Lecture Notes III I. Energy Releasing Mechanisms A. Anaerobic – O2 not required 1. Glycolysis i. Alcoholic Fermentation – Yeast CO2 + Ethanol (ethyl alcohol) ii. Lactate fermentation – complicated animals lactic acid formed iii. Excretion of toxins in anaerobic pathways B. Aerobic respiration 1. Glucose as common metabolite – available from foods, converted from other monosaccharides, cleaved from disaccharides, glycogen & starch 2. C6H12O6 + 6O2 6CO2 + 6H2O + ATP (max yield of 36 ATP) via one of two pathways – glycolysis & oxidative phosphorylation i. Glycolysis a. The anaerobic phase: Each glucose produces 2 pyruvate molecules b. For each glucose 2ATP must be used to di-phosphorylate the glucose c. 4ATP are produced – resulting in net gain of 2ATP d. Energy associated with the hydrogen carried on 2 NADH carriers 3. Preparatory steps to the Krebs Cycle (TCA, Citric Acid Cycle) i. The two (3-carbon pyruvates) are converted to two (2-carbon) activated acetylCoenzyme-A complexes ii. This produces two CO2 molecules as by-product iii. And releases the energy of two NADH carriers iv. This “prepares” the Acetyl-CoA for entry into the Krebs cycle 4. Krebs Cycle – cyclic pathway that takes in the 2carbon Acetyl CoA and removes its carbons, hydrogens and electrons i. Products are 2CO2, 3NADH, FADH2 and an ATP by substrate level phosphorylation ii. Cycle cranks twice for each glucose that enters iii. Takes place in the mitochondrial inner compartment 5. Oxidative (Electron transfer) Phosphorylation – occurs through action of transmembrane enzymes in
the cristal of the mitochondria – Uses energy from H+ and their associated electrons brought by the carriers NADH and FADH2 i. Chemiosmosis – ability of certain membranes to use chemical energy to pump hydrogen ions and then harness the energy stored in the H+ gradient to drive cellular work (ATP synthesis) – in this example: turns 2NADH & 2 pyruvates from glycolysis into 2FADH2 & 2 Acetyl-CoA ii. NADH & FADH2 give up their electrons, which power H+ pumps pushing the free hydrogen outside the mitochondrial matrix – this forms an electrical & concentration gradient of H+ ions. These H+ ions flow back through ATP synthase, powering ADP + Pi ATP iii. Oxygen is the final e- acceptor, without which the entire process backs up to the pyruvate, forcing the system into anaerobic respiration as lactate (as pyruvate ↔ lactase, via LDH) iv. Energy from 1 NADH in Krebs 3 ATP | 1 FADH2 = 2 ATP v. Thus in aerobic respiration: 1 molecule glucose = Glycolysis SLP. – 2 ATP, Krebs SLP. – 2 ATP, 6NADH in Krebs – 18 ATP, 2NADH from glycolysis – 4 ATP, 2FADH2 from Krebs – 4 ATP, 2NADH in pyruvate to Acetyl CoA stage – 6 ATP = 36 total ATP II. DNA Replication (Experiments) A. Frederick Griffith – realized there was a transfer of genetic material from one strain of bacteria to another strain: 1. Mouse bacterial infection: 2. Concluded – living avirulent strain takes in the gene for production of smooth coated bacteria that is virulent: Thus the rough coated (avirulent) bacteria is TRANSFORMED into smooth coated (virulent) B. Hershey-Chase Experiments – Questioned: What is the genetic material being transferred 1. Used bacteriophage virus consisting only of a protein coat and a DNA core 2. Used radioactive isotopes of Sulfur (present only in the protein coat) and Phosphorus (only present in DNA) to determine whether the genetic information was in the protein, the DNA or both. 3. Determined it was the DNA which carried the genetic material. C. Watson, Crick, et. Al. (especially Franklin) 1. Determined, through X-ray crystalography and advanced mathematical calculations that DNA is shaped in a double helix. (Strands are antiparallel)
2. Double helix consists of alternating phosphate-sugar “rails” with nitrogenous base “rungs” i. Adenine/Guanine – Purines (double ringed bases) ii. Cytosine/Thyamine – Pyrmidines (single ringed bases) iii. C/G – 2 Hydrogen bond attachment, A/T – 3 H bond attachment 3. Chargaff’s Rules: States that A/T, G/C must form “rails” in the double helix; the double rings are each matched with a single ring. III. DNA Replication: (Chs 13/14) A. Meselson & Stahl – Now that DNA is known to be the purveyor of genetic information being passed on, how is DNA replicated? 1. 3 Models from which to chose; conservative, dispersive & semi-conserv. 