Proteins

1. Proteins One of the most Versatile Organic Molecules

2. What do you Already Know About Protein Structure? • What are the building blocks (subunits) that make proteins? • How many of these subunits are there? • How are the subunits held together? • What are the levels of structure of proteins?

3. Excess dietary protein cannot be stored in body. • Proteins contain nitrogen (N) as well as C, H and O, • Some contain sulfur (S)

4. Proteins • Proteins are essential components of every cell • Proteins-contains C, H, N, O essential for cell functions • Amino Acids are the building blocks (subunits) of proteins. • Amino Acids contain an amine group on one end and a carboxyl group on the other.

5. Amino Acids • Composed of central C bonded to 4 groups • Amino group: -NH2 • Carboxyl group: -COOH • Hydrogen: -H • R group: is the variable in structure • Essential AA’s are those that cannot be synthesized from other AAs in humans, must be consumed • Non-Essential AAs- can be synthesized from other AAs in the human body

8. Dehydration Synthesis and Hydrolysis Rxns

9. Proteins are Classified by # AA’s in chain • Dipeptides: 2 amino acids • Tripeptides: 3 amino acids • Polypeptides: More than 10 amino acids • Peptides: Fewer than 50 amino acids • Proteins: More than 50 amino acids • Typically 100 to 10,000 AAs linked together

10. The 20 Amino Acids

11. The Organization and Shape of Proteins Affect Their Function • 4 Levels of Structure • Primary structure: Amino acids are linked together to form a simple linear chain. • Secondary structure: Geometric shape of the protein that is folded and twisted • Tertiary structure: Three-dimensional globular shape of the protein • Quaternary structure: Two or more polypeptide chains bond together.

12. 4 Levels of Protein Structure α-Helix β-Pleated Sheet 3-D Shape R group Interactions Not all Proteins (H bonds)

13. Denaturation Shape of Proteins • Denaturation (unfolding) of proteins occurs in the presence of: • Heat • Acids • Bases • Salts • Mechanical agitation • Altering the shape of the protein alters its function. • Primary structure is unchanged by denaturing.

14. Denaturing a Protein

15. Protein Synthesis Transcription is the process of making an RNA copy of a gene sequence, called a messenger RNA (mRNA). This occurs in the nucleus of the cell. Translation is the process of translating the sequence of mRNA to a sequence of amino acids that will result in a protein. This occurs in the cytoplasm of the cell with ribosomes and tRNA. Ribosomal RNA (rRNA) is also involved in translation. *Sequencing errors can cause alterations in proteins to be made; an example is sickle-cell anemia.

17. Stages of Translation • Initiation- bring together all of the materials required for protein synthesis • Elongation- sequential addition of amino acids in the order specified by the mRNA • Termination- release of completed protein from the ribosome

18. Codon-Anticodon base pairing occurs for assembly of amino acid into protein

19. Basic Steps in Protein Synthesis 1. DNA unwinds in nucleus allowing a copy of a gene to be made messenger RNA (mRNA) = Transcription 2.The mRNA moves the cytoplasm and becomes associated with ribosomes. 3. Transfer RNA (tRNA) brings in the specific amino acid called for by the mRNA = Translation 4. Translation continues, as incoming amino acids form a growing peptide and protein chain = Elongation 5. Protein synthesis is terminated and the completed protein is release from ribosomes = Termination

20. Digesting and Absorbing Proteins • Chewing Proteins in Mouth – Mechanical Digestion • Bolus goes down esophagus & enters stomach. • Chemical Digestion of Protein begins in Stomach. • Gastrin stimulates the release of HCl. • HCl from parietal cells in stomach trigger activation of pepsinogen to pepsin. • Pepsin breaks polypeptides into shorter chains. HCl Pepsinogen Pepsin (inactive) (active) Gastrin - peptide hormone made by stomach, duodenum, pancreas; aids in gastric motility

21. Enzymes involved in Protein Digestion

22. Digestion continues in Small Intestine Polypeptides broken down into tri- and dipeptides. • Cholecystokinin (CCK) stimulates the release of proteases by the pancreas. • Proteases break peptides to tripeptides & dipeptides. • Dipeptidases and tripeptidases break the dipeptides and tripeptides into amino acids. CCK - peptide hormone of small intestine stimulates digestion of protein and fat; acts as a hunger suppressant.

