Biochem Final Review PDF

Lecture 13 - Protein Metabolism Explain the details of the genetic code Translation: making proteins from mRNA using tRNA Higher error rate than DNA replication ○ Proteins don’t last so they don’t need to be perfect, just be able to function Very expensive Codon = triplets of nuc...

Lecture 13 - Protein Metabolism Explain the details of the genetic code Translation: making proteins from mRNA using tRNA Higher error rate than DNA replication ○ Proteins don’t last so they don’t need to be perfect, just be able to function Very expensive Codon = triplets of nucleotide that are coding for amino acids Genetic code is degenerate = redundant = multiple codon code for the same thing due to: Wobble Hypothesis: 3rd position of codon is much less specific and binds more loosely Genetic reading frame: 3 nucleotide sequence that make up a codon Frameshift mutation shifts the reading frame and results in completely altered translational product Open reading frame: sequence of DNA & RNA that can be coded Start codon, internal codons, stop codon, exons ○ Introns = stay in AUG: initiation codon Also codes for fMet ○ Other AUG are just regular Met UAA/UGA/UAG: termination/stop codons Doesn’t code for anything else tRNA: RNA that binds amino acids to make protein CCA at amino acid arm Anticodon arm is antiparallel alignment ○ Conservative substitution: subbing 1st base of anticodon, creates AA with similar properties ○ 1st position of codon is the 3rd position of codon ATP required Ribozymes: RNA with catalytic activity Their own proteins Bacterial ribosomes: 30S + 50S = 70S  Odd Eukaryotic ribosomes: 60S + 40S = 80S Even Ribosome made of A, P, and E sites Ribosomes have proofreading ability Detail the mechanisms of protein synthesis and associated pharmacology Translation in 3 steps: Initiation, elongation, and termination Goes 5’-3’ Bacterial Initiation Complex: Shine-Dalgarno sequence guides AUG to P site to bind with fMet IF3 prevent 30s & 50s from prematurely combining Eukaryotic Initiation: PABP [Poly(A) binding protein] goes at 3’ end and cap goes on other end to circularize mRNA More complicated than bacteria Elongation: EF-Tu brings aminoacyl-tRNA to A site at the cost of 1 GTP. Peptidyl transferase forms peptide bond between AA at A and P site, AA chain is transfered at A site and deacylated tRNA leaves at E site Termination: Signaled by stop codon, termination factors dissociate the ribosome and tRNA Eukaryotes: eRF Bacteria RF1-3 Cost 4 phosphate equivalents to make each peptide bond Polysomes are used by bacteria to accelerate protein production Translation & transcription happening together Posttranslational modifications are needed by some proteins to get to final conformation Acetylation Methylation Some proteins are made from precursor polypeptides Insulin! Pharmacology Puromycin ○ Inhibitory that terminates polypeptide synthesis ○ Made by mold Tetracyclines ○ Inhibits bacteria by blocking A site & aminoacyl-tRNA binding Chloramphenicol ○ Blocks peptidyl transfers ○ Doesn’t affect eukaryotes Cycloheximide ○ Blocks 80S ribosomes (eukaryotic) ○ Doesn’t affect Bacteria Streptomycin ○ Causes misreading at low concentration ○ Inhibits initiation at high concentrations Describe protein targeting, degradation and HbA1c Endoplasmic Reticulum: organelle where synthesis, folding, and transportation of proteins and lipids SRP cycle: halts elongation of protein chain synthesis Golgi : Packing and processing of molecules NLS targets protein to nucleus Proteins come in on cis side, leave on the trans side Cells membranes uses vesicles formed by dynamin to receive proteins Clarthorin & cavlevolin Ubiquitin: protein that selects which proteins are destroyed by 26S proteasome Glucose binds to hemoglobin of RBC in concentration dependent manner A1c 5.7-6.4 = pre-diabetic >6.5 = diabetic pink->white colored flowers Codominance: phenotype of hetero is mixture of both phenotypes  ○ Red with white patches on flowers Penetrance: % of individuals of a genotype showing the phenotype Expressivity: degree of the trait being expressed ○ In terms of dominance Lethal Allele: Nonviable at an early development stage, effects the genotypic/phenotypic ratios Can be heterozygous if dominant Gene interactions: effects of gene depend on presence of gene elsewhere Epistasis: One gene mask/modifiers the another gene ○ The genes don’t have to share a phenotype ○ Genomic imprinting: depends on which parent the expression is from Complementary: two genes are needed to make specific trait Duplicate gene interaction: multiple genes have same function but only one copy is needed Polygenic inheritance: Addictive effect of multiple genes Modifier genes: Genes that alter the