Cell Chemistry

Those special proteins we call Enzymes The myriad of chemical reactions occurring in the cell are collectively called metabolism. Metabolism can be divided into two categories: 1) catabolism, the breakdown of molecules, and 2) anabolism, the synthesis of new molecules. We will look at two aspects of metabolism: 1) enzymes, and 2) energy and metabolism. (We will cover some aspects of the last section of chapter 3, biosynthesis, later.) Enzymes: Enzymes are protein catalysts. (Note: there are also catalytic RNAs.) A catalyst increases the rate of a chemical reaction without itself being permanently changed. Enzymes bind (lock and key binding) to a substrate (or substrates). After the reaction, an end product (or end products) is (are) released. While the enzyme may have been altered in the intermediate substrate-bound stage, it is released unaltered and can be reused. Therefore, a small amount of enzyme can catalyze numerous reactions.	Lock-and-Key Model Induced Fit Model Enzymes are things invented by biologists that explain things which otherwise require harder thinking. -- Jerome Lettvin
Enzyme Catalysis: Enzymes increase reaction rates by lowering the activation energy needed for a reaction to occur, often by bringing two substrates into proximity and into the right configuration. Enzyme-substrate binding according to the lock-and-key model involves various noncovalent interations (hydrogen bonds, ionic bonds, hydrophobic interactions). Also, the binding itself may be altered by the substrate binding inducing it to take on a different shape and altering the enzyme's activity (induced fit model). Enzymes have a binding/catalytic site. At the catalytic site, amino acids of the enzyme may actively participate in the chemical reaction even becoming covalently linked to the substrate in its intermediate form. Substrate-Enzyme Binding Chymotrypsin	Lowering the Activation Energy
Coenzymes: A coenzyme is a type of prosthetic group (small, non-protein molecules bound to proteins, like heme). Coenzymes are small organic molecules that further increase reaction rates. One example is the nucleotide called nicotinamide adenine dinucleotide (NAD⁺) which can be reduced (to NADH) by receiving one H+ and two electrons and then oxidized (back to NAD⁺) by donating these to another molecule. The reduction/oxidation of NAD+/NADH is coupled to the oxidation/reduction of other molecules. NAD⁺ ---> NADH requires energy. NADH ---> NAD⁺ releases energy. (Video) Similarly, the nucleotide called flavine adenine dinucleotide (FAD) can be reduced to FADH₂ (requiring energy) and FADH₂ can be oxidized to FAD (releasing energy).
Enzyme Inhibition/Activation: Enzymes are often inactivated by the presence of a pathway end product that binds to a site other than the catalytic site (allosteric binding). This is feedback inhibition. (F.E. Video.) Enzymes may also be activated or deactivated by the addition of phosphate groups to a serine, theonine, or tyrosine amino acid side chain. This is phosphorylation. The activity of enzymes responsible for phosphorylation (a protein kinase) may in turn be regulated by phosphorylation (another protein kinase). (Video at 5:50) Enzymes that remove phosphates are called protein phosphatases.	Allosteric Binding Feedback Inhibition

