Protein, FN 1070, Week 8, Chapter 6 PDF

z PROTEIN FN 1070 – Week 8 (Chapter 6)  z THE CHEMISTRY OF PROTEINS AND AMINO ACIDS (AA) § Proteins § Comprised of 20 different amino acids § Amino Acids § Made up of C, H, O and N atoms § Amino group (NH2), acid group (COOH), Hydrogen and unique side ch...

z PROTEIN FN 1070 – Week 8 (Chapter 6)  z THE CHEMISTRY OF PROTEINS AND AMINO ACIDS (AA) § Proteins § Comprised of 20 different amino acids § Amino Acids § Made up of C, H, O and N atoms § Amino group (NH2), acid group (COOH), Hydrogen and unique side chain § Side chain § creates a unique chemical structure § differentiates one AA from another § makes AA differ in size/shape/electrical charge  z AMINO ACIDS § Amino acids join together via peptide bonds to form proteins in the body § Peptide bond: chemical bond formed between the amine group end of one AA and the acid group end of the next § Electrical charge § Each AA carries an electrical charge that attracts or repels various ends of each AA resulting in different shapes (e.g., globular, strips, coiled, etc.) and sizes § Shape of an AA § Enable them to perform different tasks § Examples: § Enzymes act as protein catalysts § Globular hemoglobin carries O2 & Fe § Collagen makes up tendons and ligaments z DISPENSABLE/NON-ESSENTIAL AMINO ACIDS § Non-essential: the body can synthesize these § Dispensable AA: § Alanine § Asparagine § Aspartic acid § Glutamic acid § Serine  z INDISPENSABLE/ESSENTIAL AMINO ACIDS (EAA) § Cannot be synthesized at all or are present in insufficient amounts to meet physiologic needs § Must be supplied by the diet § Nine Essential AA: Histidine Phenylalanine Isoleucine Threonine Leucine Tryptophan Lysine Valine Methionine  z CONDITIONALLY ESSENTIAL AMINO ACIDS § Normally non-essential AA, but must be supplied by the diet when the body cannot meet its needs § E.g. Tyrosine from phenylalanine becomes essential in phenylketonuria (PKU) § Conditionally Essential AA: § Arginine § Cysteine § Glutamine § Glycine § Proline § Tyrosine  z PROTEIN § Made up of linked amino acids in a variety of sequences AMINO ACID CHAINS § AA connected by peptide bond § Formed by condensation reactions § Dipeptide (2 AA bonded together) § Tripeptide (3 AA bonded together) § Polypeptide § Consist of a few dozen to several hundred AA  z STRUCTURES: § Primary structure (sequence): § Sequence of AA varies among different proteins § Secondary structure (shape): § Determined by weak electrical attractions within the polypeptide chain § Attraction between H(+) and O (-) cause the structure to twist § Provides strength and rigidity to the protein  z STRUCTURES: § Tertiary structure (tangle): § Unique side chains either repels/attracts other AA or fluids § Hydrophilic – attract water, on outer side near water § Hydrophobic – repel water, tucked on inner side of polypeptide § Variety of shapes/structures allow them to do various tasks within the body § Globular, linear § Final shape the protein assumes needs to be maintained to remain functional § Quaternary structure (interactions among polypeptides): § Some polypeptides must interact with others to become functional § E.g. Hemoglobin § Four polypeptide chains each holding Fe z DIGESTION & ABSORPTION  z Denaturation of Proteins § Irreversible change in protein’s shape due to heat/acids/bases/alcohols/salts of heavy metals (Hg, silver) § Shape uncoils resulting in a decrease in ability for the protein to maintain its usual function § Useful in cooking - heat denatures protein in raw egg (egg white hardens) § Stomach acid denatures proteins in the body, allowing them to become digested  z Protein Digestion § Mouth § No digestion; simply breaking down of food into small pieces by chewing § Saliva moistens food to prep for swallowing § Stomach § HCl denatures protein allowing for enzymes to break peptide bonds § HCl converts pepsinogen (inactive form) to pepsin (active form) § Pepsin breaks apart AA strands into polypeptides & some single AA § Secretion of mucous for protection from acidic environment § Note: no food can make the stomach acid more acidic as it is at a pH of 1.5 already  z Protein Digestion § The Small Intestine & Pancreas: § Alkaline (basic) pancreatic juices § neutralize the acidic