9-23-2010 A&P Lecture

Endocrine system next week Labs will compliment the lectures Chapters 1,2 & 3, but you MUST READ CHAPTER 4 (tissues) Read over material in text prior to lectures, as the more you see the material, the better off youll be. BIOMOLECULES (See Table 2.1) Common elements are (C,O, H and N) Comprise approximately 96% of our body mass

Sodium is the element in the highest concentration in extracellular fluid o Kidneys work hard to maintain concentration in your circulation

Potassium is the most abundant cation in the intracellular fluid All proteins contain sulfur Chloride is an anion plentiful in extracellular fluid If one has low iron levels, they may have difficulty breathing o Hemoglobin has an iron moidy(?) that binds oxygen

MACROMOLECULES Carbohydrates, lipids, nucleic acids and proteins Made up primarily of the above elements Macromolecules in large part are polymers of many monomers (subunits) Carbohydrates Monosaccharides are monomers of carbohydrates o These come in many forms with general formula Cn(H2O)n where n can be any number o Most common are those in which n is equal to 5 or 6 (number of carbons)

Some carbon ones are shown in Figure 2.14 (pg. 45) which depicts a number of monosaccharides Pentose (5 C) Deoxyribose (5 C) Ribose (5 C) from DNA and RNA Glucose (6 C) Fructose (6 C) Galactose (6 C) Glucose is very important as it is the monosaccharide transported into cells and used for energy production. It is the reason we have insulin (to stimulate the transport of insulin into your various cell types)

Polysaccharides are chains of monosaccharides (one or more monosaccharides linked together) o Disaccharides (two sugars) o Linked via dehydration synthesis (e.g. glucose combined with fructose with the liberation of water, forming the disaccharide sucrose or table sugar) See Figure 2.15 (pg. 45) Sucrose must be converted back to glucose and fructose after drinking your iced tea in order to absorb the monosaccharides (hydrolysis reaction) Accomplished by an enzyme called sucrase o Will be important when studying GI tract Lactose and Maltose are important disaccharides (maltose in malts, and lactose in breast milk) Lactose is a disaccharide of galactose and glucose Must also be hydrolyzed to be absorbed o Ultimate polymer: Glycogen (a polysaccharide with lots of glucose molecules that is a storage form ) Found in ones liver and muscles (primary storage locations) See Figure 2.16 (pg. 46) Sucrose broken down after eating, and you absorb the glucose if it isnt needed for energy as glycogen When youre running, glucagon causes the breakdown of glycogen, and the release of glucose which then becomes available for energy production Glycogen is a storage form for carbohydrates

Lipids Composed predominantly of carbon and hydrogen, sprinkled with a little oxygen Fatty Acids are common building blocks of lipids (the monomers)

Only very small fatty acids are present in circulation, but larger ones like palmitic acid (15 C) are highly hydrophobic (i.e. dont like being in aqueous solution) o Most of the lipid in circulation are found in glycolipids (HDLs and LDLs) Checked and evaluated when having your cholesterol checked High-Density Lipoproteins & Low-Density Lipoproteins LDLs are the bad ones and HDLs are the good ones o Fatty acids can be saturated (long carbon chains joined by single bonds) Present in high conc in animal fats Dont want to have lots of this in your diet o Can be unsaturated (like oleic acid which is a mono-unsaturated fatty acid) Present in vegetable fats Not as bad as saturated Triglycerides are the main form of fat in the human body o Where fatty acids are joined to a carbohydrate known as glycerol 3 fatty acids can be found on glycerol (hence tri-) Humans capacity to store triglycerides is almost limitless o The fatty acids here can be any number of them See Figure 2.17 (pg. 47) o This is the storage form for a lot of lipids in the body o Major energy source which provides more than 2-fold as much energy as is liberated from the metabolism of a lipid compared to a protein or carbohydrate o REMEMBER: fatty acids can be in triglycerides, but also in other types of lipids such as phospholipids (very important components of cell-membranes), and can also be modified for very specific functions such as hormones! Phospholipids are a class of lipids that are a main component of all cell membranes (can form lipid bilayers) o most contain glycerol, a phosphate group and a simple organic molecule such as choline (nitrogen-containing substance, phosphatidylcholine here) (see Figure 2.18 pg. 49) with two fatty acids (one of which can be arachidonic acid) If arachidonic acid is there and so is phospholipase A2, it will chop it off, making it available for production of prosts and leuks The bubble at the top is comprised of the phosphate group, above which can be found choline Below this polar head are the nonpolar tails comprised of stearic acid on the left, and palmitic acid on the right. This molecule is termed amphipathic as it has both polar and nonpolar ends/regions o If you take some phosphatidylcholine and you swish it around in water, youll end up with numerous micells Membrane-bound hollow spheres Spontaneously form Non-polar tails face each other and polar head portions face the outside

This characteristic of phospholipids has been used to make drug-carriers termed liposomes If you add the drug to the aqueous solution, then add the phosphatidyl serene etc., your drug will be placed inside the center of the spheres Then place something on the outside of the micells that will allow them to target a specific area (tumor or cell etc.) Drug will then be delivered to that specific site, and because of said targeting, and due to nature of the lipid membrane, it will actually dissolve into the plasma membrane of the cell, allowing effective delivery of the drug! o Difficult area of research is the targeting process

