (water hating).

These phospholipids work together to make the phospholipid bilayer of the cell membranes. The cell membrane takes two rows of phospholipids and places them with the phosphates away from each other and the fatty acid ends toward each other. This allows the cell to separate the water outside the cell from the water inside the cell. This phospholipid bilayer will be one of the most critical concepts of biology.

When a phospholipid gets damaged, some of the fatty acids will be dislodged by the trauma. There is an enzyme called phospholipase A2. This will trigger a pathway called Arachidonic Acid which plays a key role in tissue inflammation and blood clotting.

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Nucleic Acids

There are 5 basic nucleic acids that make up human DNA and RNA. They are synthesized from reactions in the cells. The 5 nucleic acids are Adenine, Guanine, Cytosine, Thymine and Uracil. They are made up of nitrogen-based structures and are often called the nitrogen bases. They get attached to a ribose sugar and a phosphate group to form what is called a nucleotide. These nucleotides get chained together to form strands of DNA or RNA.

The 4 nucleic acids used in DNA are Adenine, Guanine, Cytosine and Thymine. Thymine is replaced with Uracil in the RNA. The only difference between the actual nucleic acids is the Thymine and Uracil. The other difference is the ribose vs deoxyribose we looked at earlier.

The nucleic acids are synthesized from pathways and enzymes to create the bases that make up the nucleic acids. They are made from the process of purine and pyrimidine synthesis. There are disorders of the process of synthesis of making nucleic acids. There is also a disorder for people who don't break down the nucleic acids correctly. One such example is gout, which is the failure of the body to remove the Uric Acid created by the breakdown of purine nucleic acids. This allows the uric acid to build up in the joints and cause inflammation and damage.

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Amino Acids

There are 20 basic amino acids. They make up all proteins and all life on earth. The basic structure for amino acids is the same. They have an alpha carbon which is attached to a carboxylic acid group, an amino group and a side group that changes with each amino acid. The only difference between the amino acids is their side group.

The side group is critical and it makes up the basic chemical attributes of that amino acid. Some of them are non polar meaning they won't like water. They will be hydrophobic which is water hating. Some amino acids will be polar which makes them hydrophilic which is water loving. A few will have neither a positive or negative charge. Understanding these attributes of amino acids will be very important later when we get into the building of proteins and their folding.

We ingest amino acids in the form of the protein that we eat. All proteins are made up of long chains of amino acids. Our cells will take in the fragments of proteins we ingest and break them down. The process of the cell breaking down the protein into its basic amino acids is called catabolism. This is done inside a cellular organelle called the lysosome. Inside the lysosome are enzymes that will break down the proteins into amino acids. The cell will then take those amino acids and use them as building blocks to make new proteins. There is also another cellular process by which the cell can recycle proteins it creates to break them down into amino acids and recycle them for use. This is called autophagy. This occurs during cellular stress like starvation. This causes the cell to break down and recycle unused proteins to get the amino acids to build new necessary proteins.

Some of the amino acids our cells need can be synthesized by the body. The amino acids we can't make ourselves require us to eat food to get them. These are called essential amino acids. After the cell has broken down the proteins into amino acids, it can use them to make new proteins that it needs. This is done by the cellular organelle called the ribosome. These ribosomes work very much like a factory for building proteins. They receive a messenger RNA that is the blueprint for that protein. They read that blueprint and use it to take amino acids and chain them together into a long chain called a peptide.

After the peptide chain is constructed, it will fold into a 3 dimensional structure of the protein. It uses those many hydrophilic, hydrophobic and electrical forces of the amino acids to fold itself. All the hydrophobic amino acids will fold inward away from the water inside the cell. The hydrophobic amino acids will fold outward toward the water as they like the water. The electrical forces will create bonds between specific amino acids to hold everything together.

The structure of a protein determines its function. If even a single amino acid is coded wrong, it can dramatically change the structure of the protein and thus its function. That is exactly what happens in the rare genetic disease Sickle Cell Anemia. A single mutation in the DNA codes the wrong amino acid, turning it from hydrophilic to hydrophobic. This changes the entire behavior of that new protein leading to disease.

An enzyme is a protein that facilitates a chemical reaction. All enzymes end in -ase so you will quickly recognize them by their names. A good example is Lactase which is an enzyme that helps break apart Lactose. Many chemical processes in biology can be very slow. An enzyme can lower the energy necessary to start a reaction or it can speed up the time it takes. Some enzymes can facilitate a chemical reaction many fold.

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Cellular Respiration

Cellular respiration comes in 3 steps: Glycolysis, Krebs cycle and Electron Transport Chain. The entire goal of this process is to break down glucose and produce energy in the form of Adenosine Triphosphate (ATP). It produces on average about 38 ATP from a single glucose.

Adenosine Triphosphate is the energy currency of the cells. It's made up of an adenine nucleic acid just like that which is used in DNA or RNA. It even includes the ribose and the phosphate group. That is the basic structure of the Adenosine Monophosphate (AMP). Then you add on two more phosphate groups. Each phosphate that is added requires an input of energy to attach the phosphate group. This becomes a medium of energy storage. By releasing a phosphate, the energy stored in the molecule can be released.