solution § liquids pH rises to 7 (neutral) § Proteases from pancreas & intestine § split peptide strands into tri- and dipeptides & AA § Peptidase enzymes on surface & within cells of SI § split tri- and dipeptides further into AA § Intestinal cells move AA to bloodstream à transported to liver à used and distribution to body cells  z Protein Absorption & Synthesis: § Intestinal cells § Transported into cells via carriers § Used to synthesize compounds or for energy § Capillaries à Liver § If not used in the cell, transported across cell membrane into fluid entering the capillaries and go to the liver § Enzymes: § Function optimally in certain pH § Outside of this pH – denatured and digested § E.g. Pepsin § Works well in stomach § Becomes denatured when reaches higher pH of small intestine z Protein in the Body  z ROLE OF PROTEIN IN THE BODY § Proteome: more than 1 million kind of proteins in the body (only a few thousand have been studied well) § Each protein has a standard AA sequence specified by heredity § Each protein has a specific function, determined during protein synthesis § Any variation in the sequence can create life altering circumstances § Examples: § Sickle-cell anemia  z Protein Synthesis § Depends on a diet that provides adequate protein and essential AA v DNA – serves as the template to make the mRNA (messenger RNA) v mRNA – carries message to body of the cell and has the instructions to make the needed proteins v Ribosomes – protein-making machinery of the cell v tRNA – collects AA from body pool/cell fluid & brings them to the mRNA  STEP 1: Transcription DNA strand is used as a template to make RNA (messenger RNA) mRNA carries the code into the body of the cell Attaches itself to a ribosome STEP 2: Translation RNA determines the sequence the AA line up in to form a protein  z Lining up Amino Acids: § tRNA (transfer RNA) § Collect amino acids from surrounding fluid § Each AA has it’s own transfer RNA § Cluster around the ribosome § Messenger calls for each AA in sequence, it is delivered by transfer RNA – this is based on the code that was initially transcribed § Complete proteins are then released  z Sequencing Errors § Result in altered proteins either from: § Genetic error altering the AA sequence of the protein or § Error copying the sequence § Sickle Cell Anemia § The protein Hemoglobin (Hgb) is abnormal § 2 of the 4 peptide chains have normal AA sequencing, but the other 2 do not § Valine is present instead of glutamic acid § Unable to effectively carry oxygen due to shape alterations (disk shape collapses into crescent shape) § Complications: § Increased energy needs § Abnormal blood clotting § Prone to dehydration § Can be fatal  z Roles of Protein 1. Building Materials for Growth & Maintenance § Build new tissues (blood, muscle, scar tissue, hair, nails, skin, RBC, intestinal lining, etc.) § Replace dead/damaged cells § Collagen § Used first in the formation of bone followed by the addition of Ca, P, fluoride and other minerals § Materials needed for ligaments and tendons § Strengthens the arterial walls to withstand pressure from blood passing through  z Roles of Protein 2. As Hormones: § Messenger molecules § Some hormones are proteins § Released in response to stimuli – travel in the blood to target tissue § Elicit response at target tissue to maintain normal conditions Insulin and glucagon à blood glucose control Antidiuretic hormone à regulates fluid and electrolyte balance Thyroxine from tyrosine à regulates BMR  z Roles of Protein 3. As enzymes: § Can break down substances, build substances and transform substances § Catabolic (to break down), Anabolic (to build-up) § Enzymes as protein catalysts – they themselves remain unchanged 4. As Acid-Base Regulators: § Accept and release H ions to maintain acid-base balance of blood and body fluids § Goal is to avoid acidosis or alkalosis, as these would denature proteins, disruption proper body functions  z Roles of Protein 5. As Regulators of Fluid Balance: § Proteins usually within the cells and in plasma § During critical illness or protein malnutrition: § Proteins leak into tissues between cells § Protein attracts water, therefore, causing swelling (edema) § Causes of edema related to protein: § Excessive protein loss (critical illness, inflammation) § Inadequate protein synthesis (liver disease) § Inadequate dietary intake § Results in a reduced ability of cells to function as they are not able to receive adequate nutrients/oxygen or remove waste  z Roles of Protein 6. As Transporters: § Carry nutrients in the body fluids § Hemoglobin – carries oxygen from lungs to cells § Lipoproteins – carry lipids around the body § Fe may move from various proteins to execute it’s role in the body (transport protein through the blood to cell, storage protein in the cell etc.) § May act as pumps § Pick up a compound on one side of the cell and release on the other side § E.g. movement of Na and K in and out of cells to maintain appropriate balance for normal bodily function z Roles of Protein 7. As Antibodies § Antibodies – giant protein molecules § Designed to destroy specific invaders (bacteria, virus, toxin, allergen) § Body develops immunity to the invader § Each antigen has a specific antibody § Molecular memory underlies principles of immunizations (lifelong, boosters) z Roles of Protein 8. As a Source of Energy and Glucose § Sacrificed in times of starvation or inadequate carbohydrate or total energy intake § Breakdown of tissue proteins to free AA to be used as energy or make glucose (Gluconeogenesis) § Not ideal, consequence is loss of lean body mass § Goal is to spare protein from being used Other Roles: § Blood clotting and vision z Protein Metabolism z Protein Turnover: § Occurs within each cell § Proteins are continuously being made and broken down § Amino acid pool § Pattern of AA remains fairly constant despite varying rates of protein degradation and protein intake § AA not stored for later use 1. Used to make body proteins or other N containing compounds OR 2. N is removed, resulting in a carbon backbone to be used for energy now or stored as fat for later z Nitrogen Balance: § Healthy individuals – usually in a state of Nitrogen Equilibrium § Protein synthesis = protein degradation § Protein intake = protein excretion § Positive Nitrogen Balance – growing children, pregnancy, person building muscle § Negative Nitrogen Balance – surgery, infection, starvation z Using Amino Acids to Make Other Compounds: § AA Tyrosine à norepinephrine and epinephrine (neurotransmitters) § AA Tyrosine à pigment melanin (hair, eye, skin colour) § AA Tyrosine à hormone thyroxin (regular BMR) § AA Tryptophan à precursor for niacin (vitamin) § AA Tryptophan à precursor for serotonin (neurotransmitter – sleep, appetite, sensory perception) z Using Amino Acids to Make Fat § Energy and protein intake exceed needs, adequate CHO intake § Abundant protein à shift of energy metabolism to use more protein than fat § Excess AA converted to fat to be stored § Protein rich foods, excess in energy compared to the body’s needs à weight gain z Deaminating Amino Acids § Deamination – when amino acids are stripped of their N- containing amino group during protein breakdown § Produce: § Ammonia (NH3) § Keto acid § Used for energy to produce glucose, ketones, cholesterol, fat § Used as carbon skeletons to produce dispensable/nonessential AA z Using AA to Make Proteins and Non- Essential AA § Body will break down available proteins to make missing essential AA § Making non-essential AA from Keto acids § Transamination § Transfer of amino group from one AA to its corresponding keto acid § Liver can synthesize non-essential AA through many transamination reactions and keto acids  z Converting Ammonia to Urea § Ammonia § Toxic compound § Excess amounts can disrupt acid-base balance § Ammonia + CO2 = urea § Produced by the liver § dietary protein intake = urea production § Max production rate with protein intake of ~250g/day  z Excreting Urea Ammonia + CO2 = Urea Filtered out Circulates of the blood Liver Urea Blood until reaches Kidneys Excreted in released the kidneys the urine into the blood Failure of these systems leads to kidney and liver disease: Kidney disease = urea in blood Liver disease = ammonia in blood Urea is used to excrete excess N Need adequate water intake to keep urea in solution in order to properly excrete excess urea High protein diet without adequate water can pose risk of dehydration z