Eicosanoids (special type of lipid) Eicosanoids are specialized types of fatty acids that are modified and mediate all kinds of effects 2 classes: Prostaglandins & Leukotrienes (many of both) These come from a precursor fatty acid known as arachiconid acid (20 C) o Present in a number of phospholipids that are present in the cell membrane o You have a phospholipid with fatty acids down to it, one of which is arachidonic acid. How does arachidonic acid become available to make prostaglandins etc.? There is an enzyme that cleaves arachidonic acid from the phospholipid known as phospholipase A2 In the presence of this enzyme, arachidonic acid is liberated. It can then be converted to one of a number of prostaglandins or a leukotriene What enzyme converts arachidonic acid to prostaglandins?? Cyclooxygenase o 2 forms: COX-1 and COX-2 Cyclooxygenase-1 & 2 What enzyme converts arachidonic acid to leukotrienes?? Lipoxygenase These two eicosanoids have different jobs, one of which is the regulation of circulation, uterine contractions, blood clotting etc., but very importantly, the INFLAMMATORY RESPONSE o Symptoms of Inflammation Swelling Redness Heat Pain Loss of Function

NSAIDS (non-steroidal anti-inflammatory drugs) are taken for inflammation, a symptom of arthritis (chronic and severe inflammation) etc. The gold-standard NSAID is aspirin (acetylsalicylic acid) There are other better drugs, but aspirin is the standard Works by blocking cyclooxygenase (irreversibly!) It is a suicide-substrate for it! It acetylates cyclooxygenase. If cyclooxygenase is knocked out, prostaglandins arent produced, so process of inflammation is suppressed. Ibuprofen, Piroxecam etc. Viox was a COX-2 inhibitor Aspirin is mostly a COX-1 inhibitor

WARNING: THERE IS NO SUCH THING AS A SELECTIVE INHIBITOR!!!! So, while aspirin is a COX-1 inhibitor (primarily), it is also slightly inhibits COX-2. There is no selective drug. Beta-1 antagonists for treatment of hypertension are also beta-2 inhibitors, but they dont tell you that.

Leukotrienes arent taken care of with aspirin though, so its not entirely the best Glucocorticoids are great anti-inflammatories, as they zap both prostaglandins and leukotrienes LOTS of side-effects though if taken cronicaly Organ-transplant patients took glucocorticoids as theyre immunesuppressives, but they have lots of side-effects, so early on, all organ-recipients would develop a cushionoid appearance (round face etc.) They are great anti-inflammatory drugs though, as they inhibit phospholipase A2, thereby inhibiting the generation of both prost and leuks! Cardiovascular effect of aspirin is the inhibition of platelet-aggregation, so it prevents clotting. You dont want a bit clot in the coronary artery. Its because it blocks cyclooxygenase

Steroids (another type of lipid) All andogenous steroids are produced from cholesterol One of the reasons you need cholesterol (and why your liver makes 85% of the cholesterol you need) is that its the precursor for all steroids! See Figure 2.19 4 interconnected carbon rings

Rings are modified by side groups See aforementioned figure Cortisol is a glucocorticoid (made in the adrenal cortex) Aldosterone (also made in the adrenal cortex) Very important to salt and water balance

Proteins Polymers of amino acids All amino acids have the structure shown (See Figure 2.20 pg. 51) o Differ from each other by the side chain or R-Group Amino group and carboxylic acid can either be charged or uncharged o pKa of side groups can calculate under what condition they can be ionized etc. If amino acid is VERY simple and has just a proton, thats Glycine (simplest) 20 amino acids or so Can contain sulfur as in methionine and cysteine Can be aromatic as in tyrosine Can be basic as in lysine Combine with each together via peptide bonds to make proteins o Dehydration reaction where water is liberated forming a dipeptide (two amino acids) o See Figure 2.21 pg. 51 o Enzymes called proteases can break these strong bonds Proteins vary in size and length o Can be quite simple (e.g. 3 amino acids, thyrotropin-releasing hormone or TRH produced in hypothalamus which regulates thyroid gland) o Can be quite large (e.g. 200 amino acids in human growth hormone!) GH o PRLR (prolactin receptor contains greater than 500 amino acids! LEVELS OF PROTEIN ORGANIZATION o Multiple levels of organization (See. Figure 2.22 pg. 52) Primary Order/sequence of amino acids (e.g. glycine-arginine-phenylalanine) Secondary Interaction of amino acids in a particular protein with each other! o Due to charged nature of amino group and carb acid groups as well as R group interaction o Can form beta-pleated-sheets and alpha-helices Tertiary 3-dimensional arrangement such as in a globular protein is its tertiary structure Quaternary Two proteins interacting with each other

E.g. FSH, LH, ACPH and Insulin receptors o All have 2 protein subunits which are in themselves polypeptide units o So if we have 2 proteins interacting in some way to form a complex, thats the quaternary structure

Enzymes (a type of protein) Most enzymes are proteins Enzymes catalyze chemical reactions, or rather, facilitate them E.g. Sucrase o Brush Border Enzyme, meaning it exists in the brush border of your intestinal mucosa o If you drink iced tea with sugar in it, you cant absorb that sucrose, but it runs into sucrase in small intestine, and glucose and fructose can then both be absorbed Enzymes are VERY specific for their substrates (Lock and Key mechanism) Interaction occurs without any change to the enzyme Enzyme free to act with another molecule of sucrose etc once reaction complete

FUNCTIONS OF PROTEINS Transport (as in carrying O2) Structural (as in the cytoskeleton) Facilitation of Reactions (as in enzymes) Regulatory Functions (as in Adenalate Cyclase) Immunological Functions (as in when youre immunized or contract an infection) o Production of antibodies

REMEMBER: Proteins make up about 50% of organic components of an individual