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The P/O ratio is determined experimentally and is a number that relates the amount of ATP generated per electron carrier. This number can vary depending on the physiological conditions. P stands for the moles of phosphoryl groups consumed to form ATP, and the O stands for moles of oxygen consumed to be reduced to water. The P/O ratio of one NADH is 2.5 ATP, and the P/O ratio of one FADH2 is 1.5 ATP. FADH2 has a lower P/O ratio because FAD has a higher affinity for electrons and donates them through the electron transport chain at complex II and contributes fewer protons to the gradient. Per glucose, 32 ATP are produced. 4 ATP are produced directly while 25 ATP are produced through NADH and 3 ATP are produced through FADH2. The total number of ATP produced can vary from 28-36 depending on the P/O ratios of NADH and FADH2 dependent on physiological conditions.

An individual developed a condition characterized by progressive muscle weakness and aching muscle cramps. The symptoms were aggravated by fasting, exercise, and a high-fat diet. After several experiments, the patient was diagnosed as having a carnitine deficiency. The symptoms were aggravate by a high fat diet, exercise, or fasting because carnitine plays a role in acyl-CoA transport in fatty acid oxidation. Without carnitine, acyl-CoA will build up when trying to process lipids. Out of the pathways in the muscle cell, lipolysis will be the least affected by a carnitine deficiency since it does not occur in the muscle cell. On the other hand, acyl-CoA formation will slow down since there will be a build up of it. Also, beta-oxidation will not be able to coccursince acyl-CoA is less transported into the mitochondria.

Thermogenin is a protein found in the inner mitochondrial membrane in adipose tissue of some animals, such as human infants and bears. The presence of this protein allows protons to flow from the intermembrane space to the mitochondrial matrix. If a lot of this protein is present, it will decrease the rate of ATP synthesis but increase the rate of oxygen consumption, which is a measure of electron transport chain activity. This is because the proton gradient cannot form if they are allowed to flow back to the matrix and cannot be built up in the intermembrane pace. The proton gradient is what powers the synthesis of ATP through ATP synthase. Oxygen consumption will still increase though since the electron transport chain will continue to pump protons into the intermembrane space in an attempt to form a gradient. Thermogenin allows for heat production without the production of ATP, so it is important to babies and hibernating bears, which don’t require much ATP.

Fatty acid synthesis is primarily carried out in the cytoplasm of liver cells and involves multiple processes: (1) Acetyl-CoA transport, (2) malonyl-CoA formation, and (3) synthesis cycles. Acetyl-CoA is produced in the mitochondrial matrix and must be transported to the cytoplasm. It is transported indirectly as citrate, which is then converted back to acetyl-CoA once outside. The enzyme acetyl-CoA carboxylase (ACC) then carboxylates the acetyl-CoA to form malonyl-CoA, the direct substrate of fatty acid synthesis. Synthesis is carried out by fatty acid synthase (FAS), an enzyme that acts as a dimer to make two fatty acid chains simultaneously. First, the cysteine amino acid on FAS is primed. Then, sequential cycles of reactions create the fatty acid, each cycle adding two carbons from malonyl-CoA with energy from NADPH. Seven cycles produce a 16-carbon chain, and all fatty acid chains produced by FAS are 16:0. Additional enzymes are then required to elongate and/or desaturate the chain to form other fatty acids. The enzyme desaturase is responsible for adding double bonds, but it is incapable of forming double bonds past the tenth carbon. Therefore, fatty acids with double bonds past the tenth carbon are acquired solely through the diet.

Fatty acid synthesis is mainly carried out in the cytoplasm of liver cells. It is not the reverse of fatty acid oxidation and involves multiple processes: (1) Acetyl-CoA transport, (2) malonyl-CoA formation, and (3) synthesis cycles. Acetyl-CoA is produced in the mitochondrial matrix and must be transported to the cytoplasm. Carbons are transported out to the cytoplasm indirectly as citrate, which is then recreated into acetyl-CoA once outside. The acetyl-CoA is then carboxylated to form malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC). Malonyl-CoA is the actual direct substrate of fatty acid synthesis. Synthesis is carried out by the enzyme fatty acid synthase (FAS), which acts as a dimer that makes two fatty acid chains at once. First the cysteine amino acid on FAS is primed, and then sequential cycles of reactions create the fatty acid. Each cycle adds two carbons from malonyl-CoA using the energy from NADPH. Seven cycles produce a 16-carbon chain, and all fatty acid chains produced by FAS are 16:0. Elongation and desaturation to create other fatty acids are carried out by additional enzymes. Double bonds are added by the enzyme desaturase; although, human enzymes cannot form double bonds past the tenth carbon. Fatty acids with double bonds past the tenth carbon are acquired solely through diet.