The adenosine can have between 1 and 3 phosphate groups. The most energetic is the Adenosine Triphosphate (ATP). Once the first phosphate group is removed, it becomes adenosine diphosphate (ADP). This then can become energy for other cellular processes. The ADP is used in activation of platelets. Once the second phosphate is removed, it becomes adenosine monophosphate (AMP). The AMP acts as a low energy sensor for the cell.

There are different kinds of energy used in the cells. This means the cells need a method to exchange one type of energy currency for another. Just like you go to the bank to exchange dollars to euros, the cell can exchange one form of energy for another. There are different enzymes in the cells that are responsible for conversion of the energy from one form to another.

The other form of energy in the cell uses a guanine in place of the adenine. This makes Guanosine Triphosphate. Again, this can exist in three forms with 1 to 3 phosphates attached to the guanine. There are processes in the cell by which guanine is used. Different processes in the cell will cost different types of energy. Those processes in the cell that use the Guanine form of energy are called the Second Messengers.

Glycolysis is the first step of cellular respiration. It occurs in the cell cytoplasm. It requires no oxygen to conduct the process of glycolysis. This is called an anaerobic process as it takes no oxygen. Glycolysis uses a series of enzymes to break sugar in half from glucose, fructose or galactose C6H12O3 into pyruvate (C3H3O3). We could spend a ton of time going over all these enzymes, but you really only need to know the process and not every enzyme or step in the process. There are genetic disorders where one of these enzymes does not get made. One such disorder is Pyruvate Kinase Deficiency. This is missing that very last pyruvate kinase enzyme which makes the pyruvate. The process of glycolysis costs 2 ATP as an input energy to get the process working. As the glucose is broken down by enzymes, it makes 4 ATP, 2 NADH and 2 pyruvate molecules (C3H3O3). The NAD is an enzyme which is responsible for transporting hydrogen ions. This will be important later in the Electron Transport Chain.

This process of glycolysis is used by Red Blood Cells (RBCs) so as not to use oxygen. The RBC is built to bind and deliver oxygen to the tissues of the body. It only makes sense that these cells would not consume oxygen in the process of their delivery. They still need energy so they use just basic glycolysis to get that energy. RBCs will only do glycolysis and skip the rest of the cellular respiration cycle.

If there is oxygen, the pyruvate goes into Krebs cycle to be broken down further. If there is a lack of oxygen, then the pyruvate will ferment into lactic acid. Lactic acid is what makes your muscles hurt when you work out. This is caused by the deprivation of oxygen to the muscle during an intense workout which causes the pyruvate to ferment into lactic acid.

Cancer cells will use glycolysis to live in low oxygen tissues where there is no oxygen. The reprogramming of cellular respiration is one of the hallmarks of cancer. This causes lactic acid to be a byproduct of the cancer cells. Many cancer cells will then ramp up the level of their glucose intake so they can make all the needed energy using basic glycolysis. This allows us to use the high glucose intake of cancer cells to develop a scan that can detect this using glucose tagged with an isotope.

After the pyruvate has been created by glycolysis, the pyruvate and NADH will travel into the mitochondria which is the powerhouse of the cell. The process of the Kreb cycle will require oxygen. This happens inside the inner part of the mitochondria.

First the pyruvate is modified to become acetyl Coenzyme A (acetyl CoA) before it undergoes breakdown into hydrogen ions and carbon dioxide (CO2). Once the acetyl CoA is created, it will be broken down by the use of 2 ATP. This process will create 2 ATP along with 6 more NADH and 2 FAD(H2). The FAD enzyme is another enzyme that binds and transports hydrogen ions.

At this point, the glucose has fully been broken down and all the carbons, and oxygens have been released as CO2. The hydrogens are all now bound in the form of NADH and FAD(H2). These hydrogen ions will then go on into the Electron Transport Chain.

The mitochondria has an inner chamber where the Kreb cycle happens. Then there is an inner membrane that separates the inner mitochondria from the outer mitochondria. Inside this inner membrane are these little hydrogen ion pumps. The NADH and FAD(H2) will transfer their hydrogens through these pumps.

As all the hydrogens are transferred out of the inner mitochondria to the outer part, the gradient of hydrogen ions increases. Once a specific level of hydrogen concentration is reached in the outer mitochondria, it will cause these special enzymes called ATP synthase to open up and release the hydrogen ions back across the membrane into the inner mitochondria again. This requires oxygen and combines the hydrogens to the oxygen creating water.

This process causes the ATP synthase to become active. It works much like a water wheel. As the hydrogens move through the ATP synthase, they will spin a small gear-like structure. This creates the energy from the releasing of all the hydrogen ions across the membrane. It uses this energy to take the phosphates and put them back onto ADP to make new ATP. This process varies based on the amount of hydrogen gradient between the inner and outer mitochondria. The average is around 32 ATP is made by the ATP synthase. This makes up the bulk of all the ATP created during cellular respiration. This is where the mitochondria gets its nickname as the power plant of the cell.

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