effect of other genes Describe genetic pathologic conditions and abnormal phenotypes Turner syndrome: XO Webbing of neck Short stature Coarctation of aorta Low hairline Klinefelter Syndrome: XXY Technically male Male with female physical characteristics Happens via nondisjunction Poly-X female: Tall and thin Learning development challenges Normal life span XYY males Tall  Y doesn’t have as much genetic info Lecture 17 - Chromosomal Variation Explain principles of gene linkage and separation and calculate probabilities of gene recombination and order Principle of segregation: Alleles separate during meiosis They separate independently And recombine to form recombinations Segregation is affected by gene proximity Closer the genes are, the more likely they are to be inherited together Linked genes = nonrecombinant progeny ○ Coupling/Cis configuration: Wild-type are both on same allele while both mutant genes are on the other ○ Repulsion/Trans configuration: One wild-type and one mutant gene on each chromosome Either configuration will affect the observed phenotypes Recombination frequency: Likelihood of two genes on a chromosome will undergo a cross over 0-50% Frequency = (# of recombinant progeny)/(total # of progeny) * 100 Used to make genetic maps 3 point testcross: technique used to determine gene order and location of crossovers and double,crossovers More efficient & accurate gene mapping technique Looking at the average amount of chromosome at a spot Calculate genetic interference and expound upon its significance Coefficient of coincidence (CoC): measures whether two crossovers are independent or one influenced the other Aka the degrees of interference Coc < 1 ○ Positive inference ○ Negative correlation  ○ 1st crossover reduces the likelihood of the second Coc = 1 ○ No correlation/influence Coc > 1 ○ Negative inference ○ Positive correlation ○ 1st crossover increases the likelihood of the second ○ The larger the Coc, the stronger the interference effect Coc = Observed double crossovers / Expected double crossovers ○ Expected double crossovers = (#singleAB * #singleBC * #singleAC) / (total #^2) Mapping Techniques Karyotyping: Arranging the chromosomes by size Cell must be actively dividing in metaphase Banding: Looking at the bands on the chromosomes G band: Chromosomes condensation, done with a giemsa stain Q band: Done with a quinacrine mustard C band: Centromeric heterochromatin/repetitive DNA R band: Area rich in C-G base pairs Describe the different types of chromosomal mutations and variations and explain their effects Variations Morphology: centromere position varies Chromosomal number: Mitotic nondisjunction leads to aneuploidy Mutations Aneuploidy: Altered number of an individual chromosome Types: ○ Nullisomy: 2n-2 ○ Monosomy: 2n-1 ○ Trisomy: 2n+1 ○ Tetrasomy: 2n+2 Caused by robertsonian translocation, deletion of centromere, or nondisjunction Notable aneuploidy: ○ Turner Syndrome (XO) ○ Klinefelter Syndrome (XXY) ○ Trisomy 21 (Downs syndrome) Polyploidy: One or more complete SETS of chromosomes (23 multiplies) Can be autopolyploidy (same species) or allopolyploidy (two species) Causes larger cell size and plant characteristics Chromosomal rearrangements **Any rearrangement can cause unbalanced gene products, congenital birth defects, or atypical development** Duplication ○ Leads to misalignment in meiosis and causes phenotypic changes Deletion ○ Causes pseudodominance ○ Causes Haploinsufficiency (one chromosome isn’t enough for normal gene product so there is an altered phenotypic expression) Inversion ○ Paracentric: does NOT involve centromere ○ Pericentric: does involve centromere ○ Only a problem in heterozygous individuals ○ Crazy looping has to occur to allow for pairing of chromosomes during prophase I Translocation ○ Reciprocal: Balance switch between two chromosomes  ○ Nonreciprocal: Unbalanced; Only one chromosome gains material ○ Robertsonian: Fusion of two acrocentric chromosomes into one large chromosome Notate robertsonian translocations: Pateau (13 & 13), Down (14 & 21), and Edward’s (18 & 18) Fragile Chromosome: specific sequences and genes are more likely to break off Seen in cancers Examples: Down Syndrome: incorrect number of 21’s Types: ○ Primary = caused by random disjunction Trisomy 21 ○ Familial = caused by robertsonian translocation between 14 & 21 Two 14’s but only 21 Lecture 18 - Population & Evolutionary Genetics I Describe, interpret, and apply principles of evolution Evolution: Fundamental concept of how species change and adapt over time Principles: Descent with modification: All living organisms have a common ancestor and species change over time Natural selection: Survival of the fittest (those better suited