Membranes Membranes are found throughout eukaryotic cells and all have the same basic chemical structure. The main component of membranes is the phospolipids, but there are also other lipids as well as proteins and carbohydrates found in membranes. Phospholipid Bilayer: The phospholipid bilayer is the basic structure of all cellular membranes. Fluid Nature of Phospholipid Bilayer	Cell Membrane
Phospholipid Molecules: These amphipathic molecules will self-assemble into a bilayer in an aqueous solution. Other Amphipathic Molecules: Cholesterol and other amphipathic molecules are also in the bilayer. The presence of these, as well as the types and lengths of the fatty acids, determine the membrane's fluidity. Fluid Mosaic Model of the Membrane: The cell membrane is actually a fluid. Phospholipids and proteins in the membrane can move around and rotate.
Proteins: Membrane proteins may be anchored in the phospholipid bilayer of attached to the outer surface of the membrane. Membrane Proteins: These may be integral membrane proteins or peripheral membrane proteins (associated with other membrane proteins).	Membrane Proteins
Integral Membrane Proteins: These are an integral part of the membrane (duh!). Transmembrane Proteins: These proteins pass through the membrane. Single Pass vs. Multiple Pass Proteins: Some integral membrane proteins pass through the membrane only once (an alpha helix crosses the membrane), while others double back and pass more than once (more than one alpha helix). Lipid Linked Proteins: Some proteins are covalently linked to the heads of membrane phospholipids. Peripheral Proteins: Some proteins are attached to other membrane proteins. They may attach to then dissociate from the membrane (not a permanent part of the membrane)(G-protein, which we will cover in "Cell Signalling," is a peripheral protein.) Membrane Carbohydrates: Membrane carbohydrates may be attached to exterior membrane proteins or phospholipid heads. (Can you see the difference between the internal or cytosolic side and the external or noncytosolic side?) All of these carbohydrates together form the glycocalyx important in cell recognition. Transport across Membranes: Passive Diffusion: Small uncharged molecules, some medium-small uncharged molecules, and small polar molecules can diffuse across (through) the phospholipid bilayer. Facilitated Diffusion, Channel Proteins, and Carrier Proteins: Some ions and charged molecules diffuse into or out of the cell with the aid of special membrane proteins such as channel proteins (open and close) or carrier proteins. (A channel protein and high blood pressure) Carrier Proteins, Active Transport, and ATP: Carrier proteins may also be involved in the ATP-dependent process of active transport across the membrane (independent of concentration). Macromolecules: Very large molecules must enter by endocytosis (pinocytosis and phagocytosis). We will look at these processes later.	Beta Barrel Facilitated Diffusion Active Transport

Thought of the Day: Do illiterate people get the full effect of Alphabet Soup?

Molecules The molecules of the cell are classified as inorganic compounds (relatively small with little or no carbon) or organic compounds (larger molecules rich in carbon). Inorganic: Water: Water is the most abundant molecule in cells (~70% in the average cell). It is a polar molecule and the intermolecular hydrogen bonds are responsible for many of its properties. It is an excellent solvent. Other: Numerous other inorganic, such as various ions, dissolved gases, and others, are important in many cellular mechanisms.
Organic: Carbohydrates: These molecules have abundant chemical potential energy. They are called carbohydrates because the atoms C:H:O are approximately in a 1:2:1 ratio (carbo = C; hydrate = water). Sugars: Sugars are smaller carbohydrates and may be linear or ring shaped. Monosaccharides (Simple Sugars): These are 3-7 carbons carbohydrates. Often they have 5 or 6 carbons. Disaccharides: A glycosidic bond joins two monosaccharides. (alpha (1-4))