Protein In Food: Quality, Use & Need  z Protein Quality: § High-quality Protein § Contains all EAA § May also contain non-EAA § Quality is influenced by the proteins digestibility and AA composition § Generally derived from animal products (meat, fish, poultry, cheese, eggs, yogurt, milk) § Soy protein § Low-quality protein § Does not contain all EAA § Cannot support protein synthesis alone § E.g: Corn protein § Proteins derived from plants § Diverse AA patterns, tend to lack one or more EAA  z Complimentary Proteins § Can improve quality of plant proteins by combining different foods to obtain all EAA § Combine foods at each meal vs the day? § Limiting AA z Protein Complementation ASN staff. Protein Complementation. American Society for Nutrition. March 2011. https://nutrition.org/protein-complementation/  z Protein Quality & Digestibility § Digestibility depends on: § Source of the protein § Other foods consumed with the protein Measuring Protein Quality: § Protein digestibility–corrected amino acid score (PDCAAS) § Determines protein quality § Reflects protein’s digestibility § Reflects the proportion of AAs it provides § 100 - Egg white, ground beef, chicken, fat-free milk, tuna fish § 94 – soybean protein, 50-60 – most legumes § AA from animal PRO most easily digested & absorbed (90%); legumes (80-90%); grains & other foods (70-90%) § Cooking with moist heat improves digestibility; while dry heat impairs digestibility z Food Labels: Protein § Must state the quantity of protein (grams) § May also have Nutrient Function or Nutrient Content claims § Using the PDCAAS when choosing products: § Canada – does not have a %DV on food labels for protein § U.S – has %DV § Manufacturers must use the PDCAAS to determine quality therefore; § Reflects digestibility and AA composition of foods z Health Effects of Protein  z Health Effects of Protein § Heart Disease § High intake of animal protein (containing SFA) can increase risk of HD § Replacing animal proteins with plant-proteins can reduce risk § Cancer § Protein itself does not increase risk, however, some protein rich foods may, while some may reduce risk § Processed meats vs legumes/fish § Osteoporosis (adult bone loss) § Increase protein intake, increases calcium excretion § Consider excess protein vs inadequate Ca  z Health Effects of Protein § Weight Control § Diet high in protein + fibre can reduce food intake, body wt and body fat § High protein diet + physical activity (resistance training) can help to preserve muscle mass and improve strength § Satiety: include a source of protein at each meal to reduce over-eating § Kidney Disease § Increased protein intake, increases work of the kidneys to excrete the end products of protein metabolism § Individuals with kidney disease may have to adjust their intake depending on the stage of the disease  z Protein Deficiency § Inadequate protein intake § Lacks intake of essential amino acids § Results in: § Slowed growth § Impaired brain and kidney function § Weakened immunity § Inadequate nutrient absorption § Protein-energy malnutrition § Inadequate protein and/or energy  z Protein-Energy Malnutrition (PEM) § Most widespread form of malnutrition in the world, due to starvation & hunger § Kwashiorkor (PRO deficiency) § Edema of belly & lower extremities § Skin rashes § May result from severe acute malnutrition of too little protein Marasmus Energy deficiency Affects Skin & bones Shriveled & lean all over Chronic inadequate food intake (inadequate energy, vitamins, minerals, & PRO) Marasmic-Kwashiorkor – combined symptoms Prevalent in Africa, Central America, South America, Middle East, East & South East Asia z Kwashiokor Child is weaned & fed watery cereal with scant PRO of low- quality Affects children 1-3 y.o.; no severe wasting of fat PRO & hormones diminished; fluid leaks out to belly & legs, causing edema Belly bulges with fatty liver (no protein carriers to transport fat out of the liver) Child’s hair loses color without sufficient tyrosine to make melanin; skin patchy & scaly; sores fail to heal  z Marasmus Commonly occurs in children 6-18 months old Muscles, including heart muscles, waste & weaken Brain development stunted; learning impaired Metabolism slowed; body temp subnormal