Amino Acid Metabolism Protein metabolism xiaoli
synthesis metabolism catabolism Reviews:
Digestion and absorption of protein • Normal metabolism of amino acids • Special products of amino acids Major content
Nutritional Function of Protein Proteins play a major role in ensuring your health well being. There are innumerable functions of proteins in the body. • building and repairing of body tissues. protein makes up nearly 17 percent of the total body weight. For example: muscle contains about 1/3 protein, bone about 1/5 part and skin consists of 1/10 portion. The rest part of proteins is in the other body tissues and fluids. • Take part in some kinds of important physiological activities regulation of body processes and formation of enzymes and hormones, antibody.There are distinctive kinds of proteins, each performing a unique function in the body. • Oxidation and supply energy
How to assess the condition of protein metabolism? 1. Nitrogen balance the balance between the amount of nitrogen taken in (foods or the body) and the amount given off (lost or excreted) Significance: Measuring the amount of intake and losses of total nitrogen can help us to know the general situation of protein metabolism.
nitrogen balance ★ positive: synthesis > degradation (e.g., growth, body building) ★negative: synthesis < degradation (e.g., starvation, trauma, cancer cachexia) ★Equilibrium: synthesis = degradation (healthy adults eating a balanced diet)
2. Physical requirements of proteins • Lowest requirement: 30~50g/day • Recommend requirement: 80g/day (65kg man) Some sources of dietary protein include: Meat, poultry and fish Eggs, Dairy products Seeds and nuts Beans and lentils Soy products Grains, especially wheat and rice, barley and corn. Amino acids are not stored by the body, must be obtained from the diet, synthesized de novo.
3. Nutrition value of proteins (1) Essential amino acids : Eight amino acids are generally regarded as essential for humans: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, and lysine some Amino acids that cannot be synthesized by the body and must be obtained from the diet.
(2) Non- essential amino acids other 12 kinds of AAs,the non-essential or dispensable amino acids can be synthesized in the body either other roadways. Note: a Arg is synthesized in the urea cycle, but the rate is too slow to meet the needs of growth in children b Met is required to produce cysteine if the latter is not supplied adequately by the diet. c Phe is needed in larger amounts to form tyr if the latter is not supplied by the diet. His and Arg are essential AAs for infants and children.
(4) nutrition value A protein’s nutritional value is judged by how many of the essential amino acids it provides and in what quantity. Different foods contain different numbers and amounts of the essentialamino acids. lysine tryptophan
(5) Complementary effect of dietary proteins • Two or more plant proteins are consumed together which complement each other in essential amino acid content.
Amino acids hydrolysis absorb Dietary protein 2.1 Digestion Significance: ◆ Large small Help to absorb ◆ eliminatethe species specificity andantigenicity, avoid allergy , toxic reaction.
site: stomach, small intestine Pepsin Chymotrypsin, trypsin, and exopeptidases Proteolytic enzymes of pancreatic juice Amino acids
HCl Pepsinogen Pepsin Aromatic amino acids • Initiated in stomach • enzymes: pepsin HCl from parietal cells • Stomach pH 1.6 to 3.2 • Pepsinogen from chief cells • The substrate mainly are phenylalanine,tyrosine,tryptophan • Products: insoluble protein, soluble protein, polypeptides and amino acids
Trypsinogen Chymotrypsinogen procarboxypeptidase Proelastase trypsin Chymotrypsin Carboxypeptidase elastase Zymogens • Pancreatic enzymes secreted Zymogens A zymogen is the inactive precursor of an enzyme. Activation of zymogen A inactive zymogen become active enzyme. In a zymogen, a peptide blocks the active site of the enzyme. Cleaving off this peptide activates the enzyme.
Significance: 1. avoids self-digestion: This is necessary to prevent the digestive enzymes from autodigesting the cells that produce them. 2. stored and transported safely : The body typically secretes zymogens rather than active enzymes because they can be stored and transported safely without harm to surrounding tissues, and released when conditions are favorable for optimal activity.
protease active site In a zymogen, a peptide blocks the active site of the enzyme. Cleaving off this peptide activates the enzyme. The molecule is composed of amino acids strung together into a peptide. When the zymogen is in the presence of protease, some of the amino acids are removed. This cleavage renders the zymogen a functional enzyme by changing the shape of the peptide and forming the active site where enzymatic action will occur.
enterokinase trypsinogen trypsin chymotrypsinogen chymotrypsin proelastase elastase procarboxypeptidase carboxypeptidase cascade reaction Amplification effect
Proteolytic enzymes of pancreatic juice Protein Digestion –Small Intestine trypsin: Arg, Lys (C) chymotrypsin: Tyr, Trp, Phe, Met, Leu (C) endopeptidases elastase: Ala, Gly, Ser (C) carboxypeptidase exopeptidases aminopeptidase
Protein Digestion • Proteins are broken down to • Tripeptides • Dipeptides • Free amino acids 2.2 absorption
Free amino acids Absorption ★Carrier systems ★Meister cycle/ γ-glutamyl cycle transport amino acids
Amino acids carrier protein Amino acids Amino acids Na+ Na+ Na+ ATP Free Amino Acid Absorption Lumen (small intestine) • Carrier systems • Neutral AA • Basic AA • Acidic AA • Amino acids Na+ pump • Entrance of some AA is via active transport • Requires energy Brush broad membrance
Meister cycle/ γ-glutamyl cycle transport amino acids γ-glutamyl cycle include two steps： • GSH(glutathione) transport amino acids • GSH synthesis
extracellular intracellular AA γ-glutamylcyclotransferase Cys-Gly peptase 5-pidolic acid ATP 5-oxoproline AA glycine cysteine ADP+Pi GSH glutamic γ-glutamylcysteine synthetase(γ-GCS) ATP glutathione synthetase ADP+Pi γ-glutamylcysteine ADP+Pi ATP Cell membrance γ-glutamyl amino acid γ-glutamyl transferase γ-glutamyl cycle / Meister cycle 目 录
Peptide Absorption • Form in which the majority of protein is absorbed • More rapid than absorption of free amino acids • Active transport • Energy required • Metabolized into free amino acids in enterocyte • Only free amino acids absorbed into blood
§2.3Putrefaction of proteins Putrefaction of proteins: Some undigested proteins and no absorbed products are anaerobic decomposed by the bacteria in intestine. The products are toxic to body except few vitamin and fatty acid.
