Digestion And Catabolism Of Proteins And Amino Acids PDF

Digesti on a n d C at ab ol i s m of proteins a n d Ami no Acids P R E S E N TAT I O N Dr. Ula Ab ba s Ze ki Objectives of this lecture : Illustrate the digestion and absorption processes of the protein and A.A understand the Catabolismof amino acids includingamino...

Digesti on a n d C at ab ol i s m of proteins a n d Ami no Acids P R E S E N TAT I O N Dr. Ula Ab ba s Ze ki Objectives of this lecture : Illustrate the digestion and absorption processes of the protein and A.A understand the Catabolismof amino acids includingamino acids pool and steps of α amino group metabolism Explain diagnostic importance of aminotransferase enzymes ILO:K3, S12, A0  Amino acids are the basic structural units of peptides and proteins playvariable roles in: provision of energy formation of a number of important biomolecules, includinghormones, neurotransmitters, and signaling molecules.  Unlike fats and carbohydrates, the body doesn’t store amino acids. So ,amino acids mustbe obtained either from diet,synthesized denovo, orproducedfromthedegradationof bodyprotein. Anyexcess more than the biosynthetic needs will be rapidly degraded.  DIETARY PROTEIN DIGESTION Proteins are generally too large to be absorbed by the intestine, therefore, proteins must be hydrolyzed to yield di- and tripeptides as well as individual amino acids to be absorbed. Proteolytic enzymes responsible for degrading proteins are produced by three different organs: stomach, pancreas, andthe small intestine  A. Digestionbygastricsecretion The digestion of proteins begins in the stomach, which secretes gastric ýuicecontaining hydrochloric acid (HCl)and the proenzyme pepsinogen. HCl: stomach HCL is too dilute (pH 2–3) to hydrolyze proteins. secreted by the parietal cells of the stomach, its functions is kill somebacteria and to denature proteins, thereby making them more susceptible for subsequent hydrolysis by proteases. Pepsin:This acid-stable endopeptidase is secreted by the chief cells of the stomach as an inactive zymogen (or proenzyme), pepsinogen. In the presence of HCl, pepsinogen undergoes a conformational change and cleave itself to the active form (pepsin),which releases polypeptides and a few free amino acids from dietary proteins.  B. Digestion by pancreatic enzymes Onentering the small intestine, the polypeptides produced in the stomach by the action of pepsin will be further cleaved to oligopeptides and amino acids by a group of pancreatic proteases that include both endopeptidases and exopeptidases. These enzymes are synthesized and secreted as inactive zymogens Their release and activation are mediated by the secretion of cholecystokinin,a polypeptide hormone of the small intestine.  Zymogenactivation: Enteropeptidase (enterokinase), present on the luminal surface of the enterocytes of the brush border, converts the pancreatic zymogentrypsinogen to trypsin. Trypsinsubsequently converts other trypsinogen molecules to trypsin. Thus, enteropeptidase unleashes a cascade of proteolytic activity , and trypsin is the commonactivator of all the pancreatic zymogens  Digestion abnormalities deficiency in pancreatic secretion (chronicpancreatitis,cysticfibrosis,orsurgical removalof pancreas),lead to incomplete digestion and absorption of fat and protein>>>> abnormal appearance of lipids in the feces (steatorrhea) & undigested protein. Celiacdiseaseis a malabsorption disease resulting from immune-mediated damage to the small intestine in response to ingestion of gluten (or gliadin produced from gluten), a protein found in wheat, barley, and rye.  C.Digestion of oligopeptides by small intestine enzymes The luminal surface of the enterocytes contains aminopeptidase, which repeatedly cleaves the N-terminal residue from oligopeptides to produce even smaller peptides and free amino acids.  D. Amino acid and small peptide intestinal absorption Most free amino acids are taken into enterocytes by sodiumdependentsecondaryactive transportmechanism Di- and tripeptides, however, are taken upby a proton-linkedpeptidetransporter(PepT1). The peptides are then hydrolyzed to free amino acids, which are released from enterocytes into the portal system. These amino acids are either metabolized by the liver or released into the general circulation. Branched-chain amino acids (BCAA) are notmetabolized by the liver but, instead, are sent fromthe liver to musclevia the blood.  