Fatty acids are central molecules in lipid metabolism. They carry most of the energy in a triacylglycerol and oxidation of them releases energy. The oxidation of a fatty acid is a five-part process that starts in the cytoplasm and ends in the mitochondria: (1) acyl-CoA formation, (2) acyl-CoA transport, (3) beta-oxidation, (4) citric acid cycle, and (5) oxidative phosphorylation. While the last citric acid cycle and oxidative phosphorylation steps are the same as in slow respiration, the other three steps are unique to fatty acid oxidation. Acyl-CoA is formed in the cytoplasm by acyl-CoA synthesis, which requires two ATP. The acyl-CoA is then transported into the mitochondrial matrix for oxidation. This transportation is carried out by the carnitine acyltransferase, and once inside, the acyl-CoA cannot be transported out. Beta-oxidation involved sequential cycles of four reactions where electrons are transferred to FAD and NAD+ and carbons are removed as acetyl-CoA, a two-carbon molecule. These four reactions continue to cycle until the whole fatty acid chain is oxidized, two carbons at a time. One thing to note is that the oxidation of unsaturated fatty acids requires additional enzymes and varies based on the position of the double bonds. Fatty acids with double bonds are less reduced than saturated fatty acids and therefore yield fewer ATP per carbon.

The reason why the liver must process the material is because triacylglycerol’s hydrophobic nature makes it difficult to transport and store in the body. Animals attempt to solubilize these molecules through the biosynthesis and distribution of lipoproteins. Lipoproteins come in different types that vary in the percent and type of lipids and proteins that compose it. Lipoproteins have a phospholipid membrane with cholesterol and proteins embedded in it, and inside, they carry cholesterol esters and/or triacylglycerols. Triacylglycerols are then stored in adipose cells, or adipocytes, which are the location of fat storage in animals. Triacylglycerol synthesis is known as lipogenesis and is the creation of triacylglycerol from glycerol and three fatty acids. It occurs in the liver and adipose cells. On the other hand, triacylglycerol degradation is known as lipolysis and is the breakdown of triacylglycerol to glycerol and three fatty acids. It occurs only in adipose cells and involves three enzymes in the process. The fatty acid products then exit the cells and bind to albumin in the blood.

Lipids are crucial biomolecules in our body. Their main functions are involved in energy storage, membrane structure, and signaling. Because the fatty acid chains are dominant in the structure and are made up of primarily hydrogens and carbons, lipids are significantly nonpolar. Bond between carbons and hydrogens are nonpolar because of their relatively similar electronegativities. The most important interactions that contribute to the properties of a lipid are van der Waals forces. The simplest lipid formed by fatty acids is triacylglycerol, also known as triglyceride. It is a glycerol bonded to three fatty acid chains, and the bonds between the two are formed by dehydration between glycerol hydroxyl groups and fatty acid carboxyl groups. The fatty acid chains are virtually always different. Triacylglycerol transport and storage revolve around the liver and adipocytes, which are the tissue involved in fat metabolism. Material from the digestive system or body cells enter the liver, where biosynthesis of lipoproteins, fatty acids, and cholesterol occur. These synthesized products are then distributed to adipose cells for storage or are distributed to the body cells for energy use.

It's possible that we will be able to create "enhanced" humans through Cas9 genome editing sometime in the near future; however, if I was given the option years from now to genetically modify my child to be taller, I wouldn’t opt for the height-enhancement of my child. A child is their own being, and I think there’s a beauty to the fact that parents cannot decide who or what their child is. It’s not the parents’ place to decide or control how their children will be before they can for themselves. A part of parenthood is about unconditional love for your kid, regardless of if they’re short or tall, and there seems to be something off about engineering your child to be what is considered favorable to you or to the world. A purposeful height-enhancement may damage a child’s view of their parents’ love. If a child knew that some part of them was pre-decided by their parents, it may convince them that their parents only love them because they decided what kind of child they wanted beforehand. Additionally, there is a chance that the genes altered to enhance their height were pleiotropic, which would mean we may have altered other phenotypes that would have been beneficial to the child.

It was once unexplained why European hair color varies so greatly, from black to blonde to even red. This article is about how scientists have discovered over 100 genes linked to European hair color. This article clearly explains that hair color is polygenic, which is a concept we discussed in class. A trait is polygenic when it is controlled by two or more genes, which causes them to be continuously variable. Here, we can see hair color is controlled by a plethora of genes throughout the genome that cause European hair to vary as much as it does. According to this article, the researchers who discovered these genes hope for their work to contribute to finding treatments for pigment disorders. They believe that some of the genes that they found affect hair color may also be associated with diseases such as Crohn’s disease and skin cancer. In other words, they believe that some genes that influence hair color are pleiotropic, which is a also a concept discussed in class. Pleiotropy is when a single gene affects several traits.