Princeton bio

Author's Introduction MCAT Biology in Context Admission to medical school is a nebulous challenge Every facet of our being is scrutinized, from temperament to intellect, personal history to professional goals Each credential in the portfolio is an objectifying representation of complex life events that have taken place over years The process is frustrating because this objectification seeks to encapsulate all elements of our being, save one, which is excluded at the crucial moment: will We must use all of our creative powers to analyze and integrate what we have done and who we are becoming with the ultimate goal of ripping off our skin and laying passive on the chopping block The task is at once noble and demeaning, intellectual and bestial In the few months of our lives when we compile the application, we are forced to dissect our past and present, prognosticate our future, and humbly present the case to physicians who will make a diagnosis and either accept us as students or cut us out like tumors The MCAT is your only opportunity to take action during these crucial months It is the only part of the application that you can control after having committed yourself to applying The Biology component of the test is so important because it is the closest approximation -ofmea1cal school lffi!fprffnary purpose of the MCAT is not to assess your potential as a physician, your memory, or your ethics, but rather your ability to perform in medical school Hence, both Physical Sciences and Biological Sciences questions are designed to assess your ability to integrate old and new information to solve problems like those faced by medical students Even the Physical Sciences section requires a minimum of equations and mathematics Problem solving in the Biological Sciences is the best practice for the MCAT and for medical school Another crucial reason to put your best effort into studying biology in preparation for the MCAT is that each and every insignificant factoid will become the cornerstone of a massive edifice of knowledge during the first two years of medical school-the "basic science" years This means you can't study too much for the Biology section of the MCAT, as long as you have plenty of time before the test Nature of MCAT Biology The majority of questions are based on a Passage This is text or graphics or both, presenting information from the various fields within the broad category of Biology The Passage is representative of a textbook or article a medical student might have to read and understand There are three types of questions Type one tests memory: you walk in the door of the test room with the answer in your head Type two tests your ability to process new information: you must get the answer straight from the Passage Type three tests your ability to combine what you know with the new information given in the Passage and solve a unique problem The ratio of question types is approximately 1:2:3, meaning there are twice as many type twos as type ones, and three times as many type threes That means only one out of six questions tests only straight-up factual knowledge What's in this Book All factual knowledge required for the MCAT is contained within these pages You will note that the organization of MCAT Biology follows the topic outline of the Biology section given in the AAMC's MCAT Student Manual It is not necessary to use any more-advanced text in preparation for the test A difficulty is that it's not possible to include exactly 100% of the information you need going into the test I had to undershoot or overshoot I overshot by about 15% The MCAT is a conceptual test, requiring little straight memorization, so you might say I should have undershot, rather than risk burdening you with unnecessary details If this were a traditional text, that would be a good argument But it's not Although this book contains a massive amount of factual information, its purpose is not to stuff you with details It is to make you think iii The book contains two things that will help you perform well on the MCAT It contains 115% of the factual information you'll need This is good because if you read carefully, you'll get all the type one questions right But more importantly, consider this: the content of the Passages is similar to the extra 15% For example, you don't need to memorize the differences between skeletal, cardiac, and smooth muscle for type one MCAT questions But what if I approached you the day before the test and offered you a copy of a Passage on this subject? You'll find that Passage in the MCAT Science Workbook The extra 15% is that Passage The second thing the book has to prepare you is "grillage." That means it puts you on the grill, by asking you questions on the material you're studying In other words, the approach is Socratic Some of the questions test factual knowledge that has already been presented Others ask you to speculate, based on new information Others force you to integrate factual knowledge and speculation Sound familiar? The grillage takes the form of questions between paragraphs, but also rears its head as queries that interrupt the flow of text The idea is to wake you up and remind you that you're not supposed to be memorizing, but rather thinking about the information flowing past your eyes, speculating about it, integrating it with what you know, what you'd like to know, and what you'd like to with all that knowledge (help sick people) It is crucial that you take advantage of the grillage How? When the book asks you a question, you'll usually find the answer in a footnote on the same page DON'T READ THE FOOTNOTE UNTIL YOU'VE ANSWERED THE QUESTION! Some of the answers are as simple as "C" or "No," and others are complex conceptual explanations In any case, take the time to formulate a thorough answer before you go to the footnote If you think you are too rushed to 11Waste" time in this way, I've got news for you: you are studying the wrong way The waste of time is memorizing trivial details The profitable time is pondering concepts, as you'll on the day of the MCAT Though you shouldn't read the footnotes too soon, be sure to read them eventually, as sometimes they contain important information or vocabulary not given in the main