23. Absorbing Proteins • Amino acids transported to liver from the intestines via the Hepatic Portal Vein. • In the liver, amino acids are: • Used to synthesize new proteins • Converted to E, glucose, or fat • Released to bloodstream and transported to cells in entire body • Amino acids absorbed in Small Intestine • Occasionally proteins are absorbed intact.

24. Amino Acid Metabolism • Liver metabolizes AA’s • depending on bodily needs • Most AA’s sent into circulation for use by cells muscle skin collagen membranes enzymes transporters • If ↓ carbs, AA’s converted into glucose* Gluconeogenesis

25. Metabolic Fate of Amino Acids Amino Acid Pool AA Pool = supply for body's ongoing needs

26. Protein Turnover – Tap into AA’s Pool • Body constantly makes and breaks down proteins • Body degrades ~300g pro-/day: we take in ~65-90g • Most AA’s recycled to build new proteins • Some are eliminated in feces or urine • Some proteins broken down for energy • Hormones can alter protein synthesis • Insulin and Growth Hormone increase protein syn. • Glucagon and Cortisol increases protein breakdown.

27. Deamination = Removal of the Amine Group from Amino Acids (AA loses an amino group without transferring it to another molecule) • When this occurs Ammonia (NH3) is formed. • NH3 converted to Urea by Liver, urea then excreted in urine. • The C remnants are: • Converted to glucose… • Converted to fatty acids (→triglycerides in adipose tissue) glucogenic amino acids ketogenic amino acids When AA pool reaches capacity, the AAs broken down for other uses.

28. Using Amino Acids as Fuel

29. Transamination = Forming Nonessential Amino Acids by transferring the N from one amino acid to a keto acid to form a new nonessential amino acid.

30. Functions of Protein in the Body • Provide Structural Support – e.g., collagen in skin • Enable Body Movement - e.g. muscle • Enzymes = Biological Catalyst • Act as a chemical messenger Hormones regulate cell actions, e.g. Insulin, glucagon. • Regulate Fluid Balance – create ‘colloid’ fluid of plasma (plasma proteins) Speed up Chem Rxns

31. An Enzymein Action Substrates Becomes different Products

32. Functions of Proteins • Transportation in body – e.g., lipoprotiens, cell memtransporters… (ions, glucose) • Contribute to a healthy immune system • Antibodies bind and neutralize pathogens. • Help maintain acid-base balance (H and OH) • Provide Eergy - 4 kcals/gram • Improve satiety and appetite control

33. Proteins as Transporters

34. The Many Roles of Proteins

35. Amino Acid Metabolism

36. Protein Turnover continual making and breaking down of • proteins in the body. Forms the amino acid pool: • Exogenous amino acids from food • Endogenous amino acids from within the body • 2. Nitrogen Balance = Protein utilization in the body. • Zero N balance in equilibrium. • Positive N balance - N consumed is greater than excreted. • Negative N balance - N excreted is greater than consumed. • 3.Amino Acids to make Proteins or Non-Essential AAs • 4.Amino Acids to Make Other Compounds • Neurotransmitters (e.g., tyrosine, glutamate, glycine…). • Tyrosine made into melanin or thyroxine. • Tryptophan needed to make niacin and serotonin.

37. 5. Using Amino Acids for Energy and Glucose No readily available storage form of protein Break down of protein in tissue for energy if needed 6.Deamination of Amino Acids - N containing amino groups removed, 2 products result ammonia and keto acids. 7. Using Amino Acids to make Proteins or Nonessential Amino Acids (Transamination) 8. Converting Ammonia to Urea. Deamination of AAs yields toxic ammonia NH3. Liver converts NH3 to Urea carbon dioxide (CO2). 9.Excreting Urea. Urea into bloodstream goes to the kidneys and is excreted in urine. ↑ H2O necessary with high-protein diet to flush excess urea from body. Excess protein is de-aminated and converted into fat.

38. Phenylketonuria (PKU) Caused by very low or absent levels of enzyme Phenylalanine Hydroxylase (PAH) • Results in decreased ability to metabolize Phenylalanine (Phe) • PAH enzyme converts Phe  Tyrosine (Tyr) • If cannot, then both Phe and Tyr must be obtained from diet • Person with PKU must carefully regulate intake of Phe • If Phe and its products (phenylpyrivic acid) build up, it can cause mental retardation, seizures & nervous system damage.

