Biochemistry Unit 3 Notes

[Cameron Fluet]

Themajor in Chemistry: Biochemistry is designed to meet the educational and research needs of students with an emphasis on the biochemical sciences and biological chemistry/chemical biology. As with the Chemistry major, an emphasis on research skill development builds on a core of courses covering the principal areas of chemistry as an intellectual foundation for biochemistry. Research in biochemistry is also strongly supported within this major. Chemistry: Biochemistry majors are exceptionally well prepared for graduate education and careers in chemical research, teaching, the biochemical industry, or regulatory agencies; as a premedical track, the major provides excellent preparation for professional training in medicine and related health fields.

All students should refer to the Departmental Regulations section of the Chemistry Department page for important stipulations. NOTE: Students may not switch tracks in general or organic chemistry after the initial course in the sequence.

The Chemistry: Biochemistry major requires a minimum of twelve 4-unit courses in chemistry, as well as two biology, three math, and two physics 4-unit courses. Unless noted otherwise, all required courses are 4 unit hours. All required chemistry courses must be completed with a grade of C or higher.

Minimum 16 hours per week of experimental or theoretical research within a chemistry department, or approved research group outside the chemistry department undertaking research in the chemical sciences. An Honors thesis will be submitted at the end of the spring term and defended before a committee of three faculty members. A grade of B or higher is required in CH 401 and CH 402 in order to graduate with Honors in Chemistry. An oral presentation at the Undergraduate Research Symposium at the end of the spring term is also required.

You have probably studied the cell many times, either in high school, or in college biology classes. There are many websites available that review both prokaryotic (bacterial and archeal cell types) and eukaryotic cells (protist, fungi, plant, and animal cell types). All cells have some similar structural components, including genetic material in the form of chromosomes, a membrane bound lipid bilayer that separates the inside of the cell from the outside of the cell, and ribosomes that are responsible for protein synthesis. This tutorial is designed specifically from the viewpoint of chemistry. It explores four classes of biomolecules that are also present in all cell types (lipids, proteins, nucleic acids and carbohydrates) and describes in a simplified pictorial manner where they are found, made, and degraded in a typical eukaryotic, animal cell (i.e. their history). This cell review focuses on the organelle structures common in eukaryotic cells. Subsequent chapters will concentrate on the structure and function of specific biomolecules.

The building and breaking down of life-sustaining chemicals within an organism is known as Metabolism. Overall, the three main purposes of metabolism are: (1) the conversion of food to energy to run cellular processes; (2) the conversion of food/fuel to building blocks for the production of primary metabolites, such as proteins, lipids, nucleic acids, and other secondary metabolites; and (3) the elimination of waste products. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments.

Figure 1.1 Catabolic and Anabolic Reactions. Catabolic reactions involve the breakdown of molecules into smaller components, whereas anabolic reactions build larger molecules from smaller molecules. Catabolic reactions usually release energy whereas anabolic processes usually require energy.

Figure 1.2 Mechanisms of Enzyme-Substrate Binding. (A) In the Lock and Key Model, substrates fit into the active site of the enzyme with no further modifications to the enzyme shape required. (B) In the Induced Fit Model, substrate interaction with the enzyme causes the shape of the enzyme to change to better fit the substrate and mediate the chemical reaction.

Metabolism is a feature of all cellular life, from the very simplistic prokaryotic cells (Archae and Bacterial cells) to the more complex eukaryotic cells (Fungi, Animal and Plant cells) (Fig. 1.3). Prokaryotic cells and eukaryotic cells are defined by major differences in size and structural features. Prokaryotic cells are simplistic cells that are approximately 1,000 times smaller than their eukaryotic counterparts. All prokaryotes have a single, circular chromosome located in a nucleoid region of the cell, as well as ribosomes that produce proteins that perform cellular metabolic functions. Prokaryotic cells also contain a plasma membrane and external cell wall structure. Some prokaryotes also have cilia or flagella that aid in locomotion.

Figure 1.3 Structure of Prokaryotic and Eukaryotic Cell Types. Depiction of the relative size of a prokaryotic cell (A) which is approximately 1,000 times smaller that a eukaryotic cell (B). All prokaryotic cells contain a chromosomal DNA that is concentrated in a nucleoid, ribosomes, and a cell membrane-cell wall system. Some prokaryotic cells may also possess flagella, pili, fimbriae, and capsules. Eukaryotic cells are much larger than procaryotic cells and require the additional compartmentalization of structures into membrane-bound organelles to mediate metabolic functions.

