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8/8/2019 Topic 3 Amino Acid and Protein-edited
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Protein Degradation in the Human DigestiveProtein Degradation in the Human DigestiveTract Tract
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Digestion of ProteinsStomach: Pepsinogen Pepsin (max. act. pH 2)
Small Intestine: Trypsinogen Trypsin
Trypsin cleaves:
Chymotrypsinogen to chymotrypsinProelastase to elastase
Procarboxypeptidase to carboxypeptidase
Aminopeptidases (from intestinal epithelia)
Enteropeptidase
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Dynamics of Protein
And Amino Acid Metabolism
Dietary Proteins Digestion to Amino Acids
Transport in Blood to Cells
Protein Synthesis Functional Proteins
Protein Degradation In
Proteasomes Following
Tagging With Ubiquitin
Amino Acids
Metabolites
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A mino acid pool A mino acid pool
No storage facility for aminoNo storage facility for amino
acidsacids
A mino acids incorporated into
A mino acids incorporated intofunctional proteinsfunctional proteins
A mino acids in blood and A mino acids in blood and
extracellular fluid represent anextracellular fluid represent an
amino acid pool amino acid pool
A mino acids move through this A mino acids move through this
poolpool
A verage 60 kg woman A verage 60 kg woman
10 kg protein10 kg protein
170 g free amino acids in pool170 g free amino acids in pool
From: Summerlin LR (1981) Chemistry for the Life Sciences.New York: Random House p 563.
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55
Lumen
Amino Acids Oligopeptides
Intestinal Absorption
Oligopeptides
Amino Acids
Peptidase
s
Blood
Transport
Protein
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A mino acid metabolism A mino acid metabolism
Metabolism of amino acids differs, but 3Metabolism of amino acids differs, but 3
common reactions:common reactions:
TransaminationTransamination
DeaminationDeamination
Formation of ureaFormation of urea
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Transamination reactionsTransamination reactions
A mino group removed from one A mino group removed from oneamino acid and transferred toamino acid and transferred toanotheranother
Catalysed by aminotransferaseCatalysed by aminotransferaseenzymesenzymes
Nearly all transaminations transferNearly all transaminations transferamino group toamino group to EE--ketoglutarateketoglutarate Forms new ketoacid and glutamateForms new ketoacid and glutamate
(amino acid)(amino acid)
BC AA transaminations in SMBC AA transaminations in SMusually result in formation of usually result in formation of alanine (via glutamate)alanine (via glutamate) Released from muscleReleased from muscle
A llows amino groups from BC AA s A llows amino groups from BC AA sto move from SM to liver forto move from SM to liver for
disposaldisposal
From: Houston, ME. (2001) Biochemistry Primer for ExerciseScience. Champaign: Human Kinetics. p151
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TransaminationsTransaminationsGlutamate E-Ketoglutarate
+ +
Pyruvate Alanine
Glutamate E-Ketoglutarate
+ +
Oxaloacetate Aspartate
Glutamate-Pyruvate
Aminotransferase
(Alanine Transferase ALT)
Glutamate-Oxaloacetate
Aminotransferase
(Aspartate Transferase AST)
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Deamination reactionsDeamination reactions
A mino group (and H) A mino group (and H)removedremoved
Forms ammonia (NHForms ammonia (NH33)) Carbon skeleton left Carbon skeleton left can becan be Oxidised in KCOxidised in KC
used forused for
gluconeogenesisgluconeogenesis converted to fatty acidconverted to fatty acid
18 amino acids18 amino acidsglucogenic/ketogenicglucogenic/ketogenic Leucine and lysineLeucine and lysine
purely ketogenicpurely ketogenic
From: Houston, ME. (2001) Biochemistry Primer for Exercise Science.Champaign: Human Kinetics. p148
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DeaminationDeamination is also an oxidative reaction that occursis also an oxidative reaction that occursunder aerobic conditions in all tissues but especiallyunder aerobic conditions in all tissues but especiallythe liver.the liver.
DuringDuring oxidativeoxidative deaminationdeamination, an amino acid is, an amino acid isconverted into the correspondingconverted into the corresponding ketoketo acid by theacid by theremoval of the amine functional group as ammoniaremoval of the amine functional group as ammonia
and the amine functional group is replaced by theand the amine functional group is replaced by theketoneketone group.group.
The ammonia eventually goes into the urea cycle.The ammonia eventually goes into the urea cycle.