2. Parent generation grown in heavy nitrogen (N15) while subsequent R1 & R2 generations grown in ordinary nitrogen (N14) 3. R2 Generation then centrifuged to find out where the DNA would end up, telling them which model was correct. (All at the same place for dispersive, two distinct places in R1 for conservative, two distinct places in R2 but not R1 for semi-conservative) B. Ribose/Deoxyribose: 1. Deoxyribose has only an H at the 2’C instead of an OH. 2. Ribose has an OH on the 2 C 3. Notice: 3’ & 5’ Carbon attachment sites along which replication occurs: i. End of DNA rail is the 3’ end – sequence is 3C-P-5C-P-3C-P5C-P-3C... C. Activity at replication (replication fork – all takes place during STAGE S of interphase) 1. Helicase activity unwinds the double-helix prior to replication (at the V of the fork) 2. Complex enzyme DNA polymerase unwraps DNA & begins assembling along leading strand i. DNA polymerase is only able to build new DNA in direction from 3’ to 5’ along the parent strand. a. DNA polymerase releases two phosphates from a free floating nucleotide base. b. Energy released by this drives the attachment of the remaining P to an OH hanging off the 3’ C sugar of the preceding “rung” ii. Thus, one strand can be replicated smoothly (leading), the other strand cannot (lagging) 3. A “chunk” of RNA Primer attaches along the 2nd parent (lagging) strand i. RNA primer attaches to the lagging strand, allowing DNA polymerase to build “chunks” of DNA along that strand. ii. These chunks being build from RNA primer by DNA polymerase are Okazaki fragments iii. Okazaki fragments sewn together by DNA ligase
iv. The DNA contains an initiation and termination site, allowing mRNA to know where to start & stop 4. After this ligase “sewing” action there are two strands of DNA coming out of the S phase as sister chromatids D. DNA Repair 1. Conducted by specialized ligases and polymerases 2. Failure of these repair mechanisms is thought to be a cause of aging E. Use of DNA information in the cell: 1. Can only be done in G1 & G2 as DNA cannot control the functions of the cell while it is replecating or condensed into chromosomal form. 2. Use of the DNA material in the cell requires “reading” the language of DNA and translating it into the language of protein structure
IV. Transcription/Translation A. Transcription – the production of mRNA in nucleus. mRNA then leaves the nucleus, traveling to the ribosomes (in the rough ER), where Translation occurs. 1. Translation – the production of polypeptide chains at the ribosomes B. Classes of RNA 1. mRNA – (messenger) Carries the coding sequence to build a protein. 2. rRNA – (ribosomal) Major structural elements of ribosomes. Along with proteins rRNA molecules make up the ribosomes on which protein synthesis occurs 3. tRNA – (transfer) Specialized RNA molecules that deliver specific amino acids to the ribosomes for insertion into a growing polypeptide (protein) in the sequence specified by the mRNA 4. All transcribed from DNA, thus all produced in the nucleus C. Transcription Process – Initiated at a promoter; a base sequence on the DNA which signals the start of a gene 1. Differs from DNA replication in 3 ways: i. Only part of one DNA strand, not the whole molecule, is unwound and used as the template ii. The enzyme RNA polymerase, not DNA polymerase, adds ribonucleotides one at a time to the end of a growing strand of RNA iii. Unlike DNA replication, transcription results in a single unbound strand of RNA, not a H bonded double strand of DNA. 2. Initiated at promoter RNA polmerase enzyme mRNA molecule complementary to the DNA base sequence 3. mRNA must go through a maturation process before serving as a template for protein production i. Non-coding portions of mRNA (introns) are enzymatically “snipped” out ii. A tail and a cap are also attached to the mRNA that help it function at the ribosome D. Translation Process 1. After maturation, mRNA travels along ER to the ribosome where it serves as a template for protein manufacture i. Transcription produces the mRNA whose nucleotide base sequence tells the ribosome what the amino-acid sequence should be. The amino acid sequence determines the (primary) structure of the protein. Primary structure of protein determines quaternary structure of protein, which determines function. 2. Nucleotide base sequence on the mRNA is read three at a time (triplet code – or CODON) i. Because there are 4 bases at each position and 3 positions in a codon, there are 43= 64 possible codons, but only 21 different amino acids produce all proteins in the human body.
