Thesynthesisofnonessentialamino The synthesis of non essential amino acids

AtifHKhirelsied,BSc,MSc,PhD.

DepartmentofBiochemistry FacultyofMedicine Faculty of Medicine InternationalUniversityofAfrica,Khartoum,Sudan

Essential Essential
Isoleucine Leucine Valine Lysine Methionine Phenylalanine Threonine Tryptophan Arginine Histidine

Non essential Nonessential

Alanine Aspartate Asparagine Cysteine Glutamate Glutamine Glycine Gl i Proline Serine S i Tyrosine

Biological importance of amino acids

Biosynthesisofbodyproteins. Biosynthesisofnonproteinsnitrogenouscompounds. y p g p Catabolismtoketo acids(energygeneration). Catabolism to keto acids (energy generation)

Sources of amino acid pool

Dietaryproteins. Breakdownoftissueproteins. Breakdown of tissue proteins. Biosynthesisofnonessentialaminoacids. Biosynthesis of nonessential amino acids

Non-essential amino acids

Haveshortsyntheticpathways. Formedbyamination ofmetabolicintermediates. y Someareformedfromessentialaminoacids. Some are formed from essential amino acids

Nutritional value of proteins

BiosynthesisofNonessentialAminoAcids: Biosynthesis of Nonessential Amino Acids:

NonessentialaminoacidsareformedbyTHREE general mechanisms: 1. 1 Transamination 2. Assimilationoffreeammonia 3. Modificationofexistingaminoacids.

Transamination

Transamination
Requirespyridoxal phosphate(PLP). PLPboundtoalysineresidueintheactivesiteofthe enzyme. ItformsaSchiffbaseintermediateduringthereaction. g

Glutamate synthesis
Glutamte isformedbyreductiveamination ofketo glutarate catalyzedbyglutamatedehydrogenase enzyme.

Glutamate synthesis
Glutamte canalsobesynthesizedbytransamination reaction.

COO | C=O | CH2 | CH2 | COO COO

Aminoketo acidacid

COO | CHNH3+ | CH2 | CH2 | COO COO

Glutamate

ketoglutarate

Glutamine synthesis
Glutamineisformedbythe Glutamine is formed by the amidation ofglutamate.

Alanine synthesis
Formationofalanine b t F ti f l i bytransamination ofpyruvate,catalyzed i ti f t t l d byalanine transaminase.

Aspartate synthesis

Aspartateissynthesizedbytransaminationofoxaloacetate

Asparagine synthesis
Aspartate is formed by amidation of aspartate catalyzed by isformedbyamidation ofaspartate catalyzedby asparagine synthetase.
COO | CHNH3+ | CH2 | COO
Aspartate

GlutamineGlutamate

ATPAMP+PPi

COO | CHNH3+ | CH2 | CONH2

Asparagine

Serine synthesis
Serineissynthesizedbythetransaminationand y y dephosphorylation of3phosphogylcerate.

Glycine synthesis
Synthesisinmammaliantissuescanoccurinseveralways Synthesis in mammalian tissues can occur in several ways Itcanbeformedfromseveralprecursorsincluding; It can be formed from several precursors including;
1. 2. 2 3. 4. 4 Serine Choline glyoxylate Carbondioxideandammonia C b di id d i

Glycine synthesis
Serinehydroxymethyltransferase cansynthesize glycine from serine fromserine

Serinehydroxymethyltransferase

Glycine synthesis
Theenzymes The enzymes 1. 2. 2 3. Choline dehydrogenase, Betaine dehydrogenase dehydrogenase, Betainehomocysteine N methyltransferase, methyltransferase 4. 5. 5 Sarcosine demethylase Sarcosine oxidase,. S i id
3 1 2

Glycine synthesis
Inthelivercytosol glycine transaminase canuseglyoxylate andglutamatetoformglycine. g gy The liver mitochondrial enzyme glycine synthetase use Thelivermitochondrialenzymeglycine use N5,N10CH2H4folate toformglycine fromCO2 andNH4

Tyrosine synthesis
DihydrobiopterineReductase Dihydrobiopterine Reductase

Phenylalaninehydroxylase

Tyrosinesynthesis
Isformedfromphenylalanineinareactioncatalyzedby phenylalaninehydroxylase. Thereactionusestetrahydrobiopterin asprotondonor y p p Phenylalaninehydroxylase isamixedfunctionoxygenase y y y yg presentinliver. Deficiencyoftheenzymeorthecofactorcauses phenylketonuria.

Phenylketonuria

Cysteine synthesis

Cysteinecontainsatomsdonatedby
bothmethionine andserine. b th thi i d i

Cysteine synthesis

Cysteinecontainsatoms
donatedbyboth d t d b b th methionine andserine.

Proline isformedfromglutamate

ProlineDehydrogenase

ProlineDehydrogenase

Hydroxyproline andhydroxlysine
Principally found in collagen Principallyfoundincollagen Is formed by hydroxylation of peptide bound proline and Isformedbyhydroxylationofpeptideboundproline and lysinebyprolyl andlysyl hydroxylase. Theenzymesarepeptideshydroxylases requiremolecular oxygenascorbate,ferrousionandketoglutarate oxygen ascorbate ferrous ion and ketoglutarate

Selenocysteine
Selenocyteine arisescotranslational modificationof serine. Ispresentintheactivesiteofseveralenzymesincluding; Thioredoxin reductase Glutathioneperoxidase p Deiodinase

Selenocysteine
ThetRNAsec isfirstchargedwithserinebyserine amionacyltransferase Subsequentlytheserineoxygenisreplacedwith selenium Seleniumisintroducedasselenophosphate formedby selenophosphate synthase.

Valine,leucine,andisoleucine a e, euc e, a d so euc e

Canbesynthesizedbytransamination oftheirrespective keto acids Thusvaline,leucine andisoleucine aredietaryessential aminoacids,butcanbereplacedbyketoisovalarate, ketomethylvalarate andketoisocaproate respectively

Histidine andarginine
Histidine andarginine aresemiessential. They are adequately synthesized in adult people but are Theyareadequatelysynthesizedinadultpeoplebutare nutritionallyessentialforchildren Histidine isrequiredforthenormalgrowthoflongbones

Asummaryofpathwaysinvolved inthesynthesisofnonessential aminoacids. amino acids