body of the text The companion volume to this text is the MCAT Science Workbook, containing lots of MCAT-style passages on a wide variety of subjects Real MCAT passages aren't always so cohesive, meaning they tend to integrate material from various different areas The passages in the Workbook also tend to be a bit harder, in the sense of factual and conceptual questions The factual questions are harder to help you study the information; the conceptual questions so that you can practice DO ALL OF THE PASSAGES Be sure to read the solutions They address the confusions of thousands of past students The most important advice I can give you about the MCAT and the application process is to stop thinking of it as "the MCAT and the application process," and start thinking of it as "Becoming a doctor." That way you'll realize that all this study isn't just a hoop to jump through, but rather a crucial foundation for the biomedical side of the doctor you are becoming I specify "the biomedical side" in recognition of the fact that there's much more to doctoring than biomedicine But don't get me started Once I made the book all-inclusive, I tried to make it as light and engaging as possible If at times you find the style flippant, please know that I don't intend any disrespect I know that I have the privilege of addressing the highest-level readership of any author, and I am honored to share in your learning I don't wish you luck in your medical career because you don't need luck All you need is to work hard, play hard, and read some good novels And take some time to travel before medical school And respect your patients DJP iv MCAT BIOLOGY Table of Contents Below each chapter title are listed the MCAT topics covered in that chapter These topics correspond to those given in the AAMC's MCAT Student Manual, in the section entitled MCAT Biological Sciences Topics, Biology Note: Important biological molecules are discussed in Chapter of the MCA T Organic Chemistry text in this MCAT Biological Sciences Review You may want to review that chapter before beginning-or refer to during-your study of MCAT Biology Molecular Biology Topic I Microbiology Topic II Generalized Eukaryotic Cells Topic Ill Genetics and Evolution Topic XI Nervous and Endocrine Systems Topics V and IVA Circulatory, Lymphatic, and Immune Systems Topic VI Digestive and Excretory Systems Topic VII Muscle and Skeletal Systems Topics VIII, IVB, and IVD Respiratory and Skin Systems Topics IX and IVC 10 Reproductive Systems and Development Topic X v PERIODIC TABLE OF THE ELEMENTS - He H 1.0 Li 6.9 11 Na 24.3 20 Ca 21 Sc 40.1 38 85.5 87.6 55 56 132.9 87 137.3 88 (223) 226.0 227.0 Cs Fr Sr Ba Ra 14.0 14 15 16 27.0 28.1 31.0 32.1 35.5 39.9 31 32 33 34 35 36 72.6 50 74.9 51 79.0 52 83.8 54 127.6 79.9 53 I 126.9 84 85 AI 39.1 37 Rb 12.0 16.0 13 12 Mg 19 10.8 45.0 39 y 88.9 57 La* 22 23 24 Cr 25 Mn 26 47.9 40 50.9 41 52.0 42 54.9 43 91.2 92.9 95.9 (98) 72 73 74 Ti Zr Hf 138.9 178.5 104 89 Act Rf (261) v Nb Ta w Tc 75 Re 28 55.8 44 58.9 45 58.7 46 101.1 102.9 106.4 76 77 78 Fe Ru Os Co Rh Db Sg 186.2 107 190.2 192.2 109 108 (262) (263) (262) (265) 58 59 140.1 90 Th 232.0 Pr Bh 60 Nd Hs 61 Pm 62 Sm 93 94 (231) (237) (244) 238.0 Np 30 Zn Ga 63.5 47 65.4 48 69.7 49 107.9 112.4 114.8 80 81 Cu Ag 79 Cd In Pt Au Hg Tl 195.1 197.0 200.6 64 65 157.3 158.9 96 97 98 (247) (247) (251) Ge Sn p As Sb 118.7 121.8 82 Pb 204.4 207.2 83 Bi 209.0 s Se Te Po F 19.0 17 Cl Br At (209) (210) Ne 20.2 18 Ar Kr Xe 131.3 86 Rn (222) Mt (145) u Pd 29 Si N (267) 140.9 144.2 91 92 Pa Ni lr 180.9 183.9 106 105 Ce t Mo 27 c 4.0 10 B Be 9.0 23.0 K 63 Eu 150.4 152.0 Pu 95 Am (243) vi Gd Cm Tb Bk 66 Dy 67 Ho 162.5 164.9 Cf 68 Er 69 Tm 70 Yb 71 Lu 167.3 168.9 99 100 101 102 103 (252) (257) (258) (259) (260) Es Fm Md 173.0 175.0 No Lr MCAT BIOLOGY TABLE OF CONTENTS MOLECULAR BIOLOGY PARTS AND 2: BIOCHEMISTRY PART 1: ENZYMES 1 The Kinetic Role of the Enzyme 1.2 Enzyme Structure and Function 10 1.3 Basic Enzyme Kinetics 15 PART 2: ENZYMES AND CELLULAR RESPIRATION 19 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Energy Metabolism and the Definitions of Oxidation and Reduction 19 Introduction to Cellular Respiration 21 Glycolysis 22 Fermentation 24 The Pyruvate Dehydrogenase Complex 26 -rhe Krebs Cycle 27 Compartmentalization of Glucose Catabolism in Eukaryotes 31 Electron Transport and Oxidative Phosphorylation 32 MOLECULAR BIOLOGY PARTS AND 4: GENE EXPRESSION 37 PART 3: DNA AND THE GENETIC CODE 38 3.1 DNA Structure 38 3.2 The Role of DNA 46 3.3 DNA Replication 51 PART 4: GENE EXPRESSION 58 4.1 RNA and Transcription 58 4.2 Transcription 59 4.3 Translation 68 vii MICROBIOLOGY 77 PART 1: VIRUSES 78 1.1 Viral Structure and Function 79 1.2 Bacteriophage Life Cycles 82 1.3 Viral Genomes 87 PART 2: PROKARYOTES 90 2.1 Bacterial Structure and Classification 90 2.2 Bacterial Growth Requirements and Classification 95 2.3 Bacterial Life Cycle 99 2.4 Genetic Exchange Between Bacteria 101 PART 3: FUNGI 104 3.1 Fungal Structure 104 3.2 Fungal Life Cycles 105 *PART 4: RECOMBINANT DNA 108 GENERALIZED EUKARYOTIC CELLS 113 Introduction 114 PART 1: THE ORGANELLES 115 1.1 1.2 1.3 1.4 1.5 1.6 The Nucleus 115 Mitochondria 119 Endoplasmic Reticulum 121 The Golgi Complex 123 Lysosomes 124 Peroxisomes 125 PART 2: STRUCTURAL ELEMENTS OF THE ANIMAL CELL 126 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Membranes of the Eukaryotic Cell 126 Passive Transmembrane Transport 130 Active Transport : 135 The Na+fK+ ATPase and the Resting Membrane Potential 136 Endocytosis and Exocytosis 138 Cell-Surface Receptors 139 The Cytoskeleton 141 Cell Adhesion and Cell Junctions 143 PART 3: THE CELL CYCLE AND MITOSIS 144 viii GENETICS AND EVOLUTION 149 PART 1: GENETICS 150 1 1.2 1.3 1.4 1.5 1.6 The Language of Genetics 150 Meiosis 155 Mendelian Genetics 160 Linkage 165 Sex Linkage and Pedigrees 171 Population Genetics 174 PART 2: EVOLUTION 178 2.1 2.2 2.3 2.4 Evolution by Natural Selection 178 The Species Concept and Speciation 182 Taxonomy 183 The Origin of Life 185 NERVOUS AND ENDOCRINE SYSTEMS 187 PART 1: NEURONAL STRUCTURE AND FUNCTION 188 1.1 1.2 1.3 1.4 Structure of the Neuron 188 The Action Potential 190 Synaptic Transmission 195 Summation 198 PART 2: ORGANIZATION OF THE HUMAN NERVOUS