to the environment will survive and reproduce) Selective pressures: An external agent that affects the organism’s ability to survive in a given environment Positive pressures favor mutations Negative pressures do NOT favor mutation Selective pressures drive the process of natural selection Variation: There is genetic variation in a population which natural selection will act on Heritability: Traits favored by natural selection and are passed on to offspring Not encoded in DNA Adaptation: Population adapting better to their environments thanks to natural selection Leads to the development of new traits/refinement of existing ones Overproduction & Competition: Populations will produce more offspring than can be supported Fossil record: Fossils are real and the provide record of the history of life on Earth Homology: Structures with similar features shared by different species due to a common ancestor Biogeography: Species in different regions having similar adaptations to similar environments despite long standing separation Genetics: DNA sequencing shows genetic similarities between species indicating shared ancestry Explain the Hardy-Weinberg Law and use related principles to solve problems about population genetics and genetic/allelic frequency Population genetics: Study of genetic makeup and changes within populations Looks at the distribution and frequency of alleles in the population Genotypic Frequency f(AA) = # AA individuals / # population Allelic Frequency f(A) = # AA individuals and ½(# of Aa individuals) / # population Hardy-Weinberg equilibrium: the distribution of alleles and genotypes in a population over various generations when specific conditions are met Allelic and genotype frequencies will REMAIN CONSTANT between generations if the conditions are met Conditions: ○ Large population size ○ Random mating ○ No migration ○ No mutation ○ No selection (natural selection) 2 2 Equation: 𝑝 + 2𝑝𝑞 + 𝑞 = 1 2 ○ 𝑝 = 𝐴𝐴 2 ○ 𝑞 = 𝑎𝑎 **If given a %, take the square-root of that value to solve p/q** Describe and apply principles of mutations and gene flow in the context of evolutionary genetics Mutations introduce genetic variation and starts the process of evolution Rarely beneficially ○ Natural selection will preserve the goods and delete the bads one Source of new alleles, genetic variation, and diversity in a population Factors in mutations Genetic Drift: random changing of allele frequencies due to chance Can lead to fixation of some alleles and loss of others ○ Fixation leads to complete genetic uniformity (bad news) Speciation: forming of new species due to mutations Two species cannot successively reproduce Adaptive radiation: Single ancestral species diversifies into many species, each with an adaption to a specific ecological niche Darwin’s finches Evolutionary trade-offs: The benefit of an evolved trait comes at the expense of another Birds: You get wings but you lose your arms Coevolution: Mutation in one species can drive evolution in another species to make it better suited to the first species Gene Flow: Transfer of genes from one population to another WITHIN a species Done via migration or by dispersal of gametes ○ Dispersal of gametes: pollen or seeds released in the air Interrupting factors: ○ Barriers to gene flows: mountains, oceans, roads that limit gene flow Promotes genetic differentiation between populations and eventually speciation Homogenizing effect is seen in high gene flow cases (genetic makeup is homogenized between different populations) Conversation: maintain or preserving gene flow in fragmented population after something happened to affect it Preserve genetic diversity Lecture 19 - Population & Evolutionary Genetics II Explain principles evolution, including base and chromosomal mutations/abnormalities, genetic drift, and horizontal gene transfer Evolution = real fact (things change over) Abiogenesis = theory (how did life start from nonliving?) Evolution =/= Abiogenesis Molecular evolution -> Genetic variation -> Natural selection -> Evolution Molecular evolution happens at anticipated rates ○ Rate of nucleotide substitution The higher the rate of substitution, the less of effect the protein has ○ Molecular clock: rate at which protein evolves Genome evolution: changes that impact the entire chromosome Exon reshuffling for DNA recombination Gene duplication ○ Multigene family concept: genes share similarities in their nucleotide sequences AUG = start codon in almost every species Horizontal gene transfer: transferring genetic material to an organism that is not offspring ○ Mechanism: Transformation: getting DNA from environment Transduction: getting DNA from virus Conjugation: Bacteria getting genetic material from