OxidativeOxidative deaminationdeamination occurs primarily onoccurs primarily on glutamicglutamicacid becauseacid because glutamicglutamic acid was the end product of acid was the end product of
manymany transaminationtransamination reactions.reactions. EnzymeEnzyme -- glutamateglutamate dehydrogenasedehydrogenase
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Oxidative DeaminationOxidative Deamination
Glutamate formed by transamination reactionsGlutamate formed by transamination reactionsis deaminated tois deaminated to EE--ketoglutarateketoglutarate
Glutamate dehydrogenaseGlutamate dehydrogenase -- N A DN A D++ or N A DPor N A DP++ isiscoenzymecoenzyme
Other AA oxidasesOther AA oxidases -- (liver, kidney) low activity(liver, kidney) low activity
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Urea cycleUrea cycle
A mmonia is toxic A mmonia is toxic
Readily ionises toReadily ionises to
ammonium ion NHammonium ion NH44++
NHNH44++ converted to ureaconverted to urea
in liver (urea cycle)in liver (urea cycle)
U
rea contains 2 x NHU
rea contains 2 x NH22
One from NHOne from NH44++
One fromOne from
aspartateaspartate
Urea excreted in urineUrea excreted in urine
From: Stryer, LS (1988) Biochemistry (3rd Ed). New York: WH Freeman& Co. p500
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Transport and detoxication of ammoniaTransport and detoxication of ammonia
A mmonia has to A mmonia has tobe transported tobe transported toliverliver
Glutamine is theGlutamine is the
major transport major transport formform
Glutamine servesGlutamine servesas a source of as a source of amine groups foramine groups forbiosynthesis.biosynthesis.
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Synthesis of ureaSynthesis of urea
LiverLiver 55--step Urea Cycle (Small Krebs c., Krebsstep Urea Cycle (Small Krebs c., Krebs--
Hensleit c., Ornitihin c.)Hensleit c., Ornitihin c.)
Uses ammonia, COUses ammonia, CO22, 3 A TP and aspartate, 3 A TP and aspartate
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Interconnection of the urea cycle with thecitrate cycle
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Metabolism of amino nitrogen
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Roles of ProteinRoles of Protein
bulk compositionbulk composition of the body (structuralof the body (structuralaspects of the cell)aspects of the cell)
oxidative metabolismoxidative metabolism (used as energy(used as energysource in energysource in energy--deficient diets)deficient diets)
enzymesenzymes (globular proteins that regulate(globular proteins that regulateand influence metabolism)and influence metabolism)
plasma proteinsplasma proteins (circulating, mobile(circulating, mobileproteins such as immune bodies)proteins such as immune bodies)
hormoneshormones (regulatory role)(regulatory role)
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Special FunctionsSpecial Functions
peptidespeptides (formation of proteins)(formation of proteins)
purines/pyrimidinespurines/pyrimidines (control of protein(control of proteinsynthesis)synthesis)
histamineshistamines (active compounds, allergies)(active compounds, allergies)
conjugated proteinsconjugated proteins (assist in the excretion(assist in the excretionof other compounds)of other compounds)
pigmentspigments (e.g., melanin, derived from(e.g., melanin, derived fromamino acids)amino acids)
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Classification Based on ChemicalConstitution
Small amino acids Glycine, A lanine
Branched amino acids Valine, Leucine, Isoleucine
Hydroxy amino acids (-OH group) Serine, Threonine
Sulfur amino acids Cysteine, Methionine
Aromatic amino acids Phenylalanine, Tyrosine, Tryptophan
Acidic amino acids and their derivatives A spartate,
A sparagine, Glutamate, Glutamine
Basic amino acids Lysine, A rginine, Histidine
Imino acid - Proline
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Required in dietRequired in diet
Humans incapable of forming requisiteHumans incapable of forming requisite
carbon skeletoncarbon skeleton
Arginine*
Histidine*
Isoleucine
LeucineValine
Lysine
Methionine
Threonine
PhenylalanineTryptophan
* Essential in children, not in adults
Essential Amino Acids in Humans
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Not required in dietNot required in diet
Can be formed from aCan be formed from a--keto acids byketo acids by
transamination and subsequenttransamination and subsequent reactionsreactions
Alanine
Asparagine
Aspartate
GlutamateGlutamine
Glycine
Proline
Serine
Cysteine (from Met*)Tyrosine (from Phe*)
* Essential amino acids
Non-Essential Amino Acids in Humans
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Major Functions of Amino Acids Derived Major Functions of Amino Acids Derived
from Dietary Proteinfrom Dietary Protein
OxidationOxidationGlycogenic amino acids:Glycogenic amino acids: ----Blood glucoseBlood glucose----EnergyEnergy
KetogenicKetogenic amino acids:amino acids: --Acetyl Acetyl CoACoA--StoredStored fatfat--EnergyEnergy
Biosynthesis of nitrogenBiosynthesis of nitrogen--containing metabolitescontaining metabolites
Heme Blood cell
Choline Physiological-signaling,
neurotransmission
Glycosamine Sugar
Nucleotides DNA
Protein synthesis Protein
Biogenic amines Neurotransmitters
Carnitine Heart
Creatine phosphate « Energy »
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ProteinsProteins A mino A cid: Basic building block of protein A mino A cid: Basic building block of protein
Contain at least one amine (NHContain at least one amine (NH22) and one) and onecarboxyl group (COOH).carboxyl group (COOH).
