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Biochemistry and Molecular Biology: How Life Works

YEAR: ???? | LENGTH: 36 parts (30 minutes each)  |  SOURCE: TGC

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One of the triumphs of modern science has been our ever-improving understanding of how life works—how chemical reactions at the cellular level account for respiration, digestion, reproduction, locomotion, and a host of other living processes. This exciting subject is biochemistry—and its allied field of molecular biology. In the past century, progress in these complementary disciplines has been astonishing, and a week rarely passes without major advances in medicine, physiology, genetics, nutrition, agriculture, or other areas, where biochemistry and molecular biology are shedding new light on life.

episodes:

Get started on the subject that Professor Ahern calls “the science of us”— biochemistry and its allied field molecular biology, which both tell us who we are. Discover the handful of elements involved in biochemical reactions; the bonds they form; and the wide array of molecules that result, including amino acids, which are the building blocks of proteins. Also, learn about the major types of living cells.

 Investigate why water is so singularly suited to life. Composed of two hydrogen atoms for each oxygen atom, water molecules have a polar charge due to the uneven arrangement of shared electrons. See how this simple feature allows water to dissolve sugars and salts, while leaving oils and fats untouched. Also learn what makes water solutions acidic or basic, and how this property is measured on the pH scale.

 Take a tour through the 20 amino acids that link together in different combinations and sequences to build proteins. Besides water, proteins are the most abundant molecules in all known forms of life. Also the most diverse class of biological molecules, proteins make up everything from enzymes and hormones to antibodies and muscle cells—all based on an alphabet of 20 basic building blocks.

 Learn how peptide bonds join amino acids to form an almost unlimited number of protein types. The order of amino acids matters, but even more important are the shapes they form. Survey primary, secondary, tertiary, and quaternary protein structures, with examples—from silk (a fibrous protein with mostly secondary structure) to the intricately folded hemoglobin protein (a quaternary structure).

 Discover how proteins fold into complex shapes, often with the help of molecular chaperones. Then learn the deadly consequences of proteins that do not fold properly, leading to degenerative conditions such as Alzheimer's, Parkinson's, and prion diseases. Also look at intrinsically disordered proteins, which lack a fixed structure, permitting flexible interactions with other biomolecules.

 Hemoglobin is the protein in red blood cells that carries oxygen from lungs to tissues and then takes away carbon dioxide for exhalation. Learn how structure is the key to this complicated and vital function. Also see how variant forms of hemoglobin, such as fetal hemoglobin and the mutation behind sickle cell anemia, can have life-saving or fatal consequences—all depending on structure.

 Witness how structure and function are related in enzymes, which are a group of proteins that stimulate biochemical reactions to run at astonishing speed. One example is OMP decarboxylase, an enzyme that produces a crucial component of DNA in a blistering 0.02 second, versus the 78 million years that the reaction would normally take! Analyze the mechanisms behind these apparent superpowers.

 How do cells control the tremendous power of enzymes? Study the ways that cells regulate enzyme activity by directing the synthesis and breakdown of biomolecules. One reason biochemists care so much about enzymes is that many medical conditions result from enzyme activity that is excessive or insufficient. Consider examples such as hemophilia, hypertension, and high cholesterol.

 Lipids are a varied group of molecules that include fats, oils, waxes, steroids, hormones, and some vitamins. Survey the fats that obsess us in our diets and body shapes, notably triglycerides in their saturated and unsaturated forms. Then explore the role lipids play in energy storage and cell membrane structure, and cover the multitude of health benefits of the lipid vitamins: A, D, E, and K.

 Probe the biochemistry of sugars that provide us with instant energy, feed our brains, direct proteins to their destinations, and communicate the identity of our cells. On the other hand, when present in large quantities they can lead to Type 2 diabetes, and the wrong sugar markers on transfused blood cells can even kill us.

 Adenosine triphosphate (ATP) is the fuel that powers many processes in living cells. Every day we make and break down our own body weight in ATP. Focus on the chemical reactions behind this impressive energy conversion system, which is governed by the Gibbs free energy equation. These reactions, which can proceed either forward or backward, are among the most important in biochemistry.