plasmid/sex pili Recurrent mutations: mutations that occur independently and repeatedly in a species Changes allelic frequencies Forward and reverse mutations maintain equilibrium Gene drift causes founder effect and genetic bottleneck Founder Effect: small group of individuals break off to establish new population Has reduced genetic diversity and different allele frequency than original population ○ Reduced genetic diversity -> increased risk of genetic disorders Key focus: small and isolated population Bottleneck Effect: Catastrophic event or sudden environment change dramatically reduced the population size  Leads to: ○ Founder’s effect ○ Inbreeding Inbreeding leads to reduced overall fitness ○ Reduced adaptive potential: with fewer individuals you may not have anyone with the trait to ensure survival ○ Genetic homogeneity Calculate fitness and selection coefficients for given genotypes Fitness: An individual’s ability to survive and reproduce “W” ○ W =1 (highest fitness) ○ W 0 Natural selection is an evolutionary force General selection model: Describes how natural selection acts on genetic variation Methods: ○ Genetic variation ○ Selective pressures ○ Fitness ○ Adaptation ○ Disruptive selection: Both extreme phenotypes (both homozygotes) have higher fitness ○ Directional selection: One type of extreme phenotype (homozygote) has higher fitness ○ Stabilizing selection: Intermediate phenotypes (heterozygotes) have higher fitness ○ Frequency-dependent selection: Fitness of a phenotype is dependent on its frequency Anagenesis: evolution taking place in a single group over time (straight line) Cladogenesis: splitting of one lineage into two, new species (fork in the road) Speciation happens through the evolution of reproductive isolation Mechanisms that prevent different species from interbreeding Processes: ○ Allopatric speciation: Geographic barrier splits the population into multiple isolated groups ○ Sympatric speciation: No geographical barrier, populations live together but don’t breed due to other reasons Phylogeny: Evolutionary relationship between a group of organisms Mapped out as a phylogenetic tree Lecture 20- Quantitative Genetics Explain and foundational concepts of quantitative genetics Quantitative genetics: Multiple genes and multiple environmental factors are influencing expression Vary continuously ○ Leads to range of phenotypic variation Applied in agriculture, animal breeding, and human genetic Key Concepts: Polygenic inheritance: controlled by multiple genes that can be additive or non-additive Heritability ○ Broad or narrow-sense Selective Response: Predict phenotypic change ○ Breeder’s equation Genetic and Environmental covariance: traits vary when including both genetics and environment Quantitative Trait Loci (QTL) Mapping - marking genes/regions that have quantitative traits ○ Height, weight, or blood pressure Phenotypic plasticity: Same genotype but different phenotypes in response to different environment Discontinuous (Qualitative): distinct phenotype Few, well defined phenotypes Continuous (Quantitative): spectrum, overlapping phenotypes Range of phenotype Quantitative Genetics: Phenotypes overlap **You cannot tell the genotype of phenotype since the AA, Aa, and aa phenotypes overlap** Quantitative Characteristics: Meristic: measured in whole numbers ○ Puppy litter size Threshold: may look like discontinuous/qualitative but technically a continuous/quantitative trait but it has to reach a threshold to become the second type of phenotype ○ Only two possible phenotypes: Present or absent Polygenic: STILL follows Mendel’s rule: dominant wins out but environment will have an effect on the gene  ○ Nilsson-Ehle experiment on corn kernel color Understand and apply basic genetic statistical methods and equations Statistics are required for analyzing quantitative characteristic Parametric: Specific assumption about data distribution Non-parametric: doesn’t make these assumption Normal Distribution = Gaussian distribution = Bell Curve: Continuous probably that is symmetrically 68-95-99.7% Rule: Empirical Rule = The percentage of data within 1/2/3 standard deviations ○ 1 SD= 68, 2 SD= 95, 3 SD = 99.7 Non-normal= Skewed: Indicates Bias Flaws in data collection leading to biases which lead to incorrect conclusions Frequency distribution = variance Mean: calculated average of dataset Center of a normal distribution Affected by large off-set outliers Median: The middle number in dataset ordered from least to greatest NOT affected by large outliers Mode: the number that appears most often in dataset Variance: the variability of a group of measurement Standard deviation asses variances (aka the square-root of variance) ○ SD increases with dataset