Polysaccharides/Oligosaccharides: These carbohydrates are composed of 100s to 1000s of monosaccharides. Starch (contrary to what this movie says, starch is not in animals): This class of carbohydrates is found in plants; amylopectin is an example and has some alpha (1-6) bonds making it a branched molecule. Glycogen: This is a large carbohydrate found in animals. (Sometimes called "animal starch.") Also branched. Cellulose: This carbohydrate is present in plant cell walls and has beta (1-4) bonds (we cannot digest them). (Dietary fiber and colon cancer.)(Dietary fiber and diabetes)
Glycoproteins/Glycolipids: carbohydrate-protein, carbohydrate-lipids)
Lipids: These are also energy molecules, some involved in cell signalling. Fatty Acids: These are hydrocarbon(Fatty acids may be as short as 4 Cs, or as long as 28 Cs and most naturally-occurring fatty acids have an even number of Cs, according to that infallible site, Wikipedia. Many have 16 or 18 Cs or somewhere in the low 20s.) Saturated Fatty Acids: Saturated fatty acids have no double bonds between the carbon atoms (saturated with hydrogens). Unsaturated Fatty Acids: These have at least one double bond. Monounsaturated Fatty Acids: These have exactly one double bond. Polyunsaturated Fatty Acids: These have more than one double bond and are good for cardiovascular health.
Trans Fats versus Cis Fats: Recent discoveries have shown that the configuration around the double bond is extremely important: trans = bad and cis = good for cardiovascular health. (Trans fats and heart disease)(Ranking of fatty acids according to heart health)
Triacylglycerols (triglycerides, fats): These lipids are composed of a glycerol plus 3 fatty acids. Glycerol: A 3 carbon molecule with 3 hydroxyls. Fatty Acids: A hydroxyl of glycerol reacts (synthesis reaction) with the hydroxyl of the carboxyl group of the fatty acid forming an ester bond.
Phospholipids: These are common membrane lipids and are amphipathic. Phospholipid: This is a glycerol + 2 fatty acids + another phosphate-containing small molecule. Sphingomyelin: This is similar to phospholipids but has serine + 2 fatty acids.
Glycolipids: These are also amphipathic made up of a carbohydrate + another molecule + 2 fatty acids.
Steroids: These molecules have hydrocarbon rings (4) with a hydroxyl and also are amphipathic. Cholesterol: A common membrane steroid. Steroid Hormones: Many (but not all) hormones are steroids, including cortisol and testosterone.
Nucleic Acids (and Related Molecules): These are polynucleotides. There are two types: DNA and RNA. A nucleotide is composed of a phosphate, a pentose sugar, and a nitrogen base. Nucleotides: These are the building blocks of polynucleotides but they also include other molecules important molecules like ATP and cAMP. Phosphate: PO₄ Pentose: The pentose of RNA is ribose and the pentose of DNA is deoxyribose (2'-deoxyribose). Nitrogen Base (Base): Nitrogen bases are ring-molecules and come in two basic shapes: purines and pyrimidines. Purines: Purines are double-ring molecules. Adenine, Guanine: These are the two types of purine and are found in both DNA and RNA. Pyrimidines: These are single ring molecules. Cytosine, Thymine, Uracil: Cytosine is found in DNA and RNA; thymine is found only in DNA; uracil is found only in RNA.
Base Pairing: Hydrogen bonds: A-T (or A-U) and G-C pairs base pairs form between the bases of polynucleotides. Nucleosides versus Nucleotides: A nucleoside is a sugar-base. A nucleotide is a sugar-base-phosphate (may have more than one phosphate).
Polynucleotides: DNA and RNA: DNA and RNA have polarity; they have 5' and 3' ends.
Proteins: Proteins are polypeptides and have numerous functions including structure, defense, and enzymes. Amino Acids: There are 20 kinds of amino acids. Each has an amino end and a carboxyl end with a unique radical. The radical gives the amino acid it characteristics:
Non-Polar Amino Acids: Some radicals are neutral. Polar Amino Acids: Some radicals are polar. Basic Amino Acids: Some radicals are basic (+ charge). Acidic Amino Acids: Some radicals are acidic (- charge).
Peptide Bond: The carboxyl end of one amino acid forms a covalent bond with the amino end of another amino acid (synthesis reaction): the C-N peptide bond. Protein Structure: Proteins have three or four "degrees of structure." Primary Structure: This is the amino acid sequence and is all important.
Secondary Structure: This is the local amino acid interactions that give 3D structure. Alpha-Helix: Hydrogen bonds form between amino acids holding it in a right-handed helix and neutralizing the polarity of the carboxyl and amino groups. (Hydrophobic)(Pauling video) Beta-Sheet: Also held together by hydrogen bonds. (Hydrophobic)
Tertiary Structure: Various non-local amino acid interactions determine other 3D structures. Proteins have structurally and functionally related regions called domains.

Quaternary Structure: Some proteins are made up of more than one polypeptide (dimer, trimer, tetramer, ... ) Cysteine-related disulfide bridges may hold two polypeptides together in extracellular proteins.
	Disulfide Bridges