 A metabolic pathway is a series of biochemical reactions, where the product of one serves as the substrate for the next. Biochemists compare these pathways to road maps that show the network of reactions leading from one chemical to the next. Follow the metabolic pathway called glycolysis that breaks up glucose and other sugars. Then trace the route for fatty acid oxidation.

 The products from the reactions in the previous lecture now enter the Krebs citric acid cycle. The outcome of these reactions, in turn, link to many other pathways, with the Krebs cycle serving as the hub directing the intricate traffic of metabolic intermediates. After decoding the Krebs cycle, use it to illuminate a deep mystery about cancer cells, which suggests new therapies for the disease.

 Thus far, your investigations have accounted for only part of the energy available from food. So where's all the ATP? In this lecture, see how ATP is produced in abundance in both animal and plant cells, largely via mitochondria (in animals and plants) and chloroplasts (in plants only). You also learn why we need oxygen to stay alive and how poisons such as cyanide do their deadly work.

 Take a tour of cell manufacturing, focusing on metabolic pathways that use energy to synthesize key molecules, including sugars, complex carbohydrates, fatty acids, and other lipids. Along the way, learn why alcohol and exercise don't mix, how our bodies create short- and long-term energy stores, and why some essential fatty acids can lead to health problems if their ratios are not optimal.

 The word “cholesterol” evokes fear in anyone worried about coronary artery disease. But what is this ubiquitous lipid and how harmful is it? Examine the key steps in cholesterol synthesis, learn about its important role in membranes, and discover where LDLs (“bad” cholesterol) and HDLs (“good”) come from. It isn’t cholesterol alone that is plugging arteries in atherosclerosis.

 See how cells manage complex and interconnected metabolic pathways, especially in response to exercise and a sedentary lifestyle. Then discover the secret of warm-blooded animals and what newborn babies have in common with hibernating grizzly bears—with lessons for combatting obesity. Also, learn about a drug from the 1930s that helped people burn fat in their sleep—as it killed them.

 Study how plants use sunlight and reduction reactions to build carbohydrates from carbon dioxide and water. This synthesis of food from air and water occurs in a series of reactions called the Calvin cycle. While humans exploit plants for food and fiber, we also utilize a multitude of other plant molecules called secondary metabolites. These include flavors, dyes, caffeine, and even catnip.

 Nitrogen is a key component of amino acids, DNA, and RNA, yet animal and plant cells are unable to extract free nitrogen from air. See how bacteria come to the rescue. Then follow the flow of nitrogen from bacteria to plants to us. Also look at strategies for reducing our reliance on environmentally unsound nitrogen fertilizers by exploiting the secret of 16-feet-tall corn plants found in Mexico.

 Discover how to eat in a way that minimizes harm and efficiently fixes the inevitable damage from living. Learn that certain cooking methods can increase the formation of harmful compounds. And substances such as antioxidants found in some foods can reduce the impact of damaging chemical reactions within cells. Also cover recent findings about gut bacteria that have changed our views about diet.

 Cellular communication depends on specific molecular interactions, where the message and the receiver are biomolecules. Follow this process for signaling molecules such as the hormones epinephrine, adrenalin, and epidermal growth factor, which stimulates cells to divide. Cellular signaling is like the children's game called telephone, except the message is usually conveyed accurately!

 When you touch a hot stove, you recoil instantly. How do nerve cells process information so quickly? Trace nerve impulses—which involve electrical signals and neurotransmitters—as they pass from neuron to neuron, and from neuron to muscle cells. Study molecules that block nerve transmissions, such as snake venom and Botox treatments, and look at the role of dopamine in addiction behaviors.

 Most of the reactions you have studied so far occur outside everyday awareness. Now investigate the most important biochemical signals that we habitually notice: the molecular reactions that give rise to the five senses. Analyze the sensory origins of colors, sounds, tastes, smells, and touch, mapping them through the nervous system. Observe how the senses are “tuned” to enhance our survival.