SYSTEM 199 2.1 Functional Organization 199 2.2 Anatomical Organization 202 PART 3: SENSATION 208 3.1 3.2 3.3 3.4 Types of Sensory Receptors 208 Gustation and Olfaction 209 Hearing and the Vestibular System 210 Vision: Structure and Function 212 PART 4: THE ENDOCRINE SYSTEM 216 4.1 Hormone Types: Transport and Mechanisms of Action 216 4.2 Organization and Regulation of the Human Endocrine System 218 4.3 Major Glands and Their Hormones 221 ix CIRCULATORY, LYMPHATIC, AND IMMUNE SYSTEMS 225 PART 1: THE CIRCULATORY SYSTEM 226 1.1 1.4 1.5 1.6 1.7 Components of the Circulatory System 226 The Heart 228 Hemodynamics 237 Components of Blood 240 Transport of Gases 243 Exchange of Substances Across the Capillary Wall 246 The Lymphatic System : 248 PART 2: THE IMMUNE SYSTEM 248 2.1 2.2 2.3 2.4 Innate Immunity 248 Humoral Immunity, Antibodies, and B Cells 249 Cell-Mediated Immunity and the T Cell 252 Others Tissues Involved in the Immune Response 253 DIGESTIVE AND EXCRETORY SYSTEMS 255 PART 1: THE DIGESTIVE SYSTEM 256 1.1 1.2 1.3 1.5 Overview of the G I Tract 256 The Gastrointestinal Tract 260 The Gl Accessory Organs 266 A Day in the Life of Food 269 Vitamins 271 PART 2: THE EXCRETORY SYSTEM 272 2.1 Overview 272 2.2 Anatomy of the Excretory System 275 2.3 Endocrine Role of the Kidney 284 X MUSCLE AND SKELETAL SYSTEMS 285 PART 1: MUSCLE 286 1.1 Skeletal Muscle 286 1.2 Cardiac Muscle Compared to Skeletal Muscle 294 Smooth Muscle Compared to Skeletal Muscle 295 PART 2: THE SKELETAL SYSTEM 298 2.1 2.2 2.3 2.4 2.5 2.6 Connective Tissue 298 Macroscopic Bone Structure 298 Microscopic Bone Structure 299 Cartilage 300 Bone Growth and Remodeling: the Cells of Bone 300 Ligaments, Tendons, and Joints 301 RESPIRATORY AND SKIN SYSTEMS 303 u PART 1: THE RESPIRATORY SYSTEM 304 1 1.2 1.3 1.4 1.5 Functions 304 Anatomy of the Respiratory System 304 Pulmonary Ventilation 307 Gas Exchange 311 Regulation of Respiration 314 PART 2: THE SKIN 315 2.1 Structure 315 2.2 Temperature Regulation by the Skin 316 xi 10 REPRODUCTIVE SYSTEMS AND DEVELOPMENT 319 PART 1: THE REPRODUCTIVE SYSTEMS 320 1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 The Male Reproductive System 320 Spermatogenesis 323 Development of the Male Reproductive System 326 The Androgens 328 The Female Reproductive System: Anatomy and Development 329 Oogenesis and Ovulation 331 The Menstrual Cycle 333 Hormonal Changes during Pregnancy 337 PART 2: DEVELOPMENT 338 2.1 2.2 2.3 2.4 2.5 Fertilization and Cleavage 338 Implantation and the Placenta 340 Post-Implantation Development 341 Differentiation 343 Birth and Lactation 344 xii Chapter 10 332 MCAT Biology The primary oocytes formed in a female embryo are frozen in prophase I of meiosis for decades, until they re-enter the meiotic cycle At this point a single primary oocyte per menstrual cycle will be ovulated, but the fate of most primary oocytes is death Once each menstrual cycle, several primary oocytes are triggered by hormonal changes in the woman's body to re-enter the meiotic process All of these primary oocytes are now committed to entering a competition, and all except one die This is a fascinating microscopic example of survival of the fittest The one that survives completes meiosis I, extruding the first polar body and becoming a secondary oocyte The secondary oocyte emerges from the ovary and enters the fallopian tube-it is ovulated • Is the secondary oocyte haploid?27 Another unexpected fact about oogenesis is that the secondary oocyte will never complete meiosis II unless it is fertilized by a sperm In other words, the second polar body is not extruded tJ from the developing egg cell until after a spem1 nucleus has entered the cell So each month, during menstruation, it is not a mature egg cell that is lost, but rather a secondary oocyte frozen in meiosis ~ II If and when fertilization does occur, the nuclei from the sperm and egg not fuse immediately-they must wait for the secondary oocyte to release the second polar body and finish \:") maturing to an ootid and then an ovum Finally, the two nuclei fuse, and a (2n) zygote is formed Facts About Oogenesis: ~L 'J ~ (,\lj ~I , ~\j· \, lr ~\ ~ \~ All gamete precursors (primary oocytes) are formed while a female is still an embryo in her mother's womb Primary oocytes are frozen in prophase I for decades Each meiotic division results in one viable egg precursor plus one polar body that dies ~ \J i" \ When the meiotic cycle is finally reactivated, compettion occurs and only one pnmar ~\'- 1J 1\ oocyte succeeds It releases the first polar body as it matures into a second~r which is ovulated Many other primary oocytes enter the competition but lose a Hence, many primary oocytes are lost with each menstrual cycle Secondary oocytes not finish meiosis II unless they are fertilized In other words, fertilization occurs before the egg precursor is mature When fertilization occurs, the egg and sperm nuclei not fuse until after the egg extrudes the second polar body and completes its maturation process to become a mature ovum Hence, the ootid is a zygote-precursor cell which contains separate sperm and egg nuclei 27 Yes After the first meiotic division, the cell is haploid; the homologous chromosomes have been separated (They are, however, still replicated, hence the reason for meiosis II.) \ !"(} r.\~t\1 ~~~P: ~~~~~ {$ ~\fj \ '~ MCAT Biology Reproductive System and Development 333 • When an oogonium undergoes meiosis, three cells result How many of these are eggs, and why only three cells result? (Meiosis results in four cells in the male )28 Before we move on to a discussion of the menstrual cycle, you will need more background information on oogenesis The primary oocyte is not an isolated cell It is found in a clump of supporting cells known as a follicle The follicle is comprised of a primary oocyte surrounded by granulosa cells, which assist in maturation [What is the male counterpart of the granulosa cell ?29] An immature primary oocyte is surrounded by a single layer of granulosa cells, forming a primordial follicle The primordial follicle matures into a primary follicle when the granulosa cells proliferate to form several layers around the oocyte, the oocyte itself forms a protective layer of mucopolysaccharides termed the zona