The design for a cell mostly resides in the blueprint for the cell, the genetic code, which is comprised of deoxyribonucleic acid (DNA) housed in the cell nucleus and a small amount in the mitochondria (Figure 1.5). Of course, the DNA blueprint must be read out or transcribed into ribonucleic acid (RNA) and then translated to proteins by ribozome structures, which themselves were encoded by the DNA and contain a combination of RNA and protein subunits. The genetic code has the master plan that determines the sequence of all cellular proteins, which then perform almost all other activities in the cell, including enzymatic functions, motility, architectural structure, transport, etc. In contrast to DNA, RNA and protein polymers, the formation of the other two major macromolecules (carbohydrates and lipids) are not driven by such a template but rather by the enzymes that catalyzes the synthesis.

Figure 1.5 The Blueprint for Life is Housed in Deoxyribonucleic Acid (DNA). Within eukaryotic cells DNA is localized to two major places within the cell. The first is the nuclear DNA that forms linear chromosome structures (shown on the right). The second is the circular DNA housed in the mitochondria (shown on the left). The mitochonrdial structures replicate independently of the cell and are thought to have originated as prokaryotic symbionts during the early evolution of the eukaryotic cell type.

Many of the chemical constituents of the cell arise not from direct synthesis but from import of both small and large molecules. The imported molecules must pass through the nonpolar lipid bilayer that forms the cell membrane, and in some cases through additional membranes if they need to reside inside membrane-bound organelles. Molecules can move into the cell by two major processes, diffusionor active transport. The process of diffusion moves molecules down their concentration gradient from an area of high concentration to an area of low concentration and does not require an input of energy. Active transport, on the other hand, requires energy to move molecules against their concentration gradient from an area of low concentration to an area of high concentration. Diffusion across the plasma membrane can either be passive or facilitated. In passive diffusion, small, nonpolar molecules (such as CO2 and O2) move across the membrane directly across the membrane (Fig 1.6A). Larger and/or polar molecules move by facilitated diffusion, which requires a channel or carrier protein (Fig 1.6B). Computer simulations of the facilitated diffusion of lactose or water across the membrane are shown at the following links: Animation of lactose diffusion through the LacY protein and Animation of water diffusion through the aquaporin channel, (These animations were created by the Theoretical and Computational Biophysics group at the Beckman Institute, University of Illinois at Urbana-Champaign. These molecular dynamic simulations were made with VMD/NAMD/BioCoRE/JMV/other software support developed by the Group with NIH support.)

Ion channels are specialized channels that allow the flow of ions across membranes. Some are permanently open (nongated) while others open or close depending on the presence of ligands (ligand gated) that bind the protein channel, the physical bending of the protein within the local environment (mechanical gated), or a change in the voltage/charge state (voltage gated) of the local environment of the protein in the membrane. Flow of ions through the channel proceeds in a thermodynamically favored direction, which depends on their concentration and voltage gradients across the membrane.

Figure 1.6 The Process of Cellular Diffusion. The movement of small, nonpolar molecules across the plasma membrane and down their concentration gradient occurs by passive diffusion (shown in A). Protein channels or carriers are required for the movement of larger and/or polar molecules, such as water, across the plasma membrane (shown in B). Note that diffusion processes will proceed and equalize concentrations of a molecule until a dynamic equilibrium is reached.

Molecules can also move against a concentration gradient in a process called active transport. Active tranport requires an input of energy, often in the form of ATP hydrolysis (Fig. 1.7). When ATP is used as the energy source, this is known as primary active transport. The Na+/K+ ATPase pump is an important example of active transport and works to set up chemical gradients inside and outside of the cell. For the hydrolysis of one ATP molecule, three Na+ are pumped outside of the cell, while two K+ are pumped inside the cell. Proteins that move two molecules in opposite directions are also known as antiporters (Fig 1.7). Other active transport systems can use the energy of a chemical gradient to move other molecules in the same direction. This is known as secondary active transport. An example of a secondary active transporter is the Na+/glucose symporter, that uses the energy of Na+ moving down its concentration gradient to move glucose into the cell against its concentration gradient. Note that a symporter is a transporter that moves two molecules in the same direction across the plasma membrane (Fig. 1.8).

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