Absorption abnormalities The smallintestineandtheproximaltubulesof thekidneys have common transport systems for amino acid uptake. Anydefect in one of these systems results in an inability to absorb particular amino acids into the intestine and into the kidney tubules. Anexample for that is Cystinuria C a t a b o l i sm of Amino Acids  OVERALL NITROGEN METABOLISM A.A catabolism is part of the larger process of the metabolism of nitrogen-containingmolecules. N enters the body in a variety of compounds present in food and leaves as urea, ammonia, and other products derived from amino acid metabolism. The role of body proteins in these transformations involves two important concepts: the amino acid pool and protein turnover  The a mi no a cid The amin o aci d pool i s po o l s u p p li e d b y de pl et ed b y 1)bythedegradationof endogenous 1) synthesisof bodyprotein (body)proteins, most of whichare 2)consumptionof aminoacidsas reutilized precursorsof essential nitrogen- 2)aminoacidsderivedfrom containingsmall molecules exogenous(dietary)protein 3)conversion of amino acids to glucose, 3)nonessential aminoacids glycogen, fattyacids, and ketone bodies or synthesizedfromsimple oxidationtoCO2+ H2O intermediatesof metabolism B. Protein turnover proteins are constantly synthesized and degraded (turned over), permit removal of abnormal or unneeded proteins. total amount of protein remains constant because the rate of protein synthesis is sufficient to replace the protein that is degraded.  A.A catabolism first phase : secondphase: removal of the α-amino groups to form ammonia & carbon skeletons of the α-keto acids are converted to correspondingα-keto acids, which the carbon intermediates of that can be metabolized to carbon dio skeletons of amino acids. (CO2)and water (H2O), glucose, fatty acids, or ketone bod part of the free ammonia is excreted in urine, but by the central pathways of metabolism. most is used inthe synthesis of urea  01 NITROGEN REMOVAL FROM AMINO ACIDS  The presence of theα-aminogroup keeps amino acids safely locked away from oxidative breakdown so removing this group is essential for producing energyfrom any amino acid and it is an obligatorystepinthe catabolismof all a. a. Once removed, this nitrogen can be incorporated into other compounds or excreted as urea, and then the carbon skeletons being metabolized.  1.Transamination transfer of an amino group from an alpha-AA to an alpha-keto acid , which is an AA with an alpha-keto group (=O) to produce an α-keto acid and glutamate. The original AA loses an amino group and gains a keto group, becoming an alpha- keto acid, while the original alpha-keto acid loses its keto group and gains an amino, becoming a nonessential AA (glutamate). Glutamate  The reaction is catalyzed by aminotransferaseenzymesthat found in high concentrations in liver andrequirescoenzymepyridoxalphosphate. Glutamate produced by transamination can be oxidativelydeaminatedor used as anaminogroup donorin the synthesis of nonessential aminoacids. Allaminoacids,with the exception of lysineandthreonine participate in transamination. Twoimportantaminotransferaseenzymesarealanineaminotransferase(ALT) andaspartate aminotransferase(AST). ALT is present in manytissues mainly liver, also in kidney, skeletal muscle and heart. ALT transfers an amino group from alanine to alpha-ketoglutarate, forming pyruvate and glutamate. AST present in the heart, skeletal muscle, liver, kidney and RBC. AST transfers an amino group from aspartate to alpha- ketoglutarate, forming oxaloacetate and glutamate. Diagnosticvalueof Aminotransferases These enzymes are normally intracellular, and low levels that found in plasma represent the release of cellular contents during normal cell turnover. Elevated plasma levels indicate damage to cells rich in these enzymes. For example, physical trauma or a disease process can cause cell lysis, resulting in release of intracellular enzymes into the blood. AST and ALT, are of particular diagnostic value when they are found elevated in the plasma. a. He patic d i s e a s e b. No nhe patic disease: elevated in nearly all hepatic diseases Aminotransferases maybe elevated but are particularlyhigh in in nonhepatic diseases such as conditions that cause extensive cell those that cause damageto necrosis, such as severe viral cardiac or skeletal muscle. hepatitis, toxic inýury.  2. Oxidativedeamination: Amino group removal. process through which amino groups are removed from AAs, releasing free cytotoxic ammonia: ammonia →ammonium→urea via the urea cycle inthe liver. Result of this reaction is α-keto acids that can enter the central pathways of energy metabolism and ammonia, which is a source of nitrogen in hepatic urea synthesis.  Oxidative deamination by glutamate dehydrogenase. Glutamate,thatresulted fromthetransamination, isuniquein that it isthe only aminoacidthat undergoesrapidoxidativedeamination,areaction catalyzedby glutamatedehydrogenase[GDH] enzyme.  GDH, a mitochondrial enzyme, is unusual in that it can use either nicotinamideadeninedinucleotide (NAD⁺) orits phosphorylatedreduced form(NADPH) asacoenzyme. The sequential action of transamination and the oxidative deamination of that glutamate (regenerating α-ketoglutarate) will provide a pathway by which the amino groups of most amino acids can be released as ammonia.  Nonoxidative deamination Certain a.a ex. serine , threonine, & cysteine are deaminated by specific lyases that require pyridoxal phosphate.  1.transamination A.A Glutamate + α keto acid 2.oxidative deamination NH3 + α keto acid 3.Go to the liver (Urea Cycle) Urea