2009 cengage-wadsworth chapter 6 protein. 2009 cengage-wadsworth functional categories catalysts -...

2009 Cengage-Wadsworth

Chapter 6

Protein


Functional Categories

• Catalysts - enzymes– Hydrolases - cleave compounds– Isomerases - transfer atoms in a

molecule– Ligases (synthases) - join compounds– Oxidoreductases - transfer electrons– Transferases - move functional

groups



• Messengers – Hormones

• Structural elements– Contractile proteins– Fibrous proteins– Globular proteins

• Immunoprotectors– Immunoproteins (antibodies)



• Transporters– Albumin– Transthyretin (prealbumin)– Transferrin– Ceruloplasmin– Lipoproteins



• Buffers– Regulation of acid-base balance

• Fluid balancers– Proteins attract water to blood

• Other roles– Adhesion, signaling, receptors, storage– Conjugated proteins

• Glycoproteins• Proteoglycans


Protein Structure & Organization

• Primary structure– Sequence of covalent bonds among

amino acids• Secondary structure

– Hydrogen bonding -helix -conformation or -pleated sheet– Random coil


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


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


Amino Acid Classification

• Net electrical charge– Zwitterions have none

• Polarity– Polar or nonpolar– Determined by R group

• Essentiality– Lysine, threonine & histidine totally

indispensable


Sources of Protein

• Exogenous sources– Animal products - except fats– Plant products - grains/grain products,

legumes, vegetables

• Endogenous proteins– Desquamated mucoasal cells– Digestive enzymes & glycoproteins


Digestion & Absorption

• Protein digestion– Mouth & esophagus - none– Stomach

• HCl denatures• Pepsin hydrolyzes peptide bonds



– 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



• Intestinal brush border membrane amino acid & peptide absorption– Amino acid transport

• Carriers required - passive & active transporters

– Peptide transport• PEPT1 • Co-movement of protons (H+)



• 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



– Intestinal glutamine metabolism• Primary energy source for enterocytes

– Intestinal glutamate metabolism– Intestinal aspartame metabolism– Intestinal arginine metabolism– Intestinal methionine & cysteine

metabolism



• Amino acid absorption into extraintestinal tissues– AAs enter portal vein to liver– Transport into hepatocytes– Transport into other cells -glutamyl cycle


Amino Acid Metabolism

• Metabolism of AAs includes:– Protein synthesis– Amino acid catabolism– Hepatic catabolism

• Uses of aromatic amino acids• Uses of sulfur-containing amino acids• Uses of branched-chain amino acids• Uses of other amino acids

– Plasma amino acids & pools


Synthesis of Plasma Proteins, Nitrogen-Containing 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)




• 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)




– Carnosine - may be antioxidant– Choline - methyl donor, part of

acetylcholine & lecithin & sphingomyelin




• 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


Protein Synthesis Overview

• Insulin & glucagon• Rate of protein digestion• Leucine• Fed vs. fasted state


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



• 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



• An overview of metabolism of the carbon skeleton/-keto acid– Energy generation– Glucose & ketone body production– Cholesterol production– Fatty acid production


Hepatic Catabolism & Uses of Aromatic Amino Acids

• Phenylalanine & tyrosine– Phenylalanine converted to tyrosine by

phenylalanine hydroxylase– Tyrosine

• Degradation begins with transamination to p-hydroxyphenylpyruvate

• Tyrosine used in other tissues for synthesis of L-dopa & catecholamines

• Melanin, thyroid hormones

– Disorders of phenylalanine & tyrosine metabolism


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.


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


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


Hepatic Catabolism & Uses of the Branched-Chain Amino Acids

• Isoleucine, leucine, & valine• Taken up & transaminated

primarily in muscles


Hepatic Catabolism & Uses of Other Amino Acids

• Lysine– Ketogenic - catabolism yields acetyl

CoA– Disorders of lysine metabolism

• Threonine– 3 pathways– Disorders of threonine metabolism


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


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


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



• Skeletal muscle– Isoleucine, leucine, & valine– Nitrogen-containing compounds as

indicators of muscle mass & muscle/ protein catabolism



• 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


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)


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


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


Protein Turnover: Synthesis & Catabolism of Tissue Proteins

• Cellular protein degradation systems– Lysosomal degradation– Proteasomal degradation– Calcium or calcium-activated

proteolytic degradation


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


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



– Protein efficiency ratio– Biological value– Net protein utilization– Net dietary protein calories

percentage

• Protein information on food labels– % Daily Value



• 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



• Protein deficiency/malnutrition– Kwashiorkor

• Adequate energy with insufficient protein• Edema owing to loss of blood proteins

– Marasmus• Wasting, emaciation• Chronic insufficiency of energy & protein


Perspective 6

Protein Turnover:Starvation Compared with

Stress


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 chapter 6 protein. 2009 cengage-wadsworth functional categories catalysts -...

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