variances Standard Deviation Calculations: 1. Calculate mean 2. Subtract mean from each data point 3. Square each results 4. Add them together 5. Divide by population OR sample size 6. Take square root of that Describe variance, heritability, and response to selection and use the Breeder’s equation and its various forms to solve genetics problems Variance: there’s a lot of factors affecting phenotypic variances Heritability Broad-sense: All sources of genetic variation (additive, dominance, interaction effects) ○ H = Genetic variance/total phenotypic variance Narrow-sense: Focuses on additive genetic variance ○ h = additive variance/total phenotypic variance **Note the small h for narrow-sense**  Limitation of heritability: ○ Doesn’t indicate degree (where it is on spectrum) ○ Only to population, not individuals ○ No universal heritability ○ Environment factors may influence characteristic ○ Not about population differences Selection of Variable traits: Artificial: We are selecting for a specific trait Natural: not controlled Response to selection: extent to which a characteristic subject to selection changes in one generation (aka how much the next generation will change) The Breeder’s Equation R = h^2 x S h^2 = narrow-sense (don’t actually square this value) ○ Ranges from 0-1 0: only environment influences 1: only genetics influences R = response to selection S= selection differentials = difference between the mean of the selected individuals and mean of entire population ○ how different a group is from the average population ○ S = xgroup - xpopulation Response selection levels off over time You can use breeder’s equation to solve for narrow-sense or selection differential by rearranging the equation Lecture 21- Genetic Pathologies Explain details of cancer pathogenesis Cancer= uncontrolled growth Not a specific disease Benign vs Malignant ○ Benign: non-cancerous tumor, don’t spread ○ Malignant: cancerous, DOES spread and establish new tumors elsewhere (metastasis) Aging and Cancer = mutations Environmental causes can cause cancer ○ Tobacco Biggest difference between men & women? Their prostate & breast (#1 prostate & breast cancer) You have 2 lungs (#2 lung cancer) Nevermind #2, you gotta go #3 (#3 colon & rectum) Bl4dder (#4 bladder & uterine) 5kin (#5 melanoma) Carcinogens: Anything that causes cancer Multisteps are needed for something to become cancer Normal cells evolve into malignant cells Tumor = clone of one cell Germline : passed down mutations Some cancers predecessors can be inherited (putting you at risk for it) Somatic Mutations: picked-up mutations Acquired mutations Define and describe systemic pathologies and their genetic associations Mutation in multiple genes will cause cancer Oncogenes: mutated genes that CAUSES cancer Proto-oncogenes: normal cell that can when mutated becomes an oncogene Only 1 copy to mutate to get cancer Tumor-suppressor gene: Should inhibits uncontrolled proliferation of cells, repair of damage DNA Both tumor suppressor genes need to be mutated to be cancerous BRCA1: “bra” -> breast cancer CDKN2A: cdkn =“skin” -> melanoma NF1= NeuroFibromatosis P53: you’ll get 53 types of cancer RB = Retinoblastoma P53 = “guardian of genome” Integral to so much of cell function that it translates into many types of cancer Telomerase: enzyme that prevent telomere shortening In cancer they upregulate telomerase expression making the cancer immortal Epigenetics: Study in heritable traits that do not involve DNA sequence alterations How genes are expressed or regulated Everything around the gene that changes how the gene interacts Associated with cancer (not actually cancer though) NOT mutations since they are reversible (able to be turned on/off) Changes in chromosome number and structure = cancer Viruses can cause cancer HPV-16 & HPV-18 HPV is retro virus ○ Retrovirus can mutate proto-oncogenes into oncogenes Leukemia: Blood & bone marrow cancer Chronic myeloid leukemia ○ Philadelphia chromosome: region on chromosome ○ Reciprocal translocation 9 & 22 ○ BCR-ABL1: gene Inhibits WBSC apoptosis -> many too WBC Burkett Lymphoma ○ Reciprocal translocation 8 & 14 ○ Involves B lymphocyte Non Hodgkin's lymphoma ○ Associated with Epstein-barr virus ○ Involves the jaw Cystic Fibrosis: sticky mucus buildup in airways CFTR gene Autosomal recessive Sickle Cell Disease HBB gene -> HbAs (mutated gene) Chromosome 11 Hemophilia Clotting Factor VIII with F8 gene X related Huntington’s Disease HTT gene Muscular Dystrophy DMD gene Fragile X syndrome FMR1 gene on x chromosome Leads to intellectual disability, autism spectrum disorder Define and describe ocular pathologies, their genetic associations, and genetic counseling RB: Retinoblastoma mutated