Difference lies in their side chain.Difference lies in their side chain.
A mino A cids are joined by peptide bonds A mino A cids are joined by peptide bonds
Two AA = DipeptidetripeptidepolypeptideTwo AA = Dipeptidetripeptidepolypeptide
Polypeptides can be in several different Polypeptides can be in several different arrangements. A K A structural proteins.arrangements. A K A structural proteins.
A single cell contains thousands of A single cell contains thousands of different protein molecules.different protein molecules.
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Fig 13.3 The four levels of organization in proteins.Fig 13.3 The four levels of organization in proteins.
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All All the amino acids exceptthe amino acids except prolineprolinecontain a free amino group and a freecontain a free amino group and a free
carboxyl group.carboxyl group.
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ProteinsProteins
20 Different AAs required by20 Different AAs required bybody (Found in plants & animals)body (Found in plants & animals)
Essential : (8) Can not beEssential : (8) Can not besynthesizedsynthesized
NonNon--Essential : (12) Can beEssential : (12) Can bemanufactured by the bodymanufactured by the body
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ProteinsProteins
IngestedIngested
Plant vs A nimal: Neither is superiorPlant vs A nimal: Neither is superior
Synthesized by BodySynthesized by Body
TransaminationTransamination
Synthesis of AA s from carbon, oxygen,Synthesis of AA s from carbon, oxygen,& hydrogen fragments of carbs & lipids.& hydrogen fragments of carbs & lipids.
Often times simply transfer of amineOften times simply transfer of aminegroupgroup
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ProteinsProteins
DeaminationDeamination
Amino group is removed from AA. Amino group is removed from AA.
Remaining carbon skeleton can then beRemaining carbon skeleton can then be
converted to carbohydrate or lipid.converted to carbohydrate or lipid.Remaining amino group forms urea inRemaining amino group forms urea in
liver and is excreted by kidneys.liver and is excreted by kidneys.
Approximately 100 g of protein is Approximately 100 g of protein isbroken down and rebuilt every day.broken down and rebuilt every day.
80 g80 g pp urine , 20 gurine , 20 g pp feces & sweatfeces & sweat
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T he Stereochemistry of Amino Acids
Chiral molecules existing in two forms
http://www.imb-jena.de/~rake/Bioinformatics_WEB/gifs/amino_acids_chiral.gif
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The two stereoisomers of alanine
Ecarbon is a chiral center
Two stereoisomers are
called enantiomers.
The solid wedge-shaped bondsproject out of the plane of paper, the dashed bonds
behind it.
The horizontal bonds project out of the plane of paper, thevertical bonds behind.
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DN A mRN A protein
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Recommended IntakeRecommended Intake
Recommended intake increasesRecommended intake increasesSLIGHTLYSLIGHTLY with stress, disease,with stress, disease,
injury, prolonged heat exposure, andinjury, prolonged heat exposure, andintense strength training.intense strength training.
Increased protein needs for athletesIncreased protein needs for athletesare usually met by the increasedare usually met by the increasedprotein intake as result of increasedprotein intake as result of increased
caloric intake.caloric intake.
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Excess ProteinExcess Protein
Will not increase muscle mass orWill not increase muscle mass orprotein stores in body.protein stores in body.
ALL ALL excess protein is deaminatedexcess protein is deaminatedand used as energy or stored asand used as energy or stored as
F A T.F A T.
Very taxing on liver and kidneys!! Very taxing on liver and kidneys!!