Protein Requirements and Function PDF

Designing Parenteral/Intravenous Regimens delivering aa to peripheral veins —> bypassing the liver • Metabolism • Bypass splanchnic control glucose and aa a lot of constraint for aa —> some aa are not soluble (tyrosine) and some are not stable (glutamine —> an important aa), cysteine will oxidiz...

Designing Parenteral/Intravenous Regimens delivering aa to peripheral veins —> bypassing the liver • Metabolism • Bypass splanchnic control glucose and aa a lot of constraint for aa —> some aa are not soluble (tyrosine) and some are not stable (glutamine —> an important aa), cysteine will oxidized in cystine and will precipitate • Composition • Free AAs • Solubility • Stability Lipids: emulsify oil In the IV: Glucose, aa, vitamins and minerals Designing the optimal AA Profile: First step - Aromatic AAs issues for babies: high levels which is potentially toxic Issues: tyrosine insolubility, transient hyperphenylalaninemia and hypertyrosinemia If not enough: give more phenylalanine PHENYLALANINE 1 2 TYROSINE give precursor that is more soluble N-acetyltyrosine content is really low give another precursor 3 Protein Synthesis Catabolism Glycyl-tyrosine Nitrogen Retention i.e. N Balance as a % of N intake 100 % of nitrogen intake retains more nitrogen and gaining more weight : suggests that tyrosine was a limited aa done on baby pigs 70% retaining really fast bc fast growth Healthy adult: 0% retained bc 0 nitrogen balance Piglets: 2000, can’t metabolize the extra phenylalanine faster —> not the good solution for infants We could add phenylalanine to see tyrosine specifically —> uses the extra Piglets: 100 phenylalanine Piglets: 100 GT was effectively used, but really expensive didn’t use NAT: just excreted it 80 70% % 60 40 20 0 clinically available solution Vamin increase [phenylalanine] Vaminolact same as vermin but for breast milk VL+PHE VL+NAT VL+GT Body weight gain of infants rapid period of growth in the first 6 months Body weight gain in young piglets fed a protein deficient diet Piglets (Well Nourished) 100%: 3 to 6 kg 101% 50% 66% 18% 15%: don’t gain weight how much of their initial bodyweight they gained Means ± SEM, n=8, p<0.05 Protein requirement • DRI report based on N balance studies • EAR = 0.66 g/kg/d • RDA = 0.80 g/kg/d 70 kg standard for men: 56 grams 55 kg for women Typical intake in america: 80/100 grams FIGURE 2. Relation between various nitrogen intakes and the mean nitrogen balances from 28 nitrogen balance studies (data from references quoted in Table 3) EAR RDA + SD Humayun, M. A et al. Am J Clin Nutr 2007;86:995-1002 Copyright ©2007 The American Society for Nutrition FIGURE 3. Hypothetical example of the relation between various protein intakes and nitrogen balances (true and 10% overestimated) We were crossing line at wrong point Humayun, M. A et al. Am J Clin Nutr 2007;86:995-1002 Copyright ©2007 The American Society for Nutrition Testing AA requirement by IAAO 120 Indicator PHE 80 Test AA LYS % of requirement 100 60 40 20 0 At Reqt Limiting Testing Protein Requirement by IAAO 120 At req= all AA in excess, one is limiting (lysine) The oxidation changes as we increase intake of limiting aa = decreased oxidation Indicator PHE % of requirement 100 80 60 diet intervention: Phe (indicator) and change level of all aa together 40 20 0 At Reqt Limiting Relation between various protein intakes and the rate of appearance of orally administered L-[1-13C]phenylalanine as breath 13CO2 in 8 healthy men EAR RDA oxidation dose Humayun, M. A et al. Am J Clin Nutr 2007;86:995-1002 Copyright ©2007 The American Society for Nutrition Table 1 Evidence that protein requirements have been significantly underestimated. Elango, Rajavel; Humayun, Mohammad; Ball, Ronald; Pencharz, Paul Current Opinion in Clinical Nutrition & Metabolic Care. 13(1):52-57, January 2010. DOI: 10.1097/MCO.0b013e328332f9b7 results with oxidation approach Table 1 Comparison of protein requirement estimates in adult humans © 2010 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2 FIGURE 1 Protein Requirement in elderly women The Journal of Nutrition, Volume 146, Issue 4, April 2016, Pages 681–687, https://doi.org/10.3945/jn.115.225631 The content of this slide may be subject to copyright: please see the slide notes for details. Protein Requirement in endurance-trained young men each individual has its own breakpoint . Protein intake and phenylalanine (Phe) oxidation in young endurance-trained men (43 experiments). Individual values for each athlete are represented by different symbols. The Fig. 2 breakpoint represents the estimated average requirement (EAR) for protein. A mixed-effects change-point regression analysis identified a breakpoint (EAR) and upper 95% CI for the relation between protein intake and Phe oxidation to be 2.1 and 2.6 g·kg−1·day−1 (r2 = 0.68), respectively. d, day. https://journals.physiology.org/doi/pdf/10.1152/ajpendo.00174.2018 Protein Balance in endurance-trained young men same group but with net phenylalanine balance : same breakpoint Relationship between protein intake and net phenylalanine (Phe) status in young endurance-trained men (43 experiments). Individual values for each athlete are represented by different symbols. The breakpoint represents the estimated average requirement (EAR) for Fig. 3. protein. A mixed-effects change-point regression analysis identified a breakpoint (EAR) and upper 95% CI for the relation between protein intake and net Phe status to be 2.1 and 2.6 g·kg−1·day−1 (r2 = 0.65), respectively. d, day. https://journals.physiology.org/doi/pdf/10.1152/ajpendo.00174.2018 DOI: (10.1152/ajpendo.00174.2018) Protein Requirement in Endurance Athletes Lower breakpoint Kato H, Suzuki K, Bannai M, Moore DR. Protein Requirements Are Elevated in Endurance Athletes after Exercise as Determined by the Indicator Amino Acid Oxidation Method. PLoS One. 2016;11(6):e0157406. Published 2016 Jun 20. doi:10.1371/journal.pone.0157406 Protein Requirements Are Increased in Endurance-Trained Athletes but Similar between Females and Males during Postexercise Recovery • WILLIAMSON, ERIC; FUNG, HUGO J. W.; ADAMS, CAROLYN; WEST, DANIEL W. D.; MOORE, DANIEL R. Medicine & Science in Sports & Exercise55(10):1866-1875, October 2023. doi: 10.1249/MSS.0000000000003219 important to get different studies to replicate data and bring it all together and establish new recommendations Both have breakpoint around 1.5 Relationship between protein intake and PheOx for males (A) and females (B), and breakpoints for each sex (C). Each line in A and B represents the individual biphasic regressions of each participant. Data in panel C are presented as mean ± SD. Copyright © 2023 Wolters Kluwer. Published by Lippincott Williams & Wilkins. 17 Protein intake and function Men EAR • Feed 0.6 or 0.75 vs 1.0 g protein /kg/d for 7 days in men • Lower protein intakes show: • Decrease in: • Protein turnover • Glutathione synthesis • Antioxidant capacity, increased susceptibility to oxidative stress • Albumin synthesis (negative acute phase protein) • Increase in: • Fibrinogen synthesis (positive acute phase protein) act as a defence • Suggests: • moderate protein deficiency results in a minor stress response? • Current EAR and RDA are too low Do athletes need more protein? More than the RDA? YES – but so does everyone Note that most people consume much more than the RDA More than they would get in their normal diet? Probably not or at least not much Timing: more important Isonitrogenous meals Post-exercise Breaking fast with breakfast with 30 grams in the morning to maximize protein synthesis Post-exercise: CHO, fluid, water New Protein Recommendations Academy of Nutrition and Dietetics, Dietitians of Canada and the American College of Sports Medicine recommend 1.2 to 2.0 grams of protein per kilogram of body weight per day for athletes, depending on training. Protein intake should be spaced throughout the day and after workouts. Phillips and Van Loon J Sports Sci. 2011;29 Suppl 1:S29-38. “There is a good rationale for recommending to athletes protein intakes that are higher than the RDA. Our consensus opinion is that …. protein intakes in the range of 1.3-1.8 g/kg/d consumed as 3-4 isonitrogenous meals will maximize muscle protein synthesis. These recommendations may also be dependent on training status: experienced athletes would require less, while more protein should be consumed during periods of high frequency/intensity training. Elevated protein consumption, as high as 1.8-2.0 g/kg/d depending on the caloric deficit, may be advantageous in preventing lean mass losses during periods of energy restriction to promote fat loss.” hard to study Protein Requirement in Critical Illness • 2022: Critically Ill infants in NICU • IV amino acid supplement to 4 g/kg/d for 5 days • No effect on neurodevelopment long term • 2021: Critically ill ventilated adults in ICU • IV amino acid supplement to 2.5 g/kg/d • Moderate increase in N balance, protein synthesis extra protein or not ? • Equipoise doa lotweofneed research going on in this area Indirect Calorimetry • Basal Metabolic Rate • Thermic Effect of Feeding • Hypermetabolism • Substrate Utilization • Respiratory quotient • RQ = RER Role of different organs in the metabolism of AAs • Digestion • Pepsin in stomach – acid pH • Proteases from pancreas in small intestine – luminal digestion of peptide bonds • Peptidases on brush border of intestinal epithelial cells • Active transporters for absorption Did not see it in class Liver Gut Pancreas Muscle Did not see it in class Liver Gut Pancreas Muscle Did not see it in class Liver Gut Pancreas Muscle Liver Muscle important for protein metabolism bc there is so much • 3% BW • 40% BW • 21% BMR • 21% BMR • 30% body’s protein synthesis • 30% body’s protein synthesis • 50% of proteins newly synthesized each day • 3% of proteins newly synthesized each day Proteins in urea cycle: half life 11 minutes half life: 1 month Liver Anabolic Catabolic – Constitutive protein synthesis – Plasma protein synthesis – Gluconeogenesis – Lipogenesis – AA catabolism – Urea cycle most protein in plasma made by liver: albumin fibrinogen: that will become fibrin (non soluble) function: detoxify