pellucida, and the follicle is surrounded by interstitial cells termed thecal cells The thecal cells are found in the ovarian interstitium, between follicles [What cells in the male are thecal cells analogous to, and what hormone they respond to?30] Of the maturing follicles, only one progresses to the point of ovulation each month; all ~thers degenerate The mature follicle is known as a Graafian follicle During ovulation, the mature follicle bursts, releasing the secondary oocyte with its zona pellucida and protective granulosa cells into the fallopian tube At this point the layer of granulosa cells surrounding the ovum is known as the corona radiata Estrogen is made and secreted by the granulosa cells (with help from the thecal cells) during the first half of the menstrual cycle Both estrogen and progesterone are secreted during the second half of the cycle 1.7: The Menstrual Cycle Estrogen is a steroid hormone that plays an important role in the development of female secondary sexual characteristics, in the menstrual cycle, and during pregnancy [How does estrogen exert an effect on the cell?31] Progesterone is also a steroid hormone involved in the hormonal regulation of the menstrual cycle and pregnancy, but with different activities than estrogen During the menstrual cycle, estrogen is synthesized by the follicle, and both estrogen and progesterone are synthesized by the corpus luteum, a small body formed by the follicular cells remaining in the ovary after ovulation These hormones are not secreted at constant levels but in repeating cycles that are responsible for the menstrual cycle Only one egg results The three cells which result are two polar bodies plus one ovum There are only three because the first polar body does not divide (In meiosis in the male, both cells derived from the first meiotic division go on to divide.) 29 The cells which support and nurture developing spermatocytes are the Sertoli cells 30 They are analogous to the testicular interstitial cells of Leydig Both Leydig and thecal cells are stimulated by LH 31 A cytoplasmic receptor binds estrogen and binds to specific DNA elements in promoters and enhancers to regulate transcription 28 Chapter 10 334 MCAT Biology The menstrual cycle involves preparation of the endometrium of the uterus for potential pregnancy, followed by the shedding of the endometrium if pregnancy does not occur During the proliferative phase of the menstrual cycle, estrogen produced by the follicle induces the proliferation of the endometrium (Figure 6) After ovulation, the secretory phase occurs, in which estrogen and progesterone produced by the corpus luteum further increase development of the endometrium, including secretion of glycogen, lipids, and other material If pregnancy does not occur, the secretion of estrogen and progesterone decrease sharply, and the endometrial lining sloughs out of the uterus, producing the bleeding associated with the menstrual phase The menstrual cycle is then set to begin the proliferative phase and the rest of the cycle once again, continuing once every 28 days (approximately) from adolescence to menopause Figure 6: The Endometrial Cycle ,., ,., • :.!:.-::, ·: _ - , , .,., • • • ,., ,., ,., - c:.~:.~:.~~ - ··JJ• 'lo•"' , ~ ;.· , , t"•rl'• "•, , ··"~ .t"•rl'•rl'•, ,., , ,., ,., , Day of menstrual cycle 17 28 The phases of the cycle can also be described according to events occuring in the ovary (Figure 7) While menstruation is still occuring in the endometrium, the ovarian follicular phase begins, in which a primary follicle matures and secretes estrogen This estrogen stimulates a primary oocyte to proceed through meiosis I to meiosis II and causes the proliferative effects of ovarian estrogen on the endometrium In the ovulatory phase, a secondary oocyte is released from the ovary • What stage of development is the endometrium at when ovulation occurs?32 • Where is the secondary oocyte during the secretory phase?33 32 The endometrium is at the proliferative phase, under the influence of ovarian estrogen 33 The secondary oocyte is traveling down the fallopian tube toward the uterus If it fails to implant in the uterus, the secretory phase ends and menstruation begins 335 Reproductive System and Development MCAT Biology The luteal phase is the period in which the estrogen and progesterone secreted by the corpus luteum after ovulation stimulate the endometrial secretory phase If implantation of a fertilized embryo in the uterus does not occur, the corpus luteum degenerates and menstruation occurs • If estrogen and progesterone were given to a woman without cyclic variation, how would this affect n1enstruation ?34 Figure 7: The Endometrial and Ovarian Cycles { follicular phase ovanan cycle ovulatory phase , _ r/' - , ,p.,p P' ••• ,p , .·· ~ :~.-: ,; ••.J •.J ,~ Day of menstrual cycle 17 28 The anterior pituitary and the hypothalamus also play a role in the menstrual cycle by regulating the secretion of estrogen and progesterone (Figure 8) FSH and LH are secreted by the anterior pituitary in response to stimulation by GnRH from the hypothalan1us FSH and LH stin1ulate the secretion of estrogen and progesterone either by the follicular cells or the corpus luteum Secretion of GnRH, FSH, and LH is inhibited by high levels of estrogen and progesterone Under the influence of FSH, the ovarian follicular cells develop during the follicular phase and secrete estrogen Although high levels of estrogen inhibit LH secretion, the gradually increasing estrogen of the follicular phase stimulates a burst in LH secretion It is this sudden surge in LH that causes ovulation After ovulation, LH induces the follicle to become the corpus luteum and to secrete 34 Menstruation occurs because the estrogen and progesterone secreted by the corpus luteum decrease suddenly when the corpus luteum degenerates If estrogen and progesterone are kept at high levels, such as with a pill (or pregnancy), then menstruation will not occur Chapter 10 336 MCAT Biology estrogen and progesterone during the secretory phase If pregnancy does not occur, the high levels of estrogen and progesterone feedback to inhibit secretion of GnRH, FSH, and LH When LH secretion drops, the corpus luteum regresses, no longer secretes estrogen or