1. Macronutrients****************Proteins

2. Protein Nutrition and Metabolism In the U. S. and other industrialized nations average adult consumes ~100 g protein/day This accounts for about 12% of daily caloric need This is about 2x the RDA set by the U. S. and other countries and agencies Intake of protein in U. S. has remained rather constant since 1900, when it was ~10% of consumed calories However, proportion of animal protein has more than doubled in the intervening period

3. Protein malnutrition, also called Kwashiorkor, is a common problem in less developed countries where meat, fish and other good sources of protein are scarce

4. In addition to ingested protein, another ~70g/day of protein enters digestive system via gastric and intestinal juices, digestive enzymes, and cells sloughed from lining of gastrointestinal tract Note: life span of the gastrointestinal mucosal cell is about 3-4 days; this means that 1/4 to 1/3 of these cells are sloughed daily Of this daily total of ~170 g of protein entering digestive tract, about 1.6 g total N (=10 g protein) is excreted in the feces Remaining 160 g of protein enzymatically hydrolyzed to amino acids and small peptides

5. Dipeptidases in intestinal epithelium cleave di- and tripeptides to free amino acids The amino acids subsequently absorbed into intestinal epithelial cells and cleared by hepatic portal system to the liver and peripheral tissues Note: a significant portion of amino acids absorbed by intestinal epithelium is used by the intestine itself for protein synthesis, including that needed for replacement of lost cells

7. Indispensible Amino Acids also called Essential Amino Acids

8. Branch chain AAsAromatic AAs Val His Lys Ile Leu Met Thr Trp Phe Basic AAs Other AAs Indispensible Amino Acids

9. Much, but not all, of the methionine requirement can be replaced by dietary cysteine, since there is a pathway for conversion of MET to CYS Much, but not all, of the phenylalanine requirement can be replaced by dietary tyrosine, since there is a pathway for conversion of PHE to TYR In this way CYS and TYR serve to “spare” requirements for MET and PHE, respectively

10. Arginine is synthesized by humans, but not at a rate to meet needs during times of rapid growth infancy and childhood pregnancy

11. Dietary Protein Requirement In 1985, WHO/FAO/UNO set daily protein requirement for adults at 0.75g/kg body wt This has been accepted by U. S. and Canadian governments Current (2002) RDA is 0.80 g/kg “ideal body weight” per day for adults This is 56 g/day for adult males and 46 g/day for adult females in U. S.

12. These estimates of requirements derived from measurements of normal daily N losses (feces, urine, sweat, other body fluids, skin, hair) balance studies comparing relative daily intake and loss are compared at different low levels of protein intake and the results compared and extrapolated to give a minimal requirement

13. Note: There are significant differences in protein RDA as a function of age and during pregnancy and lactation For example, infants from birth to 6 months of age have a protein AI of 9.1 g/day (1.52 g/d/kg body weight)  See “Protein DRI 2002” table on p. 3, Macronutrient-III handout

16. Sources of Protein and Protein Quality Numerous studies carried out to determine normal human requirements for individual essential amino acids This has led to the formulation of a so-called “ideal” protein  cf., Table 4.2, Macronutrient-III handout, p. 5

17. Proportion of essential amino acids in “ideal” protein similar to that found in eggs and milk proteins In general, proteins from animals, including fish and fowl, have good proportions of essential amino acids Except for soybean protein, most plant proteins do not meet the ideal and usually are short of ideal in one or two of the essential amino acids

18. Grains and nuts tend to be low in lysine and, sometimes, tryptophan Legumes tend to be deficient in sulfur amino acids, although they are important as concentrated protein foods As a consequence, care must be taken to combine vegetable proteins to insure combinations will supply adequate amounts of essential amino acids

19. For example, black beans are deficient in sulfur amino acids, while corn meal is deficient in lysine and tryptophan However, in appropriate combination, black beans and corn meal constitute a complete “ideal” protein

21. This is of special importance to pure vegetarians (vegans) who have no milk or egg protein in their diets. However, this seems not to be a problem in the U. S. where vegans eat considerably more protein than they require, thus making up for deficiencies in any specific essential amino acid

23. Nitrogen Balance Some important relationships to remember: Protein = 16% N Therefore: 0.16 x g protein = g Nor 6.25 x g N = g protein

24. To do a completely accurate N balance study on an individual would require measuring all sources of N loss from the body. This is very difficult even in research setting and, pragmatically, is not possible in clinical setting

25. What is used are estimates based on estimating protein intake per day from standard tables of nutrient content for various foods and comparing that to the total N excreted in feces and urine or, more commonly comparing the N in a 24-hour urine sample and estimating the non-urinary N losses from literature values

26. In clinical setting, the procedure involves use of an empirically derived formula – N balance =(Protein intake/6.25) – [(1.25 x urinary urea N) + 4](grams) (grams) NOTE: 1.25 corrects for the fact that not all urinary N is in form of urea 4 grams added are estimate of N loss by non- urinary routes

27. Nitrogen balance (N in - N out ) is positive for: growing infants and children pregnant or lactating women or body-building adult when there is tissue growth or replenishment such as recovering from metabolic stress or nutritional deficiency  Adults receiving a minimally adequate or greater amount of protein will be at zero balance, where input = output

28. (a) Positive N balance growth, lactation, recovery from metabolic stress Adapted from Devlin, 5/e (2002) fig. 26.1

29. Negative N balance occurs: in fasting or starvation when there is no or inadequate protein intake in pathological conditions (burns, traumatic injury, fevers) and in severe psychological stress

30. These are all conditions in which body function is diverted or activity reduced relative to the normal (bed confinement causes muscle atrophy) and/or conditions when there is abnormally high secretion of glucocortico-steroids (which causes catabolism of muscle protein)

31. (b) Negative N balance metabolic stress Adapted from Devlin, 5/e (2002) fig. 26.1

32. (c) Negative N balance inadequate dietary protein Adapted from Devlin, 5/e (2002) fig. 26.1

33. It should also be noted that no matter how much protein is ingested, if there is an essential amino acid deficiency, there will be a negative protein balance This is because the other amino acids absorbed cannot be used for protein synthesis to replace those proteins lost during normal daily protein turnover.

34. (d) Negative N balance lack of an essential amino acid Adapted from Devlin, 5/e (2002) fig. 26.1

35. The daily requirement for dietary protein may more than double, both acutely and long term, for patients with burns or injuries to support tissue healing. Requirements also may be increased in terminal cancer and total parenteral nutrition (TPN, formerly called hyperalimentation) for such patients is often carried out (no evidence that it prolongs life).

36. On the other hand, restricted (decreased) protein intake is indicated in the treatment of persons with liver, kidney, or intestinal diseases, since these organs are highly involved in the absorption, breakdown, and excretion of protein metabolites

37. Short Term Effects of High Protein Meal During absorptive phase following eatinga high protein, low carb meal get:  increase in glucagon secretion (due to low blood glucose)  also have increase in insulin secretion, but much lower than found following typical carbohydrate-containing meal

38. Increased insulin is sufficient to promote protein synthesis, but not high enough to prevent gluconeogenesis Overall outcome is that amino acids can be used for protein synthesis and gluconeogenesis, oxidized for energy, or possibly stored as glycogen and fat

40. Fig. 26.8 Fig. 26.12