a. AUG – start codon | UAA, UAG & UGA serve as stop codons b. Thus 60 codons left over allowing some codons to code for the same amino-acid. c. This phenomena is knows as “Wobble Effect” 3. tRNA – specific to 3 complementary base sequence found on mRNA in ribosome AND contains an amino-acid binding site, thus: a specific amino-acid is linked to tRNA that is specific to the nucleotide base sequence. (tRNA’s complementary base sequence allowing attachment and addition of amino acid known as ANTICODON) 4. After tRNA attaches its amino acid, it leaves the ribosome re-entering the cytoplasm pool of amino-acids to reattach the appropriate amino acid to its specific bonding site 5. Ribosome itself consists of two subunits (Large & Small) i. These subunits of the ribosome are assembled in the nucleus and transported separately to the cytoplasm where they are assembled and attached along the rough ER E. 3 Stages of Transcription 1. Initiation - Initiator tRNA binds to a small ribosomal subunit, creating a small subunit/tRNA complex i. tRNA/subunit complex attaches to mRNA ii. The start codon matches up with the initiator tRNA anticodon iii. The large ribosomal subunit joins and initiation comples 2. Elongation – the next tRNA (after the previously mentioned initiator tRNA & mRNA trans.) with its matching anticodon loads onto the second (“A”) site of the ribosome and the mRNA transcript is advanced forward one codon in the ribosome leaving the most recently attached tRNA at the first attachment site (P) and an open second attachment site (A) on the ribosome i. Now the next tRNA with its attached amino acid can link with the mRNA transcript at the “A” site ii. Peptide bond between the two amino acids at the P and A sites is created, elongating the polypeptide iii. The process then repeats 3. Termination – stage in which a stop codon moves onto the platform. i. Stop codon triggers the release of the protein and the mRNA from the ribosome ii. mRNA can be used to generate another protein molecule or broken down to make another mRNA transcript V. Chapter 11 – Genetics A. Mendel – Using pea plants found indirect but observable evidence of how parents transmit genes to offspring 1. Mendel was able to track the traits of his pea plants and was able to discern the patterns showing clearly observable patterns tracing the inheritance of traits B. Basic Genetics: 1. P1 = Parent Generation | F1 = first generation offspring | F2 = 2nd generation offspring 2. Monohybrid cross = AA x aa | Dihybrid cross = AABB & aabb = AB x ab 3. Genotype – genetic composition | Phenotype – observed condition/composition 4. Rh factor in human blood (+ or -) signifying the presence of absence of the Rh or D antigen in the blood. Rh negative mother having an Rh + child can develop antibodies against Rh+ and eventually destroy those cells. 5. Complete dominance = RED x white = RED | Incomplete = RED x white = Pink (because of multiple alleles coding for the same trait)
VI. Structural Heirarchy A. Cells Tissues Organs Organ Systems Organism B. Tasks of Physiology – Maintenance of homeostasis, acquisition of O2 & nutrients, excretion of waste, protection from attack/injury/disease, reproduction C. Tissues 1. Epithelial – exposed to “outside”, surface covering (skin, trachea, etc), can be glandular 2. Connective – Living Cells in a non-living matrix that the living cells themselves secrete 3. Muscle – contractile tissue 4. Nerve – Rapid & specific communication D. Cell Junction Types 1. Tight Junctions – Isolate deeper layers of a tissue from the surface i. Layers of protein fibers act to hold cells together – make it difficult for objects at surface to work their way between the cells into deeper tissue layers (Gut, trachea, bladder) 2. Adhering Junctions – Great physical strength holding cells together | Cells held together by protein plaque (Muscle, skin, tendons, etc) 3. Gap Junctions – rapid ion transfer between cells (allows for carrying of electrical signal through tissue ) allow polar ions to pass through cell membrane (heart) E. Epithelium 1. Apical – at top | Basal – at bottom…usually rests on a basement membrane which “glues” epithelium in place 2. All epithelium is avascular…blood supply is in the basement tissue 3. Subclasses of Epithelium i. Lining/Surface – Gut, Respiratory tract, Urniary Tract ii. Glandular – All exocrine glands; sweat, acid producers in stomach, bile in liver, etc 4. Cell Shapes i. Squamous (flat) – Designed to reduce friction and often to be worn away. Provides for a large surface area and thus easily diffuses ii. Cuboidal – Large internal volume – often have many mitochondria and golgi bodies. High producers & metabolically active iii. Columnar – have an apical and basal surface: apical sometimes has cilia on it, large cellular volume and are good secretory cells iv. Cells may be in a singler layer (simple) or stacked (stratified) F. Connective Tissue 1. Large variety of tissue types and levels of vascularity i. Avascular (cartilage) to highly vascular (bone) 2. All characterized by having living cells suspended in a non-living matrix which the cells themselves produce 3. Dense Irregular Connective Tissue: Human Skin, intestinal muscles, etc; matrix packed with many fibroblasts and collagen fibers. 4. Dense Regular Connective Tissue: Orderly rows of fibroblasts between parallel, tightly packed bundles of fibers. (Tendons and ligaments) 5. Loose connective tissue (ex. Dog Skin): Framework tissues for many organs and tissues (matrix often semi-fluid) 6. Specialized Connective Tissues