progesterone, and menstruation occurs without stimulation of the endometrium by estrogen and progesterone • If LH levels remained high, how would this affect the secretion of estrogen and progesterone ?35 Figure 8: Pituitary and Ovarian Hormones of the Menstrual Cycle LH -· 17 28 Day of menstrual cycle • What would happen if the estrogen levels in a woman's blood were artificially caused to remain high for the entire month ?36 • What would happen if the artifical estrogen were suddenly taken away? 37 35 If LH levels remained high, the corpus luteum would not regress, and estrogen and progesterone would also remain high, thus maintaining the endometrium so that menstruation would not occur This is in effect what happens if an embryo is fertilized and implants, except the hormone in this case is not LH but hCG, human chorionic gonadotropin, an LH-like hormone (see the next section) 36 The woman would not ovulate That's what the birth control pill is: estrogen 37 The endometrium would slough off, and the woman would menstruate (This is why there are 21 pills of one color and pills of another color The pills are just "sugar-pills"-no estrogen If a woman took only the first kind of pill every day, she would never menstruate Also, the second kind of pill is actually unnecessary; these pills are present in order to help establish the habit of taking a pill every day.) 337 Reproductive System and Development MCAT Biology 1.8: Hormonal Changes During Pregnancy There are still a couple of points we have not made completely clear: How can pregnancy occur if the uterine lining is lost each month, and why does the body discard the endometrium? Recall that the physical reason for endometnal shedding is a decrease in estrogen and progesterone levels which occurs as the corpus luteum degenerates Why does the corpus luteum degenerate? Due to a decrease in luteinizing hormone Why does LH decrease? Due to feedback '- inhibition from the hig~ le~~~ of estrogen and progesterone secreted by theerPus lute~ Let's begin with why LH levels decrease During pregnancy, ovulation should be prevented -= - The way ovulation is prevented is that the constant high levels of estrogen and progesterone seen -· during pregnancy inhibit secretion of LH by the pituitary; no LH surge, no ovulation Constant fugh levels of estrogens inhibit LH release The result is pregnancy without contlnuea ovulation ;-_._, The secondary result is the one we were trying to explain: When the corpus luteum secretes a lot of estrogen and progesterone during the menstrual cycle, LH levels drop, causing the corpus luteun1 to degenerate The point is that the corpus luteum degenerates unless fertilization has occurred So how can pregnancy occur? If pregnancy is to occur, the endometriuin must be maintained, because it is the site of gestation, i.e., where the embryo lives and is nourished If fertilization takes place, within a few days a developing embryo becomes implanted in the endometrium, and a placenta begins to develop The chorion is a portion of the placenta which is derived fro_~!~~- Maintenance of the endometrium is accomplished by the chorion secreting a hormone -which can take the place of LH in maintaining the corpus luteum This hormone is called human chorionic gonadotropin, or hCG It is a~e - hormone that is very similar to both LH and FSH : -_-~~Z!l!!!!illlll-=::::::;::::= in structure This answers the question of how pregnancy can occur • Which of the following occur(s) during the menstrual cycle in1rnediately prior to ovulation?38 I A surge in luteinizing hormone release from the anterior pituitary II Completion of the second meiotic cell division by the oocyte III Shedding of the endometrium 38 Item I: True The LH surge causes ovulation Item II: False Meiosis I is completed prior to ovulation Meiosis II isn't completed until after fertilization Item III: False Ovulation occurs around day 14 of the cycle Menstruation begins at day Chapter 10 338 MCAT Biology • As a woman ages, the number of follicles remaining in the ovaries decreases until ovulation ceases At this point, termed menopause, the menstrual cycle no longer occurs Which of the following occur(s) during menopause?39 I FSH levels drop dramatically and stay low II Estrogen levels are abnormally high III LH levels are very high and stay high • Which of the following statements concerning the menstrual cycle is/are true ?40 I The proliferative phase of the endometrium coincides with the maturation of ovarian follicles II The secretory phase of the endometrial cycle is dependent on the secretion of estrogen from cells surrounding secondary oocytes III Luteinizing hormone levels are highest during the menstrual phase of the endometrial cycle Part 2: Development 2.1: Fertilization and Cleavage A secondary oocyte is ovulated and enters the fallopian tube It is surrounded by the corona radiata (a protective layer of granulosa cells) and the zona pellucida, also known as the vitelline layer (located just outside the cell membrane) The oocyte will remain fertile for about a day If intercourse occurs, sperm are deposited near the cervix, and are activated, or capacitated Sperm capacitation involves the dilution of inhibitory substances present in semen The activated sperm will survive for two or three days They swim through the uterus toward the secondary oocyte Fertilization is the fusion of a spermatozoan with the secondary oocyte It normally occurs in the fallopian tube In order for fertilization to occur, a sperm must penetrate the corona radiata and bind to and penetrate the vitelline layer It accomplishes this using the acrosome reaction The acrosome is a large vesicle in the sperm head containing hydrolytic enzymes which are released by exocytosis After the corona radiata has been penetrated, an acrosomal process containing actin elongates toward the vitelline layer The acroson1al process has bindin, a species-specific protein which binds to receptors in the vitelline layer Finally, the sperm and egg plasma membranes fuse, 39 In the absence of estrogen and progesterone secretion by follicles, there is no feedback inhibition of LH and FSH, so their levels are very high in postmenopausal women Hence, only item Ill is true Item I: True This is explained in the text