Advanced Nutrient Metabolism I Fall 2024 PDF

Advanced Nutrient Metabolism I Fall 2024  Proteins Blood stability Muscles Centers for biochemical rxns Signaling Enzymes (hormones an...

Advanced Nutrient Metabolism I Fall 2024  Proteins Blood stability Muscles Centers for biochemical rxns Signaling Enzymes (hormones and cytokines) Structure Recommendations? What are the protein recommendations? https://www.cdc.gov/nchs/data/hus/2020-2021/mcrnutr.pdf Proteins Proteins: 16% N Body protein: made of 20 amino acids Amino Acids Amino Acids Protein Synthesis https://www.youtube.com/watch?v=oefAI2x2CQM van Sadelhoff et al(2020) Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in th Protection Against Neonatal Allergies and Infections. Front. Immunol. 11:1007. doi: 10.3389/fimmu.2020.0100 Body Amino acid Pool  Phase 1- Gastric digestion Phase 2- Digestion by pancreatic proteases Digestion Phase 3- Digestion at the brush border https://pressbooks.bccampus.ca/nutr1100/chapter/protein-digestion-and-absorption/  Dietary Protein Phase 1- Gastric digestion Figure 2. Gastric digestion Gastric Chief of dietary protein. Cells Pepsinogen denaturation by stomach acid autoactivation (intramolecular hydrolysis by pepsin cleavage) Pepsin autocatalysis large peptide fragments free amino acids aa aa Pyloric sphincter aa aa Duodenum Acid from parietal cells denatures protein to be more susceptible to pepsin cleavage. Pepsinogen activated to pepsin by autoactivation and autocatalysis by pepsin. Large peptide fragments/some amino acids pass through the pyloric sphincter to the duodenum  Phase 2- Digestion by pancreatic proteases Duodenal Endocrine free amino acids Duodenal Cell from gastric digestion Endocrine CCK-PZ Cell CCK-PZ Trypsinogen Entero- peptidase (hydrolysis) Blood- stream Trypsin Pancreatic Acinar Cell Mucosal Epithelial Cells Figure 3. Secretion, activation and action of pancreatic proteases and brush border endopeptidases and aminopeptidases  Phase 2- Digestion by pancreatic proteases Duodenal Endocrine Duodenal free amino acids Endocrine Cell from gastric Cell digestion CCK-PZ CCK-PZ Trypsinogen Secretin Entero- peptidase (hydrolysis) Blood- autocatalysis stream Trypsin Pancreatic Acinar Cell HCO3- Mucosal neutralizes Epithelial acid Cells Figure 3. Secretion, activation and action of pancreatic proteases and brush border endopeptidases and aminopeptidases  Phase 2- Digestion by pancreatic proteases Duodenal Endocrine Duodenal free amino acids Endocrine Cell from gastric Cell digestion CCK-PZ CCK-PZ Trypsinogen Secretin Entero- peptidase (hydrolysis) Blood- autocatalysis stream Trypsin Chymotrypsinogen Proelastase Pancreatic Procarboxypeptidases Acinar Cell catalysis HCO3- Mucosal Chymotrypsin neutralizes Epithelial Elastase acid Cells Carboxypeptidases Figure 3. Secretion, activation and action of pancreatic proteases and brush border endopeptidases and aminopeptidases Figure 3. Secretion, activation and action of pancreatic proteases and brush border endopeptidases and Phase 2- Digestion by pancreatic proteases aminopeptidases Phase 3- Digestion at the brush border Duodenal Endocrine Duodenal free amino acids Endocrine Cell from gastric digestion Cell CCK-PZ CCK-PZ Trypsinogen Secretin Entero- peptidase (hydrolysis) Blood- autocatalysis stream Trypsin Chymotrypsinogen Proelastase Pancreatic Procarboxypeptidases Acinar Cell catalysis HCO3- Mucosal Chymotrypsin neutralizes Epithelial Elastase acid amino acids Cells Carboxypeptidases dipeptides tripeptides brush border endo-/aminopeptidases hydrolyze products; amino acids, di-/tripeptides absorbed by epithelial cells  LUMEN OF INTESTINE Amino acids Na+ Di-, tri- peptides Intestinal Epithelium Phase 4 - Absorption Dipeptides, tripeptides Brush border Dipeptidases, tripeptidases Amino acids Na+ 2K+ 3Na ATP contraluminal membrane ADP + Pi 3Na+ 2K+ = Na+-dependent co-transport = Na+,K+-ATPase Figure 4. Absorption of amino acids and di- and tripeptides from the intestinal lumen  Amino acids Na+ Di-, tri- LUMEN OF INTESTINE peptides Phase 4 - Absorption Intestinal Epithelium Dipeptides, tripeptides Brush border Dipeptidases, Phase 5 tripeptidases Amino acids 3Na+ 2K+ ATP    contraluminal membrane ADP + Pi  Phase 5   capillaries 3Na+ 2K+ = Na+-dependent co-transport = Na+,K+-ATPase = facilitated diffusion Figure 4. Absorption of amino acids and di- and tripeptides from the intestinal lumen Amino Acid Transport https://education.med.nyu.edu/mbm/aminoAcids/digestionAbsorption.shtml  PATHWAYS OF AMINO ACID SYNTHESIS AND DEGRADATION https://doctorlib.info/medical/biochemistry/21.html Pathways of AA Metabolism  aminotransferase alpha-ketoglutarate Glutamate Pathways of AA Metabolism alanine aminotransferase aspartate aminotransferase Pathways of AA Metabolism https://www.youtube.com/watch?v=qVd2H3Vt jAA Pathways of AA Metabolism Pathways of AA Metabolism Pathways of AA Metabolism Pathways of AA Metabolism  Turnover of proteins in the Body Proteins are in constant rate of synthesis and breakdown: Turnover Turnover rate depends on the protein type ◦ High rate of turnover: Proteins with regulated concentrations or that act as signals ◦ Low rate of turnover: Structural proteins Non growing healthy adults with stable weight: balance between breakdown and synthesis  N balance METHODS OF MEASURING PROTEIN TURNOVER: N balance METHODS OF MEASURING PROTEIN TURNOVER: N balance METHODS OF MEASURING PROTEIN TURNOVER: N balance METHODS OF MEASURING PROTEIN TURNOVER: N balance METHODS OF MEASURING PROTEIN TURNOVER: N balance  Tracer Methods Defining Amino Acid Kinetics isotopically labeled tracers are used Radioactive isotopes: e.g., 3H for hydrogen and 14C for carbon Stable isotopes: eg., 2H for hydrogen and 13C for carbon  Tracer Methods Defining Amino Acid Kinetics At steady state of tracer concentration: Q (Flux) = I+B=C+S Tracer Methods Defining Amino Acid Kinetics The simplest models consider only IDAAs: no de novo synthesis components. The kinetics of IDAAs mimics the kinetics of protein turnover Ex: L-[1-13C]leucine tracer Tracer Methods Defining Amino Acid Kinetics The rates of amino acid release from protein breakdown: B = Q-I The rates of amino acid uptake for protein synthesis: S= Q-C components are then extrapolated to whole body protein kinetics by dividing the amino acid rates by the assumed concentration of the amino acid in body protein  Net: D>S Net: S>D James, H. A., O'Neill, B. T., & Nair, K. S. (2017). Insulin regulation of proteostasis and clinical implications. Cell metabolism, 26(2), 310-323. James, H. A., O'Neill, B. T., & Nair, K. S. (2017). Insulin regulation of proteostasis and clinical implications. Cell metabolism, 26(2), 310-323. Fed State Dietary intake of amino acids and glucose are used to replete protein and glycogen that were lost during the postabsorptive period Intake in amounts greater than what is needed to replete nighttime losses is either oxidized or stored to increase protein, glycogen, or fat for growth or for storage of excess calories. Recommended Dietary Allowances for Protein  Amino Acid Requirements Classical N balance studies require 7 to 10 days for equilibration to occur in urinary N output, but this constraint is not required when using the indicator tracer to measure oxidation directly Amino Acid Requirements  Protein and Amino acids in disease In disease (infection, burn, surgery, trauma) metabolic rate rises body protein is mobilized for use as a fuel (amino acid oxidation) and for supply of carbon for gluconeogenesis. May be significant in old and chronic illness Supplying additional nutrients (some AAs become essential) either enterally or parenterally may blunt, but will not reverse, the N loss seen in injury Add insulin and growth hormone to improve synthesis Addition of single amino acids Glutamine: fuel by gut cells and synthesis of nucleotides Ariginine: precursor of nitric oxide, important for immunity & healing Controversial Protein Controversies? HIGH PROTEIN INTAKE & RENAL FAILURE IS IT A GOOD IDEA TO LOSE WEIGHT ON A HIGH PROTEIN DIET? Protein intake and bone health