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i. Cartilage – chondroblasts secrete a matrix which is hyaline, avascular. Rubbery, compression resistant ii. Bone – Osteocytes work to maintain a calcium phosphate and collagen matrix iii. Adipose – fat tissue, used as an energy reservoir iv. Blood* - Living cells in a plasma matrix [don’t entirely fit the description perfectly as plasma isn’t made by the blood] Muscle - Can be very long & skinny cells 1. Skeletal (voluntary) – Striated, electrically insulated cells clustered in motor units activated by a motor neuron. Rapid contraction and relaxation. Multi-nucleated (therefore cannot mitose) to control action over the long length of the entire cell 2. Cardiac – Striated, branched cells, joined by gap junctions. Slower than skeletal muscle but still rapid (<1 second). No motor neurons, no motor units. Much smaller than skeletal muscle, single nucleus. 3. Smooth – Involuntary: non-striated. Muscle of internal organs, arterial walls, sphincters, internal muscles of the eye. Slow gradual relaxation. Capable of sustained (over multiple hours) contraction Neurons (Nerve Cells) 1. Contain an input reigon and an output reigon. 2. Do not mitose 3. Electrically responsive: maintain a resting electrical gradient across the membrane 4. Consists of: Cell body, Receptive area (dendrite), and transmission reigion, usually a long axon. 5. Electrical Chemical Electrical charges 6. Transduction at the synapse ensures one-way transmission; permits integration Germ Layer Fates 1. Endoderm – Lining of respiratory and digestive tracts (pancreas, liver, etc) 2. Mesoderm – Skeletal muscle, outer covering of internal organs, blood vessels & heart, notochord 3. Ectoderm – all nervous tissue, epidermis, skin and hair epithelium, inner ear, retina of eye, etc. Started out ou outside of “blastula” and migrated inward during development Human Organ Systems 1. Integumentary – Skin and associated organs | Skeletal | Muscular | Nervous | Endocrine – General chemical signaling| Cardiovascular | Lymphatic – immuno-related & returns fluids to blood stream | Respiratory | Digestive | Urinary | Reproductive Cavities of the Human Body 1. Dorsal – Contains cranial & spinal cavities 2. Thoracic – Contains pleural spaces (lungs) and mediastinum (heart, trachea, esophagus, etc) 3. Abdominopelvic – From the diaphram down (stomach, liver, intestines, bladder, etc) Planes/Positions of the Body 1. Anterior/Posterior – front/back 2. Superior/Inferior – above/below 3. Dorsal/Ventral – top/bottom of 4 legged animal (fish) 4. Distal/Proximal – far/close with respect to body attachment (extremities) 5. Medial/Lateral – close/far with respect to the trunk 6. Transverse – Cross-section at waist
7. Frontal Plane – Shoulder to shoulder, parallel to width of body. (Coronal when referring to the head) 8. Saggital Plane – Division into left and right sides along the symmetrical axis (mid-saggital) M. Homeostasis – active maintenance of a constant internal environment N. Feedback 1. Negative Feedback Loop – Inverse relationship: fall in temp/pH = response = rise in T/pH i. Components: Sensor to determine the controlled variable, controller/integrator to connect sensor to effector, effector which affects the controlled variable ii. Set point – the level that is maintained 2. Positive Feedback Loop – Direct relationship: rise in tepm/pH = response = further rise i. Ex: Contractions at childbirth, nerve firing, etc 3. Negative feedback loop allows for the maintence of stablity provided the disturbance is not too large and overpowering for the functional response mechanisms VII.Nerve Cells – Ch. 34 A. Structure: 1. Input zone: dendrites, cell body 2. Couducting zone: Axon 3. output zone: Axon endings (terminals) B. Transduction: Transfer of signal from one form to another: 1. Chemical electrical Chemical 2. (input/trigger) (axon) (output zone) C. Ionic Distribution across cell membrane results in most cells carrying a slight negative charge 1. Neuron Cell Membrane: selectively permeable, depending upon charge/size, etc. i. Either active or passive channels (leakage channels) 2. Membrane potential – the electrical charge generated by the slightly negative charge inside the cell compared to the outside of the cell 3. A change in voltage opens some of the selective (active) channels