39. Proteins in Food • Good sources of proteins include • Red meat • Tuna • Poultry • Milk • Fish • Beans and other legumes • Nuts

40. Nitrogen Balance and Imbalance

41. Most Americans consume enough protein in their diet • Those growing or ill require larger amounts of protein. • Calculation of N balance is used to determine protein equilibrium. • Excess protein cannot be stored and is converted into glucose or fat for later use. • Athletes who are highly trained for endurance activities may need to exceed the RDA for protein. Protein Needs

42. Proteins in Foods • In North America 70% of our protein comes from animal sources. • Vegetable sources of protein contain more fiber and minerals than animal sources • Dried foods such as nuts and beans can be good sources of protein, fiber and minerals • Animal protein has all 9 essentialAA, plants do not • High-quality proteins- animal proteins contain all proteins we need in sufficientamounts • Lower-quality proteins- plant proteins lack one or more AA we need

43. 5 Brain Nutrients Found Only in Meat, Fish and Eggs (NOT Plants) 1. Vitamin B12- body can’t produce it! Water-soluble vitamin involved in function of every cell; blood and brain function. Deficiency: anemia, impaired brain function, symptoms of mental disorders and a smaller brain. 2. Vitamin D3 – from cholesterol in your skin and ultraviolet rays from the sun. Vit D2 (ergocalciferol) from plants but studies show D3 (cholecalciferol) from animals, is much more effective. Cod fish liver oil best source (also fatty fish). Deficiency: linked to depression, impaired immune system, cardiovascular disease and cancer, autoimmune disease, multiple sclerosis and cognitive impairment. 3. Creatine - in our skeletal muscle and brain cells, forms an energy reserve to quickly recycle ATP, not essential nutrient Liver can produce, but inefficiently. Deficiency adversely affects muscle and brain function 4. Docosahexaenoic Acid (DHA) - essential Omega-3 fatty acid - if we don’t eat them, we get sick. DHA most abundant Omega-3 fatty acid in the brain, critical for normal brain development (ALA needs to be converted to DHA for it to work). Fatty fish best source of DHA; also grass-fed and pastured animal products. 5. Carnosine - a dipeptide (histidine and beta-alanine) in both muscle tissue and brain, very protective against degenerative processes in body. A potent antioxidant, inhibits glycation caused by elevated blood sugars and may prevent cross-linking of proteins. Levels are significantly lower in patients with Parkinson’s and Alzheimer’s

44. Soy Protein – Best to Avoid all Non-Fermented Soy products List some important reasons why….

45. Types of Protein-Energy Malnutrition (PEM): Kwashiorkor • Severe Protein Deficiency • Generally the result of a diet high in grains and deficient in protein • Symptoms include: • Edema in legs, feet, and stomach • Diminished muscle tone and strength • Brittle hair that is easy to pull out • Lethargic • ↑infection, rapid heart rate, excess fluid in lungs, pneumonia, septicemia, and water and electrolyte imbalances

46. Types of PEM: Marasmus • Results from a severe deficiencyin calories (energy) • Frail, emaciated appearance • Weakened and lethargic • Often cannot stand without support • Appears old beyond years • Hair thin, dry, and lacks sheen • Low Tb and blood pressure • Prone to dehydration, infections, and blood clotting

47. Types of PEM: Marasmic Kwashiorkor • Chronic deficiency in Calories and Protein • Edema in legs and arms • A "skin and bones" appearance • With treatment, the edema subsides and appearance becomes more like someone with marasmus.

48. Treatment for PEM • Medical and Nutritional treatment can dramatically reduce the mortality rate. • Implemented carefully and slowly • Step 1: Address life-threatening factors. • Severe dehydration • Fluid and nutrient imbalances • Step 2: Restore depleted tissue. • Gradually provide nutritionally dense calories and high-quality protein. • Step 3: Transition to foods and more physical activity.

49. Evaluation of Protein Quality • Measure of ability of protein to support body growth and maintenance • Protein quality only valid under conditions where amount consumed meets or exceeds requirements for essential amino acids • Non-essential amino acids are used as energy sources or are degraded

50. Biological Value (BV) The Biological Value (BV) is a measure of how efficiently food protein, once absorbed from GI tract, can be turned into body tissue. BV depends on how closely its amino acid pattern reflects the amino acid pattern in body tissue. The better the match the more completely food protein is turned into body protein. Ex. Egg white protein: BV 100, highest BV of any single food protein.