Digestion of Proteins

1. Digestion of Proteins Absorption of amino acids

4. DIGESTION AND ABSORPTION OF PROTEINS Total daily protein load: a, 70-100 g of dietary proteins b, 35-200 g of endogenous proteins (from digestive enzymes and dead cells) Digestion of proteins: Denaturation: low pH in the stomach Digestion (proteolysis): Proteinases (endopeptidases) Peptidases (exopeptidases) carboxypeptidases aminopeptidases

5. DIGESTION AND ABSORPTION OF PROTEINS LUMEN LUMINAL SURFACE ENTEROCYTES Na+ Free amino Amino acids acids (40%) Oligopeptides Dipeptides (60%) Tripeptides Na+ Polypeptides H+ Amino acids pepsin H+ dipeptidase tripeptidase trypsin chymotrypsin elastase carboxypeptidase A + B endopeptidase aminopeptidase dipeptidase

7. All Proteinases are synthetized as inactive pro-enzymes (zymogens) A, Gastric juice: has low pH to kill microorgnisms and to denature proteins. pepsinogenpepsin + 42 aa long peptide (limited proteolysis) B, Pancreatic juice is rich in the following proenzymes: Trypsinogen, Chymotrypsinigen Pro-elastase They are activated in the small intestine (duodenum) Pro-carboxypeptidase: synthetized by the pancreas, activated in the small intestine Aminopeptidases: secreted by the absorptive cells of small intestine

10. ACTIVATION OF TRYPSIN Intestinal endocrine cell Oligopeptides amino acids (from stomach, digested by pepsin) CCK (cholecystokinin) CCK and secretin Intestinal mucosal epithelial cell Pancreatic acinar cell enteropeptidase Trypsinogen trypsin Chymotrypsinogen Chymotripsin Proelastase Elastase Procarboxypeptidase Carboxypeptidase

12. DIGESTION AND ABSORPTION OF PROTEINS LUMEN LUMINAL SURFACE ENTEROCYTES Na+ Free amino Amino acids acids (40%) Oligopeptides Dipeptides (60%) Tripeptides Na+ Polypeptides H+ Amino acids pepsin H+ dipeptidase tripeptidase trypsin chymotrypsin elastase carboxypeptidase A + B endopeptidase aminopeptidase dipeptidase

13. BRUSH BORDER SPECIFIC TRANSPORT SYSTEMS 1, for neutral amino acids with short or polar side chains (e.g. Ser, Thr, Ala) 2, for neutral amino acids with aromatic or hydrophobic side chains (e.g. Phe, Tyr, Val, Met) 3, for imino acids (Pro, Hyp) 4, for -amino acids (-Ala, taurine) 5, for basic amino acids and cystine (Arg, Lys, Cys-Cys) 6, for acidic amino acids (Asp, Glu) 7, for dipeptides

21. COMPLETE AND NON-COMPLETE PROTEINS IN THE FOOD 1, Complete proteins: animal proteins, such as milk, fish, meat, egg + soya-bean, mushroom They contain all essential amino acids. 2, Non-complete proteins: many food derived from plants, such as grains (wheat, maize, rice. etc.) They generally lack triptophan and lysine. Diet based on grains and not supplemented by complete proteins resuts in dramatic deficiency states in children! Vegetarian diets: two or more proteins should be consumed together! For example, if corn (which is deficient in lysine) is combined with legumes (deficient in methionine but rich in lysine), the efficiency of utilization approaches that of animal protein.

22. NUTRITIONAL REQUIREMENTS 1, Quantitative requirements a, recommended protein intake: 0.8 g/kg (body weight) per day higher requirements for children, in pregnancy, in reconvalescence b, Nitrogen balance: difference between the total nitrogen intake and the total excreted nitrogen c, excess amino acids are not stored (in contrast to carbohydrate and lipid metabolism) (muscle protein may serve as a store in starvation) d, ‘protein sparing’: if we eat enough carbohydrate and fats for energy generation, the need for protein decreases 2, Qualitative requirements a, human body is unable to synthetize the carbon skeleton of a number of amino acids, these are called ‘nutritionally essential amino acids’ b, semiessential amino acids: arginine: may be produced by the urea cycle histidine: may be produced by intestinal bacteria

24. PROTEIN-ENERGY MALNUTRITION Mostly in developing countries MARASMUS: inadequate intake of both protein and energy The marasmic infants will have a thin, wasted appearance KWASHIORKOR: inadequate intake of protein with adequate energy intake In kwashiorkor the child will often have a deceptively plump appearance due to edema. Diminished immune response!

25. METABOLISM OF AMINO ACIDS Role of amino acids: 1, Constituent of proteins protein turnover: 1-2% of total body protein per day half life of proteins: 30 min - 150 hours or more 2, Precursors of other biologically active molecules 3, Sources of energy: carbon skeleton 3C or 4C intermediates acetyl-CoA

26. SOURCE OF AMINO ACIDS 1, Dietary proteins 2, ‘nutritionally non-essential’ amino acids synthetized by the human body Dietary proteins Amino acids de novo synthetized amino acids Body proteins NH3 urea Neurotransmitters Phospholipids Porphyrins Purines Pyrimidines Other compounds Acetyl-CoA Carbohydrate intermediates glucose Fatty acids CO2+ Steroids H2O

28. DEGRADATION OF INTRACELLULAR PROTEINS Protein degradation pathways operate in different cytoplasmic compartments, proteins coming from endocytosis are degraded in the lysosomes, by lysosomal proteases. Most proteins degraded in the cytosol are broken down by proteosomes. - those proteins whose life time must be short - those proteins which are damaged or misfolded (containing oxidized or otherwise abnormal amino acids. etc.) Inorder to be degraded by proteosomes, proteins are marked by ubiquitin. Ubiquitin is a small protein which is attached covalently to selected proteins by specific enzymes. (short amino acid sequences are recognized by these enzymes which add one or more ubiquitin molecules to the protein.) ATP is required for the activation of ubiquitin. The process is called: ATP- and ubiquitin-dependent protein degradation

31. OTHER PROTEASES WORKING INSIDE THE CELL These proteases are parts of regulatory processes: Calcium-dependent proteases: Calpains Program cell death, apoptosis requires the activation of specific protease: Caspases