histidine histamine tryptamine tryptophan β-hydroxytyramine CO2+H2O tyromine tyrosine liver phenolethanolamine phenylalanine phenylethylamine CO2+H2O liver 1. Production of amines
phenolethanolamine phenylethylamine tyramine β-hydroxytyramine noradrenalin dopamine hydroxylase hydroxylase
phenolethanolamine noradrenalin β-hydroxytyramine dopamine • false neurotransmitter is a chemical compound which closely imitatesthe action of a neurotransmitter in the nervous system,but that has no or little effect on postsynaptic receptors.
3. Some other toxic materials 2. Production of ammonia (NH3) • Two sources: (1) Metabolism on unabsorbed amino acids (2) Urea hydrolyzed by urease • Tyr → phenol • Trp → indole • Cys → hydrogen sulfide (H2S)
§ 3.1 Protein turnover the balance between protein synthesis and protein degradation . • In healthy adults, the total amount of protein in the body remains constant, because the rate of protein synthesis is just sufficient to replace the protein that is degraded. this process is called protein turnover. • Rapid protein turnoverensures that some regulatory proteins are degraded so that the cell can respond to constantly changingconditions.
half-life Half-life is the period of time it takes for a substance undergoing decay to decrease by half. Examples of protein turnover in the body
§ 3.2 Degradation of protein in cells 1. Lysosomal pathway • Extracellular proteins, membrane-associated proteins and long-lived proteins • ATP-independent process • Enzyme: Cathepsins
2. Cytosol pathway • Abnormal proteins, damaged proteins and short-lived proteins ATP ubiquitin enzyme ubiquitination ubiquitin-proteins Proteasome 7~9 residues peptides
ubiquitin ubiquitious • Ubiquitin (Ub) is a small protein that is composed of 76 amino acids; exists in all eukaryotic cells, only in eukaryotic organisms. • Among eukaryotes, ubiquitin is highly conserved, meaning that the amino acid sequence does not differ much when very different organisms are compared. For example, there are only 3 differences in the sequence when Ub from yeast is compared to human Ub.
Ubiquitin performs its myriad functions through conjugation to a large range of target proteins.
ATP AMP+Pi E1 ubiquit -E1 ubiquitin + E1 E2 ubiquitin-E1 ubiquitin-E2 ubiquitination Activate ubiquitin 1. E1 enzymes known as Ub-activating enzymes. These enzymes modify Ub so that it is in a reactive state (making it likely that the C-terminal glycine on Ub will react with the lysine side-chains on the substrate protein). Ub-conjugating enzymes 2. E2 enzymes known as Ub-conjugating enzymes. These enzymes actually catalyze the attachment of Ub to the substrate protein
proteasome pro Degratation(7~9 residues peptides) Ubiquitin-pro E2 E3 Ubiquitin-pro ubiquitin-E2 Ub-ligases 3. E3 enzymes known as Ub-ligases. E3's usually function in concert with E2 enzymes, but they are thought to play a role in recognizing the subtrate protein.
The general reaction pathway is shown in the figure below. First, Ub is activated by E1 in an ATP-dependent fashion. E2 and E3 then work together to recognize the substrate protein and conjugate Ub to it. Ub can be attached as a monomer or as a previously synthesized chain (as shown). From this point, the ubiquinated protein is shuttled to the proteasome for degradation
Amino acid pool: amino acids in intracellular and extracellular fluids.
N H U r e a 3 D i e t a r y a b s p r o t e i n s o n r o K e t o n e b o d i e s i p t a t i n i o m n a e d α - K e t o a c i d O x i d a t i o n d e g r a d a t i o n T i s s u e A m i n o a c i d p r o t e i n s m e t a b o l i c p o o l s y n t h e s i s d e G l u c o s e c a r b o x y l A m i n o a c i d s a c o n v e r s i o n t i o n s y n t h e s i z e d A m i n e N o n - p r o t e i n n i t r o g e n C O 2 c o m p o u n d s § 3.1 The sources and fates of AAs Sources of amino acids Fates of amino acids Synthesis of proteins
§ 3.3 The catabolism of AAs 1. Deamination of AAs Four types: transamination oxidative deamination non-oxidative deamination union deamination
(1) Transamination aminotransferase Transamination is the process by which an amino group, usually from glutamate, is transferred to an α-keto acid, with formation of the corresponding amino acid plus α-ketoglutarate.
Key points: ① reversible:Transaminases (aminotransferases) catalyze the reversible reaction at right. ② Lys and Pro cannot be transaminated. ③Aminotransferases utilize a coenzyme - pyridoxal phosphate - which is derived from vitamin B6.
The prosthetic group of Transaminase is pyridoxal phosphate (PLP), a derivative of vitamin B6.