gene G1/S checkpoint RB binds to E2f E-CDK/D-CDK bind to RB making it let go E2F so E2F goes and stimulations DNA replication *MUTATION: RB nevers with E2F so replication always happening** Down Syndrome: Trisomy 21 Congenital cataracts Marfan Syndrome FBNR 1 gene Subluxated lenses Retinitis Pigmentosa (RP) Clinical triad: arteriolar attenuation, bone spicules, waxy disc pallor Progressing vision loss leading to total blindness Genes: ○ Rho ○ RP1, RP2, RPGR ○ PRPF Glaucoma Genes: ○ MYOC ○ OPTIN ○ CDKN2B-AS1 AMD Complement genes on chromosome 1 ARMS2/HTRA on chromosome 10 Congenital Cataract Downs Albinism  Lack of pigmentation of iris and retina Corneal dystrophy Defects in cornea Genetic Counseling Be nice to them, don’t tell them what they can do Lecture 22- Basic Principles of Nutrition Describe the basic principles of human nutrition Macronutrient: carbs, lipids, and proteins Carbs= 4 cal/gram= grains Proteins= 4 cal/gram meat Lipid= 9 cal/gram: dairy Micro: mineral & vitamin Balanced diet is important More veggies, less dairy Portion control important BMR= Basal metabolic rate How old and how active determine baseline of metabolism/calories needed Sedentary Mod active active * Male’s caloric needs start where female’s ends M 19-30: 2500 / 2700/ 3000 M 31-50: 2300/ 2500/ 2900 F : 1900 / 2100/ 2400 F : 1800/ 2000/ 2200 Younger Guys will say they’re 25, 27, or 30 years old Older Guys wish they were 23, 25, 29 years old Younger Women will say they’re 19, 21, or 24 Older Women wish they were 18, 20, 22 1lb fat = 3500 calories Wasting fuel = thermogenesis Fat Saturated fats ○ S for single bond ○ Moderately bad ○ Raises LDL Unsaturated (cis) fats ○ Double bonds ○ Most healthy ○ Omega 3 & 6 fats = inflammation regulation ○ Double Bond shape: Trans fat ○ Trans double bond fat ○ Worst of fats ○ Hydrogenation ○ Raises LDL and lower HDL ○ Double Bond shape: Hydration: Drink half of body weight in oz daily Limit salt & sugar Salt: water retention -> increase blood pressure ○ Diuretics help you pee out the fluid Sugar: stores more fat ○ Overall just a bad time Fiber Non Digestible carbs Helps keep you regular Lowers risk of colon cancer and GI issues  Makes you feel full = satiety Slows down absorption of sugar ○ Increases insulin sensitivity Good for cholesterol & blood pressures ○ Lowers TAG, LDL, and blood pressures Be active, eat healthy, and keep learning Everyone has their own health needs because of age, health, genetics Explain and calculate Body Mass Index (BMI) Lb * 0.454 = Kg Ft * 0.305 = m BMI = kg/(m^2) **SQUARE the meters** 30 = obese >40 = severe obesity Gotta interpret BMI correctly Muscle weighs more than fat USA ~42% obese Correlates with education and ethnicity Obesity leads to pathology Weight loss = do what works for you Be healthy Anorexia Nervosa: Restricted eating with distorted body image Bulimia Nervosa: Binge eating and vomiting Describe consequences of poor nutrition It affects everything Vision problems Gotta get minerals and vitamins for eye health DM2  Insulin resistance Metabolic syndrome: 3 of 5 ○ Abdominal obesity ○ High BP ○ DM ○ High serum TAGs ○ Low serum HDL Malnutrition: not having food, not digesting food Weight gain & obesity Underweight Heart issues Osteoporosis Dental problems Anemia Impaired immune function Mental health Lecture 23- Digestion Describe the digestion of proteins Mouth: Mechanical breakdown happens in mouth Stomach: Gastric juices released HCL + pepsinogen = pepsin HCL & pepsin breakdown/denature proteins into peptide bonds Chyme (partially digested food) moves to small intestine Small Intestine: Main absorption area Pancreatic juices break down peptide bonds into small peptides ○ Trypsin ○ Chymotrypsin ○ Carboxypeptidase Brush Border enzymes break peptides into AA AAs absorbed by enterocytes and taken to bloodstream Bloodstream: AA go all through body as needed for protein synthesis Extra AAs are taken to liver ○ Amine removed from AA structure Urea Cycle (Amine = ammonia -> urea)  Urea sent to kidney for removal via urine Chyme moves to colon Colon NO more absorption of peptides Fermentation by gut microbiota ○ Byproduct: gas (methane, CO2) Reabsorption of water ○ AA may be absorbed as well Fecal matter formed Proton Pump Inhibitors (PPI): medication that reduces stomach acid production Inhibits Na-K proton pump -> no secretion of gastric acid Treats excess stomach conditions Suffix “-azole” Side effects: Increased risk of fractures,kidney disease, and nutrient deficiencies ○ If you aren’t breaking down the food, you can’t absorb the nutrients! Describe the digestion of carbohydrate Types of carbs: Monosaccharides: Glucose, fructose, galactose Disaccharides: Maltose, Sucrose, Lactose Polysaccharides: Complex carbs (Starch & fibers) Mouth: Amylase secreted by salivary glands Carb digestion begins in the mouth Stomach: Gastric acids denature amylase Food made into chyme Small intestine: Main site of carb digestion Chyme triggers secretin & cholecystokinin -> trigger pancreatic amylase Pancreatic amylase breaks starches -> disaccharides Maltase, Sucrase, and Lactase break disaccharides -> monosaccharides ○ Same name as the 3 types of disaccharides Monosaccharides get absorbed into bloodstream Bloodstream: Fructose & galactose go to liver to become glucose Glucose goes to cells Colon: Undigested carbs = fiber Some fiber gets fermented making short chain FA ○ Some FAs are absorbed Majority of fecal matter = indigestible carbs Fiber is good for colon health Insulin & Glucagon: High blood sugar: Pancreas uses GLUT2 receptor to monitor blood glucose levels ○ High levels = release insulin into bloodstream via pancreatic beta cells Insulin binds on insulin receptors on cell surface ○ GLUT4 comes from inside the cell to bring glucose into the cell Blood sugar level drops back down Extra glucose goes to liver or muscle tissue to get turned into glycogen Low blood sugar: Low levels = release glucagon via pancreatic alpha cells Glucagon triggers glycogenolysis ○ Glycogen broken down into glucose ○ Glycogenolysis = lysis of glycogen Lactose intolerance = You don’t have Lactase to break down Lactose so you take Lactaid Lactose = carb ○ Undigested carbs get fermented in colon ○ Fermentation causes gas ○ Gas = pain, bloating Lactase production decreases with age Biochem info Important for metabolic pathways ○ Glycolysis ○ MPC Complex ○ Kreb Cycle Generates NADH & FADH Vitamin B3 & B2 1 glucose = 30-32 ATP Describe the digestion of lipid Mouth: Lingual lipase secreted by salivary glands Stomach: Gastric lipase gets the lipid breakdown going Mechanical churning breaks food into fat globules as part of chyme Chyme moves to small intestine Small Intestine: Major site of lipid absorption Bile from liver and pancreatic enzymes released Bile causes the emulsification of fat globules into smaller droplets ○ Allows high enzyme action Pancreatic enzymes: ○ Pancreatic lipase: emulsified fats -> FAs and glycerol ○ Colipase: helps pancreatic lipase ○ Phospholipase: Phospholipids -> FAs and phosphates Micelles form from FAs and monoglycerides Enterocytes absorb FAs and monoglycerides ○ FAs & monoglycerides turn back into Chylomicrons Chylomicrons = Triglycerides = TAGs Lymphatic system: Chylomicrons too big for bloodstream so they go into the lymphatic system ○ Enter via Lacteals Chylomicrons can then enter the bloodstream via the lymphatic system Bloodstream: Lipoprotein Lipase breaks down chylomicrons so FAs can enter cells ○ Done via receptor-mediated endocytosis Leftover chylomicron gets sent to liver ○ VLDL: takes TAGs to cells ○ LDL: takes cholesterol to cells Boo! Bad ○ HDL: takes extra cholesterol from cells to liver Yay! Good Extra lipids stored in adipose tissue or excreted in feces Biochem info: Glycerol enters Glycolysis FFAs enter the cell FFA + Acetyl-CoA = Fatty acyl-Coa ○ Uses carnitine shuttle to get into mitochondria  Beta oxidation turns fatty-acyl CoA into Acetyl-CoA Acetyl-CoA goes into Kreb Cycle 1 palmitoyl-CoA = 108 ATP Lecture 24- Oxidative Stress, Vitamins, and Mineral Describe oxidative stress and ways to combat it Oxidative stress: imbalance of ROS and antioxidants ROS = free radicals and non-radial species ○ Non-radial: highly reactive ○ free radial: have the 1 free electron Causes: ○ Mitochondrial respiration ○ Inflammation Feedback Loop forms between inflammation and oxidative stress ○ Environmental factors Consequences: ○ Cellular damage/dysfunction ○ Inflammation ○ Pathology (cancer, aging, neurodegenerative diseases) Antioxidant: Neutralizing agents for ROS Can accept the free electron from the free radicals Can endogenous (produced by body) or exogenous (from diet) Examples: ○ Vitamin C: regenerate other antioxidants ○ Vitamin E: Protect cell membranes ○ Selenium: Synthesis of antioxidant enzymes ○ Glutathione: Tripeptide **Endogenous** ○ Carotenoids: Converts to vitamin A Combat ROS Antioxidative rich diets Avoid toxins Get enough sleep Exercise Oxygen Toxicity Excessive concentration of oxygen  Examples: Medical treatment, deep-sea diving, and prolonged mechanical ventilation Causes ROS and tissue damage Ways to control oxidative stress SOD = Superoxide dismutase Turns superoxide radicals into hydrogen peroxide Catalase Hydrogen peroxide into water and oxygen Glutathione Peroxidase Neutralize hydrogen peroxide and lipid peroxides Non-enzymatic antioxidants Vitamin C & E: directly scavenge free radicals ○ C(s)earch & Eat free radicals Glutathione: regenerates vitamin C & E Selenium: cofactor for glutathione peroxidase Metal-binding proteins: binds metals, prevents them from making ROS Blood Polyphenols: plant compounds Flavonoids Endogenous defense mechanism: cell have built in repair mechanism Healthy lifestyle: helps control oxidative stress Elaborate on the role of minerals in nutrition Vitamins + Mineral = essential nutrients Vitamins = organic ○ Covalent bonds, found in living organisms Minerals = inorganic, ingested via diet ○ No C-H bonds, nonliving materials Macro & microminerals needed for proper fluid balance, nerve function, and structure components Macro needed in large amount Micro needed in smaller amounts Macrominerals: Calcium, phosphorus, magnesium, sodium, potassium, chloride, and sulfur Chemical gates, neurotransmitters and synapses Microminerals: Iron, copper, zinc, selenium, manganese, iodine, fluoride  Less used so less needed Minerals functions Structural components:Calcium & Phosphorus: ○ Bones & teeth Electrolyte balance: Sodium, potassium, and chloride ○ Nerve function, NT, and muscle contraction Blood pressure: Sodium & potassium ○ High potassium makes the adrenal glands secrete aldosterone leading to higher blood pressure and sodium leads to water retention and absorption Cellular Function: Minerals are Cofactors for enzymes ○ Magnesium Oxygen transport: Iron ○ Example of metal-binding proteins Energy metabolism: Magnesium & zinc Antioxidant defense: Selenium and copper Thyroid function: Iodine Immune: Zinc and copper ○ Copper makes oxidative burst ○ Zinc makes T cell development Wound healing: Zinc Collagen synthesis: copper Blood clotting: Calcium and vitamin K Acid-base balance: Phosphorous ○ Phosphorus buffer system Nerve Function: Magnesium Fluid balance: potassium and sodium Cell growth & repair: zinc ○ Zinc is a cofactor for DNA synthesis Prevention of anemia: iron Detoxification: selenium Function sorted by mineral: Zinc: Energy metabolism Immune= T cell development Wound healing Cofactor for DNA synthesis Selenium: Antioxidant defense Detox Potassium: Electrolyte balance Blood pressure = secretion of aldosterone Fluid balance Magnesium: Energy metabolism Nerve function Cofactor for cellular function Calcium: Structure Blood clotting Copper Immune= Oxidative burst Collagen synthesis Sodium: Electrolyte balance Blood pressure = water retention Fluid balance Explain classifications and functions of vitamins Solute: particle Solvent: Just liquid Solution: (dissolved) Particle in liquid 2 categories: Water-soluble ○ Regular intake is necessary ○ Dissolves in water ○ Excreted in urine ○ 9 Vitamins B1-12 **Not include B4, B8, B10, and B11** C  Fat soluble ○ 4 vitamins KADE ○ Stored in fatty tissues ○ Not easily excreted Vitamin A Synthesis of retina ○ Rhodopsin turns 11-cis-retinal is changed to 11-trans-retinal with the help of cofactor Deficiencies: night blindness and visual impairment Excessive amounts is toxic Important for immune function and skin health **Mnemonic: The Really Nice Panda Provides Bamboo For Children** Vitamin: 1, 2, 3, 5, 6, 7, 9, 12 Vitamin B1 - Thiamine Necessary for metabolism Important cofactor for metabolic pathways ○ Pyruvate dehydrogenase ○ Alpha-ketoglutarate dehydrogenase ○ Transketolase Important for nerve and heart Vitamin B2 - Riboflavin Forms coenzymes FMN & FAD ○ FAD needed to make glutathione ○ Electron carriers Used in corneal crosslinking Vitamin B3 - Niacin Used for Metabolism Makes NAD ○ Electron carrier Deficiency: Pellagra ○ Diarrhea ○ Sun-sensitive dermatitis ○ Inflammation of mouth & tongue Vitamin B5 - Pantothenic Acid Synthesizes CoA Vitamin B6 - Pyridoxine Cofactor for AA metabolism Deficiency: rash and inflammation around eyes and mouth, peripheral neuropathy Vitamin B7 - Biotin Metabolism and gene expression Binds tightly streptavidin Vitamin B9 - Folate Crucial for fetal development Necessary for DNA & RNA synthesis and RBC formation **B9 = 9 months of pregnancy** Vitamin B12 - Cobalamin Essential for nerve function and DNA synthesis and RBC formation Vitamin C Antioxidant Immune function Collagen synthesis Deficiency: Scurvy Vitamin D UVB converts 7-dehydrocholesterol into vitamin D3 in the skin Obtained from diet Essential for calcium and phosphorus absorption and mood regulation Deficiency: ricketts Vitamin E Antioxidant Protects cell membranes Affects gene expression and regulate PKC ○ Protein kinase C Vitamin K  Essential for blood clotting ○ Uses calcium Supports bone health and heart health **K for klotting** Vitamin F - Essential Fatty Acids Alpha-linolenic acid (ALA) & Linolenic acid (LA) ○ Omega acids Important for cell membrane structure, brain function, and inflammation regulation Good luck everyone!