Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
89 Cards in this Set
- Front
- Back
|
. |
. |
|
|
. |
. |
|
|
. |
. |
|
|
Proteinogen aa |
21 with 20 in aa pool. SeC U |
|
|
Positive aa |
R.Arg H.His K.lys |
|
|
Neg aa |
D.asp E.glu |
|
|
Polar uncharged aa |
S.Ser T.Thr N.Asn Q.Gln |
|
|
Special aa |
C.cys U.sec G.Gly P.Pro |
|
|
Hydrophilic aa |
A.Ala V.Val I.Ile L.Leu M.Met F.Phe Y.Tyr W.Trp |
|
|
Types of proteogenic aa based on being essential and what is deg based on and the products of pathway determine Types of proteogenic aa based on being essential and what is deg based on and the products of pathway determine Types of proteogenic aa based on being essential and what is deg based on and the products of pathway determine |
Essential(indespensible) Conditionally essential Nonessential(despensible) Based on end product Product pathway determine glycogenic and ketogenic nature of aa |
|
|
Comm features of proteinogic vs nonproteinogenic aa |
L config except achirl glycine Alpha amino except imino proline All genetically coded D amino Intermediates or products of biosynth pathways eg ornithine gaba ldopa beta ala Some are antimetabolites Nature plant products often part of defense mechanism Some activated by tRNA and built into proteins so proteomimetrics |
|
|
Proteomimetric aa. |
Mistakenly util in prot synth after tRNA Canavanine arg analog: Autoimmune disease, made by plants like beans meta-Tyr analog: interferes root dev by replacing phe
|
|
|
Sources of proteins and aa and amounts. Fate of aa |
|
|
|
Essential vs conditionally essential list |
Aromatic aa Phe Trp vs Tyr Branched aa leu val ile thr Sulfur aa met vs cys Basic aa lys vs his and arg Other conditionally essential gly gln pro
Based on n balance measurements of rat and human |
|
|
Conditional essential aa list Noncond list |
Arg synth but rate is insufficient for growth Cys from met but if met low then need supply Tyr synth from Phe but if phe bla His is essential for infants. Only intestinal bacterial supply.
Nonessential or dispensivlr aa ala asp asn glu ser
Essentially may occur at cellular tissue level eg for Asn Gln
Nutritional value of prot dep on aa comp and microbiota composition |
|
|
Role of aa |
|
|
|
Aa composition |
|
|
|
Protein vs carbs and lipid metabolism |
Aa give alphhKG suc CoA fumarata and OAA pyrivate Degredation of ketogenic require mit and o2 and they can't be converted to glucose Tag to glycerol FA to acoa to tca Glycogen to glucose to pyruvate to lactate and OAA and accoa |
|
|
Carbs lipds and aa central intermediate central pathway storage and essentiality |
|
|
|
Protein digestion |
Aa di and tri peptides absorbed. Exception IgG uptake lafter birth Avg daily intake 70 to 100g Abs 170 200g the extra from sloughed off cells and from digedtivr enxymes Predom Na Cotranspoeter in the form aa di and tri anf these are hydrolzed intracellular enterocytes |
|
|
Stomach duodenum intestin and GI tract micriobiota modulated |
|
|
|
Endo aa sourcr via intracell prot brkdwn |
Lysosomal: 5 ph. Hydrolyses(prot nuc and polysaccharidases) prot to aa
Ubiquit dep prot: neutral, atp dep degradation in proteasomes
Significance: dig if prot for rapid destruction and of misfoldedd denat and abn
|
|
|
AA transport |
Solute carrier (slc) Aa trans are group specific Carrier mediated en dep Na dep and indep Na cotransp(energy ti pump ion) Monomeric and dimeric |
|
|
Aa transporter diseases |
|
|
|
Gamma glutamyl cycle |
Active at intensive transport sites (renal and intestinal brush) mainly cys gln It is de novo peptide synth
Aa goes to gamma glutamyl transpeptidase (memb bound) + gluthatione to give gamma glutamyl aa (to gamma coo) and cys-gly
and Former goes thru gammaglutamyl cyclotransferase to give Original AA and 5-Oxoproline(pyroglutamate) that goes thru oxoprolinase using atp to givr glutamate 5-Oxoproline(pyroglutamate) that goes thru oxoprolinase using atp to givr glutamate
Cys-gly breaks into cys and gly with former reacting with glutamate made via gamma glutamylcysteine synthase and using ATP go give gamma glutamylcysteine