Little or no fat to insulate against cold Engage in as little activity as possible, not even crying for food Skin loses elasticity, moisture; cracks and is difficult to heal Digestive enzymes in short supply; GIT lining Blood PRO (e.g., Hgb) not produced; anemic & weak High prevalence of infections due to weakened immune response Point of no return – body machinery for PRO synthesis has been degraded; heart failure & sudden death (from diarrhea, electrolyte imbalances, anemia, fever, infection) z Protein Recommendations  z Recommendations for Healthy Adults DRI: 0.8 g/kg BW/d for adults Slightly higher for infants and children Some research supports increased amounts for older adults (1.2g/kg/d) AMDR: 10-35% of total calories from PRO DRI recommendations assume a “normal mixed” diet with a variety of protein sources, and are for healthy individuals Canada’s Food Guide: Choose lean meats and poultry and prepare with little added fat Choose beans, peas, lentils, nuts, seeds etc. more often Choose unsweetened, lower fat dairy product WHO: 10-15% of total Kcal z Applying Recommendations: § Variety and moderation § 28g (1oz) provides ~7g of protein § Animal sources of protein: § Choose lean cuts of meat and poultry § Trim visible fat § Drain fat after cooking § Remove the skin § Include plant sources of protein § Dairy products § 1C of milk provides ~8g protein § Fruits, Vegetables & Grains § Vegetables and grains provide small amount of protein per serving (~2-3g) z Protein & Amino Acid Supplements z Protein Intake and Muscle Growth Can eating more protein make muscles grow bigger? § NO, excess protein deposited as fat § Food protein is generally enough § Generally no need for protein supplements/shakes § Muscle growth comes from: § physical training - triggers genes to build more muscle tissue § adequate energy & nutrients § good quality protein to support muscle growth § Post work out snack (within 15 minutes) § 3:1 ratio of quick carbs to protein § Gold standard: 1-2 cups chocolate milk  z Protein Powders § Used before/after exercise § Convenient, measured quantities § Whey protein § Contain an array of EAA § High leucine content § Rapid digestibility § Consumed after strength training can stimulate protein synthesis § Muscles and tissues can also be rebuilt/repaired by obtaining balanced meals  z Amino Acid Supplements § Regulated as Natural Health Products § Single AA do not naturally occur in food § Taken in high amounts can have negative impacts § Large doses can cause diarrhea § May cause deficiency of other AA § Diet can provide adequate amounts § Branched-chain Amino Acids § Support protein synthesis § Decrease muscle soreness § Taken right after resistance training § Relatively safe, but unnecessary § Lysine and Tryptophan z Vegetarian Diets  z Types of Vegetarianism § Vegetarian (exclude some/all animal derived products) § Partial vegetarian (allow most foods except some meats) § Pesco-vegetarian (Pesco = fish, also includes dairy and eggs) § Lacto-ovo-vegetarian § Lacto-vegetarian (Lacto = dairy) § Ovo-vegetarian (Ovo = eggs) § Vegan: Exclude all animal derived products § Fruitarian: Only raw or dried fruit/seeds/nuts – very low in nutrition  z Factors in the Choice to Become Vegetarian § Health concerns Heart health, weight, cancer, etc. § Environment concerns Large use of resources in production § Animal cruelty § Personal belief that humans are not meant to consume animal products Including meats, poultry, milk, eggs, honey, etc.) § Fear of food poisoning or “mad cow disease” z Positive Health Aspects of Vegetarianism § In general, vegetarians maintain a healthier body weight than non- vegetarians § Possibly due to increased fibre and decreased fat § This is not always the case – WHY? z Positive Health Aspects of Vegetarianism: Cardiovascular Health § Plant based diets = lower SFA intake than diets that include high fat meats § More MUFAs and PUFAs than SFAs § Nuts/seeds/soybeans § High fibre intake § Grains/vegetables/fruits/beans/legumes § Increased Phytochemicals to lower cholesterol § Vegetables/beans § More extreme difference in vegans z Positive Health Aspects of Vegetarianism: Cancer Defense § Correlates between foods not chosen and cancer = decreased incidence of