Transcript Chapter 1
Chapter 6 Protein 2009 Cengage-Wadsworth Functional Categories • Catalysts - enzymes – Hydrolases - cleave compounds – Isomerases - transfer atoms in a molecule – Ligases (synthases) - join compounds – Oxidoreductases - transfer electrons – Transferases - move functional groups 2009 Cengage-Wadsworth Functional Categories • Messengers – Hormones • Structural elements – Contractile proteins – Fibrous proteins – Globular proteins • Immunoprotectors – Immunoproteins (antibodies) 2009 Cengage-Wadsworth Functional Categories • Transporters – Albumin – Transthyretin (prealbumin) – Transferrin – Ceruloplasmin – Lipoproteins 2009 Cengage-Wadsworth Functional Categories • Buffers – Regulation of acid-base balance • Fluid balancers – Proteins attract water to blood • Other roles – Adhesion, signaling, receptors, storage – Conjugated proteins • Glycoproteins • Proteoglycans 2009 Cengage-Wadsworth Protein Structure & Organization • Primary structure – Sequence of covalent bonds among amino acids • Secondary structure – Hydrogen bonding – -helix – -conformation or -pleated sheet – Random coil 2009 Cengage-Wadsworth Protein Structure & Organization • Tertiary structure – Clustering of hydrophobic AAs toward center – Electrostatic (ionic) attraction – Strong covalent bonding between cysteine residues - disulfide bridges • Quaternary structure – Interactions between 2 or more polypeptide chains – Oligomers 2009 Cengage-Wadsworth Amino Acid Classification • Structure – Central C – At least 1 amino group (NH2) – At least 1 carboxy (acid) group (COOH) – Side chain (R group) • Makes AA unique 2009 Cengage-Wadsworth Amino Acid Classification • Net electrical charge – Zwitterions have none • Polarity – Polar or nonpolar – Determined by R group • Essentiality – Lysine, threonine & histidine totally indispensable 2009 Cengage-Wadsworth Sources of Protein • Exogenous sources – Animal products - except fats – Plant products - grains/grain products, legumes, vegetables • Endogenous proteins – Desquamated mucoasal cells – Digestive enzymes & glycoproteins 2009 Cengage-Wadsworth Digestion & Absorption • Protein digestion – Mouth & esophagus - none – Stomach • HCl denatures • Pepsin hydrolyzes peptide bonds 2009 Cengage-Wadsworth Digestion & Absorption – Small intestine • Pancreatic enzymes – – – – – Trypsinogen trypsin Chymotrypsinogen chymotrypsin Procarboxypeptidases A & B carboxypeptidases Proelastase Collagenase • Brush border peptidases – Aminopeptidases, dipeptdylaminopeptidases, tripeptidases • Tripeptides hydrolyzed or absorbed at brush border 2009 Cengage-Wadsworth Digestion & Absorption • Intestinal brush border membrane amino acid & peptide absorption – Amino acid transport • Carriers required - passive & active transporters – Peptide transport • PEPT1 • Co-movement of protons (H+) 2009 Cengage-Wadsworth Digestion & Absorption • Intestinal basolateral membrane transport of amino acids – Diffusion & sodium-independent transport are main modes • Intestinal cell amino acid use – Cells use or partially metabolize for release into blood 2009 Cengage-Wadsworth Digestion & Absorption – Intestinal glutamine metabolism • Primary energy source for enterocytes – Intestinal glutamate metabolism – Intestinal aspartame metabolism – Intestinal arginine metabolism – Intestinal methionine & cysteine metabolism 2009 Cengage-Wadsworth Digestion & Absorption • Amino acid absorption into extraintestinal tissues – AAs enter portal vein to liver – Transport into hepatocytes – Transport into other cells – -glutamyl cycle 2009 Cengage-Wadsworth Amino Acid Metabolism • Metabolism of AAs includes: – Protein synthesis – Amino acid catabolism – Hepatic catabolism • Uses • Uses • Uses • Uses of of of of aromatic amino acids sulfur-containing amino acids branched-chain amino acids other amino acids – Plasma amino acids & pools 2009 Cengage-Wadsworth Synthesis of Plasma Proteins, NitrogenContaining Nonprotein Compounds, & Purine & Pyrimidine Bases • Plasma proteins – – – – – – – – Albumin Transthyretin (prealbumin) Retinol-binding protein Blood clotting proteins Immunoproteins Transport proteins Acute phase proteins Stress (heat) shock proteins (hsp) 2009 Cengage-Wadsworth Synthesis of Plasma Proteins, NitrogenContaining Nonprotein Compounds, & Purine & Pyrimidine Bases • Nitrogen-containing nonprotein compounds – Glutathione - antioxidant, reacts with H2O2, AA transport, conversion of prostaglandin H2 to D2 & E2 – Carnitine - FA transport – Creatine - part of phosphocreatine (high-energy compound) 2009 Cengage-Wadsworth Synthesis of Plasma Proteins, NitrogenContaining Nonprotein Compounds, & Purine & Pyrimidine Bases – Carnosine - may be antioxidant – Choline - methyl donor, part of acetylcholine & lecithin & sphingomyelin 2009 Cengage-Wadsworth Synthesis of Plasma Proteins, NitrogenContaining Nonprotein Compounds, & Purine & Pyrimidine Bases • Purine & pyrimidine bases – Main constituents of DNA & RNA – Pyrimidines • 6-membered rings containing N in positions 1 & 3 • Uracil, cytosine & thymidine – Purines • 2 fused rings, N in positions 1, 3, 7, 9 • Adenine & guanine 2009 Cengage-Wadsworth Protein Synthesis Overview • Insulin & glucagon • Rate of protein digestion • Leucine • Fed vs. fasted state 2009 Cengage-Wadsworth Amino Acid Catabolism Overview • Transamination &/or deamination of amino acids – Deamination = removal of amino group – Transamination = transfer of amino group from one AA to AA carbon skeleton or -keto acid • Catalyzed by aminotransferases 2009 Cengage-Wadsworth Amino Acid Catabolism Overview • Disposal of ammonia--the urea cycle – NH3 combines with CO2 or HCO3- to form carbamoyl phosphate – Carbamoyl phosphate reacts with ornithine transcarbamoylase (OTC) to form citruline – Aspartate reacts with citruline to form argininosuccinate – Arginosuccinate is cleaved to form fumarate & arginine – Urea is formed and ornithine is re-formed from cleavage of arginine 2009 Cengage-Wadsworth Amino Acid Catabolism Overview • An overview of metabolism of the carbon skeleton/-keto acid – – – – Energy generation Glucose & ketone body production Cholesterol production Fatty acid production 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Aromatic Amino Acids • Phenylalanine & tyrosine – Phenylalanine converted to tyrosine by phenylalanine hydroxylase – Tyrosine • Degradation begins with transamination to phydroxyphenylpyruvate • Tyrosine used in other tissues for synthesis of Ldopa & catecholamines • Melanin, thyroid hormones – Disorders of phenylalanine & tyrosine metabolism 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Aromatic Amino Acids • Tryptophan – Catabolized to N-formylkynurenine – This is catabolized to formate & kynurenine – Used for: • Protein synthesis • Energy, glucose, & ketone body production • Synthesis of serotonin & melatonin – Disorders of tryptophan metabolism. 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Sulfur (S)-Containing Amino Acids • Methionine – Converted to S-adenosyl methionine • SAM is principal methyl donor • Removal of methyl group yields S-adenosyl homocysteine (SAH) – SAH converted to homocysteine – Homocysteine reacts with serine to form cystathionine – Cystathionine cleaved to form cysteine & ketobutyrate – Propionyl CoA (made from -ketobutyrate) converted to D-methylmalonyl CoA – Disorders of methionine metabolism 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Sulfur (S)-Containing Amino Acids • Cysteine – Used for protein & glutathione synthesis – Converted to cysteine sulfinate, used to produce taurine – Taurine important in retina, functions as bile salt & inhibitory neurotransmitter – Cysteine degradation yields pyruvate & sulfite 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of the Branched-Chain Amino Acids • Isoleucine, leucine, & valine • Taken up & transaminated primarily in muscles 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Other Amino Acids • Lysine – Ketogenic - catabolism yields acetyl CoA – Disorders of lysine metabolism • Threonine – 3 pathways – Disorders of threonine metabolism 2009 Cengage-Wadsworth Hepatic Catabolism & Uses of Other Amino Acids • Glycine & serine – Produced from one another in reversible reaction requiring folate – Disorders of glycine metabolism • Arginine – Kidney - creatine synthesis – Liver - generation of urea & ornithine • Histidine – Glutamate, carnosine, histamine 2009 Cengage-Wadsworth Amino Acids Not Taken Up by the Liver: Plasma Amino Acids & Amino Acid Pool(s) • Plasma concentrations rise after a meal • Pool of about 150 g of endogenous + exogenous AAs • Re-use thought to be primary source of AAs for protein synthesis • More nonessential than essential in pool 2009 Cengage-Wadsworth Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism • Glutamine & the liver, kidneys, & intestine – Ammonia transport – Hypercatabolic conditions • Alanine & the liver & muscle – Inter-tissue transfer of amino groups – Liver: converted to glutamate or glucose 2009 Cengage-Wadsworth Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism • Skeletal muscle – Isoleucine, leucine, & valine – Nitrogen-containing compounds as indicators of muscle mass & muscle/ protein catabolism 2009 Cengage-Wadsworth Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism • Kidneys – Serine synthesis from glycine – Glycine catabolism to ammonia – Histidine generation from carnosine degradation – Arginine synthesis from citruline – Tyrosine synthesis from phenylalanine – Guanidoacetate formation from arginine & glycine for creatine synthesis 2009 Cengage-Wadsworth Brain & Accessory Tissues • Biogenic amines & neurotransmitters/hormones – Tryptophan - melatonin & serotonin – Tyrosine - dopamine, norepinephrine, epinephrine – Glysine - inhibitory neurotransmitter – Taurine - inhibitory neurotransmitter – Aspartate - excitatory neurotransmitter – Glutamate - excitatory neurotransmitter or converted to -amino butyric acid (GABA) 2009 Cengage-Wadsworth Brain & Accessory Tissues • Neuropeptides – Hormone-releasing factors – Endocrine effects – Modulatory actions on transmitter functions, mood or behavior – Neurosecretory cells of hypothalamus secrete – Synthesized from AAs via DNA codes 2009 Cengage-Wadsworth Protein Turnover: Synthesis & Catabolism of Tissue Proteins • Food intake & nutritional status • Hormonal mediation • AA pools connect 2 cycles of N metabolism: – Protein turnover – Nitrogen balance • Protein synthesis & degradation controlled separately 2009 Cengage-Wadsworth Protein Turnover: Synthesis & Catabolism of Tissue Proteins • Cellular protein degradation systems – Lysosomal degradation – Proteasomal degradation – Calcium or calcium-activated proteolytic degradation 2009 Cengage-Wadsworth Changes in Body Mass with Age • Lean body mass increases throughout childhood – Changes in total fluid & ECF/ICF • Gender differences develop during adolescence – Greater increase in males • After 25, weight gain = fat gain • Lean mass decreases with increasing age – More so in women than men – Body water declines too 2009 Cengage-Wadsworth Protein Quality & Protein Intake • Foods can be categorized as: – High-quality or complete proteins – Low-quality or incomplete proteins • Evaluation of protein quality – Nitrogen balance/nitrogen status – Chemical or amino acid score – Protein digestibility corrected amino acid score 2009 Cengage-Wadsworth Protein Quality & Protein Intake – Protein efficiency ratio – Biological value – Net protein utilization – Net dietary protein calories percentage • Protein information on food labels – % Daily Value 2009 Cengage-Wadsworth Protein Quality & Protein Intake • Recommended protein & amino acid intakes – RDA for adults = 0.8 g/kg – AI for birth-6 months – RDA for indispensible AAs – Negative effects of high protein intakes controversial (no UL) – AMDR = 10%-35% kcal 2009 Cengage-Wadsworth Protein Quality & Protein Intake • Protein deficiency/malnutrition – Kwashiorkor • Adequate energy with insufficient protein • Edema owing to loss of blood proteins – Marasmus • Wasting, emaciation • Chronic insufficiency of energy & protein 2009 Cengage-Wadsworth Perspective 6 Protein Turnover: Starvation Compared with Stress 2009 Cengage-Wadsworth Starvation vs. Stress • Starvation – Protein synthesis decreases – Hormone balance adjusts – Adaptation - muscle catabolism slows • Stress – – – – Hypermetabolism Lipolysis doesn’t lead to ketosis Muscle catabolism undiminished Protein turnover - immune response & acute phase response 2009 Cengage-Wadsworth