Item II: False It is secretion of estrogen and progesterone by the corpus luteum which drives the secretory phase The corpus luteum is in the ovary, while the secondary oocyte is out in the fallopian tube Item III: False The luteinizing hormone level peaks during the proliferative phase, since this is when ovulation occurs 40 Reproductive System and Development MCAT Biology 339 and the sperm nucleus enters the secondary oocyte In about twenty minutes, the secondary oocyte completes meiosis II, giving rise to an ootid and the second polar body The ootid matures rapidly, becoming an ovum Then the sperm and egg nuclei fuse, and the new diploid cell is known as a zygote Penetration of an ovum by more than one sperm is known as polyspermy It is normally prevented by the fast block to polyspermy and the slow block to polyspermy, which occur upon penetration of the egg by a spermatozoan The fast block consists of a depolarization of the egg plasma membrane This depolarization prevents other spermatozoa from fusing with the egg cell membrane The slow block results from a influx caused by the initial depolarization The slow block is also known as the cortical reaction It has two components: swelling of the space between the vitelline layer and the plasma membrane, and hardening of influx has one other noteworthy effect It leads to a pH change within the vitelline layer The Ca2+ This in turn causes increased metabolism and protein synthesis, referred to as egg activation • Because a particular disease, a man produces sperm without acrosomes His spermatozoa are abnormal in that they:41 are immotile B cannot undergo capacitation C are incapable of fertilizing the egg can fertilize the eggs of many species • Which one of the following would NOT cause or indicate infertility? 42 A lack of progesterone secretion during the latter half of the menstrual cycle B Failure of mitosis to occur after the male pronucleus enters the ovum C Excessively acidic pH of vaginal secretions A decrease in the concentration of LH after ovulation 41 A: No The acrosome is in the head of the sperm and plays no role in motility B: No Capacitation is the activation of sperm which occurs when they enter the vagina It involves dilution of inhibitory substances present in semen, and other changes The acrosome is not relevant to this C: Yes Acrosomal enzymes (e.g., hyaluronidase) are necessary for penetration of the corona radiata, and the acrosomal process is necessary for binding to and penetration of the vitelline layer D: No The sperm would be incapable of fertilizing any eggs 42 A: No This would indicate that the corpus luteum was not behaving normally during the menstrual cycle, suggesting that ovulation had not occurred or that something else was wrong in the ovary B: No The male pronucleus just means the haploid sperm nucleus As discussed below, embryogenesis begins with cleavage, the mitotic division of the zygote; no mitosis, no embryo This definitely indicates infertility C: No Sperm are very sensitive to pH Abnormal acidity would damage the sperm D: Yes This normally occurs! LH levels fall due to the high levels of estrogen and progesterone secreted by the corpus luteum Chapter 10 340 MCAT Biology Cleavage The process of embryogenesis begins within hours of fertilization, but proceeds slowly in humans The first stage is cleavage, in which the zygote undergoes many cell divisions to produce a ball of cells known as the morula The first cell division occurs about 36 hours after fertilization [The morula is the same size as the zygote, which indicates that the dividing cells spend most of their time in what phases of the cell cycle?42 During cleavage of the zygote, homologous chromosomes physically interact with each other?43] As cell divisions continue, the morula is transformed into a blastocyst This process is known as blastulation The blastocyst consists of an outer cell niass surrounding a cavity, and an inner cell mass adhering to the inside of the outer cell mass at one end of the cavity The outer cell mass gives rise to the trophoblast, which will give rise to the chorion (the zygote's contribution to the placenta) The inner cell mass will become the embryo • If two inner cell masses form in the blastula, what will the result be? 44 2.2: Implantation and the Placenta The developing blastocyst reaches the uterus and burrows into the endometrium, or implants, about a week after fertilization The trophoblast secretes proteases that lyse endometrial cells The blastocyst then sinks into the endometrium and is surrounded by it, absorbing nutrients through the trophoblast into the inner cell mass The embryo receives a large part of its nutrition in this manner for the first few weeks of pregnancy This is why the secretory phase of the endometrial cycle occurs: endometrial cells store glycogen, lipids, and other nutrients so that the early embryo may derive nourishn1ent direCtly from the endometrium Later, an organ develops which is specialized to facilitate exchange of nutrients, gases, and even antibodies between the maternal and embryonic bloodstreams: the placenta Because it takes about months for the placenta to develop, it is during the first trimester (three months) of pregnancy that hCG is essential for maintenance of the endometrium (Section 1.8) • What happens if the corpus luteum is removed during the first trimester?45 42 They must spend most of their time during the S (synthesis) and M (mitotic) phases, skipping the G and G2 (gap or growth) phases 43 No Pairing of homologous chromosomes only takes place during meiosis, which only occurs during gametogenesis 44 The inner cell mass becomes the embryo Two inner cell masses derived from a single zygote and enclosed by the same trophoblast will result in a pair of identical twins sharing the same placenta 45 The woman menstruates, and the embryo is lost Remember, the role of hCG is to substitute for LH in stimulating the corpus luteum The role of the corpus luteum is to make estrogen and progesterone, which maintain the endometrium 341 Reproductive System and Development MCAT Biology During the last six months of pregnancy, the corpus luteum is no longer needed because the ·placenta itself s~s sufficient estrogen ailCfProgestero~~ for