cancer § Lack of red meat and processed meat in diet § Correlates between food eaten and cancer prevention § Fibre § Fruits/Vegetables (antioxidants) § Depending on types of vegetarianism, may lack vitamin D – correlate to colon cancer  z Possible Negative Health Aspects of Vegetarianism/Veganism § Low quality protein/lack of protein § Low iron § Low B12 § Inadequate calcium and vitamin D intake (if lack of milk product consumption) § What can be done? § Overall, need more attention to food choices and combinations to prevent deficiencies § May need supplementation  z Nutrients of Interest: Protein/Fat § Protein § Quality § Total amount needed § Additives § Preparation time and techniques § Complete vs. Incomplete § Omega-3 Fatty Acids § Lack of slows production of EPA and DHA in the body § Nuts/seeds/vegetables oils/omega fortified products help to compensate  z Nutrients of Interest: Minerals § Iron § Heme vs. Non-Heme § DRI: 1.8 times usual recommendation § Careful with calcium, tea, and tannins § Eat with vitamin C sources § Zinc § More absorbable from animal sources § Soy interferes with absorption § Deficiency seen more in children vegetarians/vegans § Calcium (for those who avoid milk products)  z Nutrients of Interest: Vitamins § Vitamin B12 § Only in animal derived foods and some fermented soy products § Fortified foods or supplementation necessary § Vitamin D (for those who avoid milk products) § Most concerned for infants/children/elderly and those in Northern climates  z Planning a Vegetarian Meal § Choose whole foods as opposed to processed as much as possible § Bananas, not banana chips § Plan complete meals § Carbohydrate (Whole grain/Fruit/Milk) § Complete Protein (Bean/Nut/Seed/Milk Product/Egg/Fish) § Fat (Avocado/Nuts/Seed/Oil) § Choose fortified products § May need to supplement  z Nutritional Genomics § Nutrigenomics vs Nutrigenetics § Caution over some tests clinical and/or scientific validity § Working on the human proteome § Identify proteins made by genes § Identify genes associated with aging and disease § Dietary and lifestyle choices that influence gene expression § GOAL: customize recommendations that fit the need of each individual  z Genomics Primer § Estimate 20,000 – 25,000 protein-coding genes in the human genome § Gene expression: genetic information (DNA) à protein synthesis (mRNA) § can measure mRNA on tissue sample § Patterns can help to explain disease development and relationship between diet and disease § Having a certain gene does not mean that the trait will be expressed § Nutrients activate or silence expression z Epi-genetics: § Epi-genetics: How environmental factors influence gene expression § Methylation: addition of methyl group to DNA or proteins § Can impact how molecules act § Whether or not a protein is made § Turn off gene expression § Ongoing research to determine which nutrients act on which genes z Genetic Variation & Disease § No one has the same DNA, except identical twins § Even in twins – a gene may be active or silenced thus causing different outcomes § Explains why some people respond to dietary interventions and others do not § Low SFA diet and cholesterol levels § Omega-3 supplementation (DHA/EPA) and TG levels § Some respond, some do not § Studies don’t generally consider genetics  z Gene Disorders Single Gene Disorders § Mutation of one gene at birth § Missing/malfunctioning protein = altered metabolism, need for strict dietary interventions § Phenylketonuria (PKU) § Mutation in gene that codes the enzyme that converts EAA (phenylalanine) to tyrosine § Results in build up of phenylalanine à nervous system (seizures, mental impairment) § Tyrosine becomes conditionally essential § Intervention: diet that restricts phenylalanine and supplies tyrosine  z Gene Disorders Multi-gene Disorders § Several genes influence disease progression § Not caused by a single gene on its own § Complex to study § Must determine interactions of multiple genes, as well as multiple environmental influences § Heart Disease § Multiple risk factors (DM, elevated LDL, obesity) § Each risk factor has multiple genetic and environmental causes § Research on genetic variations among people § Most common is single-nucleotide polymorphisms (SNPs)