 Trace the pathways of two widely ingested molecules: caffeine and fructose. Caffeine fools the body—usually harmlessly—into increasing glucose in the blood, while too much fructose can lead to unhealthy accumulation of fat in the liver. Then focus on two topics that link with the upcoming molecular biology segment of the course: androgen insensitivity and the molecular mechanisms of aging.

 Advance into the last third of the course, where you cover molecular biology, which deals with the biochemistry of reproduction. Zero in on DNA and how its double-helix structure relates to its function. Then look at the single-stranded RNA molecule, which is a central link in the process, “DNA makes RNA makes protein.” Also consider how viruses flourish with very little DNA or RNA.

 Focus on DNA's ability to replicate by matching complementary base pairs to separated strands of the helix. Several specialized enzymes are involved, as well as temporary segments of RNA. Explore this process in bacteria. Then investigate the polymerase chain reaction (PCR), a Nobel Prize-winning technique for copying DNA segments in the lab, which has sparked a biotechnology revolution.

 Examine the cell cycle of eukaryotic cells like our own and the cycle's effect on DNA replication. Discover that a quirk in the copying of linear DNA leads to shrinking of chromosomes as cells age, a problem reversed in egg and sperm cells by the telomerase enzyme. For this reason, telomerase might appear to be the secret to immortality except its unregulated presence in cells can lead to cancer.

 Cells go to great lengths to prevent mutations. Luckily, these measures are not quite perfect, since nature relies on mutations to drive evolution. Study the methods that cells use to minimize alterations to their DNA. Find that DNA repair can interfere with cancer treatment, when the malignant cells survive medical therapy by repairing their DNA faster than the treatment can halt the repair.

 Delve deeper into DNA replication, learning that a process called genetic recombination assures that no two individuals will have the same DNA, unless they are twins derived from a single fertilized egg. Trace the new technologies that have arisen from our understanding of recombination and repair of DNA, notably CRISPR, which permits precise alteration of gene sequences.

 RNA is more than simply a copy of the DNA blueprint. Focus on the synthesis of RNA, covering how it differs from DNA replication. Also learn how human cells shuffle their genetic code to make about 100,000 different proteins using fewer than 30,000 coding sequences. Finally, see how knowledge of transcription occurring after death helps forensic scientists establish the time of death accurately.

 Learn how cells solve the problem of reading information in messenger RNA and using it to direct protein synthesis. Focus on how different parts of the translation apparatus work together through sequence-specific interactions. Also discover how antibiotics kill bacteria and what makes the bioterrorism agent ricin so deadly. Close by investigating techniques to create biological drugs on demand.

 Explore the controls that determine which genes are expressed at a given time, where in the body, and to what extent. Controls that act over and above the information in DNA are called epigenetic, and they can be passed on to offspring for a generation or two. Consider the case of honeybees, where a special food affects which genes are expressed, turning an ordinary larva into a queen bee.

 Roughly 10,000 human diseases may be caused by mutations in single genes. Review the nature of genetic disorders, such as cystic fibrosis, hemophilia, and Alzheimer’s. Also examine diseases that emerge from mutations in mitochondrial DNA. Finally, assess the challenges of using gene therapy and other technologies to treat genetic diseases—issues that raise technical, legal, and ethical problems.

 Cover the ways that cells become cancerous, notably through a series of unfortunate mutations that lead to uncontrolled cell division. Genetics, environmental factors, infections, and lifestyle can also play a role. Learn why elephants don't get cancer. Then look at approaches to treating cancer, including use of agents that target rapidly dividing cells, whose side effects include hair loss.

 Molecular biology allows scientists and engineers to manipulate the recipes written in our genes. Spotlight some of the developments drawing on these techniques, including cloning, reprogramming cells, harnessing stem cells, and initiatives in “synthetic” biology, a new field that lets researchers create genomes that have never before existed, essentially fashioning entirely new life forms.

 Close by surveying exciting developments in molecular biology that are now unfolding. One area has been dubbed “omics,” based on the explosion of applications due to genomics, which is the decoding of human and other genomes. Thus, we now have “proteomics,” “transcriptomics,” and other subfields, all exploiting our knowledge of the DNA sequences responsible for specific biochemical pathways.