rriaintenance of the endometrium The development of the placenta involves the formation of placental villi These are chorionic projections extending into the endometrium, into which fetal capillaries will grow Surrounding the villi are sinuses (open spaces) filled with maternal blood [Does oxygen-containing blood pass from the mother into the developing fetus?46] The embryo is not the only important structure derived from the inner cell mass There are three others: amnion, yolk sac, and allantois The amnion surrounds a fluid-filled cavity which contains the developing embryo Amniotic fluid is the "water" which "breaks" (is expelled) before birth The yolk sac is important in reptiles and birds because it contains the nourishing yolk Mammals not store yolk ~k sac is importaut because.J.tis the first site of red blood cell synthesis in the embryo Finally, the allantois develops from the embryonic gut and forms the blood vessels of < - - - - · - - - - - - · - - - - - - - - · the umbilical cord, whichtraflSPort blood between embryo and placenta • Each of the following has the same genome EXCEPT:47 A B C D Chorion Amnion Yolk sac Endometrium 2.3: Post-Implantation Development We have examined embryogenesis from fertilization through blastulation The next phase is gastrulation Gastrulation is when the three primary germ layers-the ectoderm, the mesoderm, and the endoderm-become distinct In primitive organisms, the blastula (equivalent to blastocyst) is a hollow ball of cells, and gastrulation involves the invagination (involution) of these cells to form layers Imagine pushing your fist into a big soft round balloon to create an inner layer (contacting your fist) and an outer layer (contacting the air) The inner layer is the endoderm, and the outer layer is the ectoderm The mesoderm (middle layer) develops from the endoderm The cavity (where your fist is) is primitive gut, or archenteron The opening (where your wrist is) is the blastopore, and will give rise to the anus The whole structure is the gastrula (Don't be confused: The gastrula has a blastopore; the blastula has no opening.) 46 No The placenta is like a lung in that it facilitates exchange of substances between the two bloodstreams without allowing actual mixing 47 A, B, and C: No, all are extraembryonic membranes derived from the inner cell mass as discussed in the paragraph preceding the question Hence, all have the same genome as the embryo This genome has information from both the mother and the father D: Yes This is part of the mother's uterus, and thus has genetic information only from the mother( Chapter 10 342 ::::J ::f MCAT Biology In humans, things are a little different The gastrula develops from a double layer of cells called the embryonic disk, instead of from a spherical blastula But the end result is the same: three _} layers You need to know ~parts of the human body are derived from each layer .!It- t;;:) ~ ~ ( ECTODERM -5 'f • Entire nervous system • Posterior pituitary, adrenal medulla • Cornea & lens • Epidermis of skin & derivatives (hair, nails, sweat glands, sensory receptors) • Nasal, oral, anal epithelium MESODERM • All muscle, bone, & connective tissue • Entire vascular & lymphatic system, including blood • Urogenital organs (kidneys, ureters, gonads, reproductive ducts) • Dermis ENDODERM • GI tract epithelium (except mouth & anus) • GI glands (liver, etc.) • Respiratory epithelium • Epithelial lining of urogenital organs & ducts • Anterior pituitary Pay attention to what types of thing are derived from each layer, and you'll see that it's very easy to memorize One key thing to note is that ectoderm and epithelium are not synonymous Epithelium outside the body (epidermis) is derived from ectoderm, but epithelium inside the body (gut lining) comes from endoderm • Which of the following statements is/are true?4 I Oxygen must diffuse across the chorionic membrane to reach the fetus from the mother II Transplantation of cells from the trophoblast of one embryo to the trophoblast of another embryo will result in an infant with a mixed genetic composition III All of the cells of the blastocyst are functionally equivalent The next step after gastrulation is neurulation, the formation of the nervous system It proceeds by the invagination and pinching off of a layer of ectoderm along the dorsum (back) of the embryo to form the dorsal neural groove This gives rise to the neural tube, which gives rise to the brain and spinal cord The formation of the neural tube is induced by instructions from the underlying notochord, which is mesodermal in origin It gives rise to the vertebral column Other ectodermal cells migrate through the body to form peripheral nervous system ganglia Item I: True The chorion is part of the placenta Item II: False The trophoblast is derived from the outer cell mass and gives rise only to the chorion The embryo is derived entirely from the inner cell mass Item III: False The trophoblast and the inner cell mass are both components of the blastocyst, and they have very different roles 48 Reproductive System and Development MCAT Biology 343 Neurulation is one component of organogenesis, the development of organ systems By the eighth week of gestation, all major organ systems are present, and the embryo is now called a fetus Even though the developmental process has attained staggering complexity, by the end of the first trimester the fetus is still only em long [During which trimester is the developing human most sensitive to toxins such as drugs and radiation?49] • A radioactive dye is detected only in the cells of placental villi Weeks earlier, it must have been injected into the:50 A inner cell mass B trophoblast c endometrium D zygote • During gastrulation, tissues derived from the trophoblast move inward to form the lining of the primitive gut?51 2.4: Differentiation The specialization of cell types during development is termed differentiation because as cells specialize they become different from their parent cells and from each other By specializing, a cell becomes better able to perform a particular task, while becoming less adept at other tasks For example, a sensory neuron is the best vehicle for the transmission of a nerve impulse over great distances, but is quite incapable of obtaining nourishment on its own, or even of reproducing itself Primitive cells in an early embryo have the potential to become any cell type They are known as totipotent cells There is a certain point in the development of a cell at which the cell fate becomes fixed The cell is said to be determined Determination precedes differentiation This means a cell is determined before it is visibly differentiated Determination can be induced by a cell's environment, such as exposure to diffusible factors or neighboring cells, or it can be preprogrammed 49 During the first trimester, when the organs are being formed 50 A: No This gives rise to the embryo B: Yes This gives rise to the chorion, which in turn gives rise to the placental villi C: No The villi are on the embryo's side of the placenta The mother contributes blood sinuses D: No Injecting the zygote would indeed lead to detection of dye in the villi, but also in the other extraembryonic membranes and also in the embryo itself 5l No Gastrulation involves only cells derived from the inner cell mass Chapter 10 344 MCAT Biology • During early embryonic development, cells near the developing notochord undergo an irreversible developmental choice to become skeletal muscle later in development, although they not immediately change their appearance This is an example of which of the following?52 A Determination B Differentiation c Totipotency D Induction There is such a thing as dedifferentiation This is the process whereby a specialized cell unspecializes and may become totipotent If a dedifferentiated cell proliferates in an uncontrolled manner, the result can be cancer The most important lesson you can learn from the notion of dedifferentiation is that every cell has the same genome The specialization of cell types is a function of things in the cytoplasm and maybe proteins and RNA in the nucleus, but no genetic changes normally take place during development and differentiation • Can you think of two exceptions to this rule, where a particular cell type hormally has a unique genome?53 2.5: Birth and Lactation The technical term for birth is parturition It is dependent on contraction of muscles in the uterine wall The very high levels of progesterone secreted throughout pregnancy help to repress contractions in uterine muscle, but near the end of pregnancy uterine excitability increases This increased excitability is likely to be a result of several factors, including a change in the ratio of estrogen to progesterone, the presence of the hormone oxytocin secreted by the posterior pituitary, and mechanical stretching of the uterus and cervix Weak contractions of the uterus occur throughout pregnancy As pregnancy reaches full term, however, rhythmic labor contractions begin It is thought that the onset of labor contractions is the result of a positive feedback reflex: The increased pressure on the cervix crosses a threshold that causes the uterine contractions to increase in intensity, creating greater pressure on the cervix that stimulates still stronger contraction Stretching the cervix also causes the posterior pituitary to increase the secretion of oxytocin 52 A: Yes A cell whose fate is fixed is said to be determined B: No Since the cell's appearance hasn't changed, it isn't differentiated yet C: No Since the cell is destined to become muscle, it is no longer totipotent (it can't become a nerve, for example) D: No Although the question states that the cells are located near the notochord, it does not say whether this location is the reason for their determination They still might be cytoplasmically determined 53 One exception is B cells and T cells of the immune system They undergo gene rearrangements in the process of attaining antigen specificity The other exception is gametes They have unique genomes because of 1) reductive division with independent assortment, and 2) recombination MCAT Biology Reproductive System and Development 345 The first stage of labor is dilation of the cervix The second stage is the actual birth, involving movement of the baby through the cervix and birth canal, pushed by contraction of uterine (smooth) and abdominal (skeletal) muscle The third stage is the expulsion of the placenta, after it separates from the from the wall of the uterus Contraction of the uterus after birth minimizes blood loss During pregnancy, milk secretion would be a waste of energy, but after parturition it is necessary During puberty, estrogen stimulates the development of breasts in women The increased levels of estrogen and progesterone secreted by the placenta during pregnancy cause the further development of glandular and adipose breast tissue But while these hormones stimulate breast development, they inhibit the secretion of milk After parturition, the levels of estrogen and progesterone fall and milk secretion begins Prolactin, an anterior pituitary hormone, is secreted in large amounts prior to parturition and is responsible for the actual stimulation of milk production by the breasts Every time suckling occurs, the pituitary gland is stimulated by the hypothalamus to release a large surge of prolactin, prolonging the ability of the breasts to secrete milk If the mother stops breast-feeding the infant, prolactin levels fall and milk secretion ceases The converse is also true: Milk secretion can continue for years, as long as nursing continues The breasts not leak large amounts of milk when the infant is not nursing This is because the posterior pituitary hormone oxytocin is necessary for milk let-down (release) Oxytocin is also released when suckling occurs 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ... section entitled MCAT Biological Sciences Topics, Biology Note: Important biological molecules are discussed in Chapter of the MCA T Organic Chemistry text in this MCAT Biological Sciences Review... crucial foundation for the biomedical side of the doctor you are becoming I specify "the biomedical side" in recognition of the fact that there's much more to doctoring than biomedicine But don't... to review that chapter before beginning-or refer to during-your study of MCAT Biology Molecular Biology Topic I Microbiology Topic II Generalized Eukaryotic Cells Topic Ill Genetics and Evolution