That reacts with glycine made earlier via gluthathio synthase to give gluthathione Note that Glutathione forms a gamma glutamyl enz complex and that glutathione inhibits gamma glutamylcysteine synthase |
|
|
Gamma glutamyl cycle prob: gluthathione synthase deficiency |
Gluthathione synthase deficience: oxoprolin-, aminoaciduria, hemolytic anemia and mental retardation. Acidosis due to oxorpolinemia ...gammaglutamylcysteine, 5oxoproline and gamma glutamylcystein increase but gluthathione decreases so no inhibition of gamma glutamylcystein syntethase
Gamma glutamylcysteine is a product of gamma glutamyl cyclotransferase thats ahy oxoprol increases
|
|
|
Gamma glutamyl cysrein synthase def |
Aminoaciduria hemolyic anemja but no acidosis as no oxoprolinemia and mental retardation Everything is reduced including transported aa and maybe oxoprol,gly and cys. |
|
|
Oxoprolinase deficiency and oxoprolinemia-oxoprolinuria |
Rare Anemia mental ret Oxoprolinemia and oxoprolinuria metabolic acidosis So 5oxoproline is not used to make glutamate and increases in conc. Inherited: gluthathione synthase def and oxoprolinase def Aquired: chronic acetaminophen as its metabolite conjugates and depletes gluthathione |
|
|
GSH |
mM conc in cells. Stabile resistsnt to proteases. Composition: gamma glutamyl-cysteinyl-glycine Function: 1. intracell reductant as GSH/GSSG >>1 Gluthatione peroxidase reductase system is major h2o2 met for many tissue Gluthathiotranshydrogenases: thiol-disulfide exchage using GSH for prot synth def and enz act and deact 2.precursor of S-subsituted GSH deriv Gluthathione S-transferases Exogenenous comp: mercapturate formation (n acetylated, s subsituted cys deriv) Endo: leukotriene(eicosanoid inflamm med from oxid of arachidonic) synth 3.coenzyme as many enz use GSH Eg. Glyoxyalase, cis ttans isomer isomerization by maleylscetoacetate isomerase 4.aa trans DIAGNOSTIC: gamma GT increases in liver could mean obstructive jaundice and its levels is a marker for alcohol induced liver disease and cirrhosis |
|
|
Common reactions in aa metabolism like how we use different aa parts |
|
|
|
Fate of nitrogen |
Role of transA: usual way of aa deg, funneling of N into glutamate, quantitative importance, NOT ELIMINATE N FROM AA Classification of transA: several. Dep on cytoplasmic or mitochondria. Dep on reactants, pos of amino group(alpha or beta) Diagnostic: asp amino transf and serum glutamate OAA transaminase in liver (mainlg cytosolic), heart other organs. Role of transA: usual way of aa deg, funneling of N into glutamate, quantitative importance, NOT ELIMINATE N FROM AAClassification of transA: several. Dep on cytoplasmic or mitochondria. Dep on reactants, pos of amino group(alpha or beta)Diagnostic: asp amino transf and serum glutamate OAA transaminase in liver (mainlg cytosolic), heart other organs.Alanine amino transferase and serum glutamate pyruvate transaminase in liver cytosolic and mitchondria ,other organsDeamination is removal of N from aa pool . Oxid using red cofactors (NAD(P) FAD FMN). Aa reduces cofactor to give imino acid and then water is used to give ammonia and ketoacidnonox using intramolecular intramolecular Alanine amino transferase and serum glutamate pyruvate transaminase in liver cytosolic and mitchondria ,other organs Deamination is removal of N from aa pool . Oxid using red cofactors (NAD(P) FAD FMN). Aa reduces cofactor to give imino acid and then water is used to give ammonia and ketoacid nonox using intramolecular intramolecular |
|
|
GDH |
Glud1 is high capacity and irreversible? While other is reversible. Glud1 is main gate removing N and opens in low energy so deg muscle proteins. ADP HIGH Glud1 is high capacity and irreversible? While other is reversible. Glud1 is main gate removing N and opens in low energy so deg muscle proteins. ADP HIGHIf energy high (GTP not atp cuz more specific) protein is reservedIf energy okay but too many protein leucine overrides gtp affect and fat stored If energy high (GTP not atp cuz more specific) protein is reserved If energy okay but too many protein leucine overrides gtp affect and fat stored |
|
|
Transdeamination general scheme |
|
|
|
Gdh1 mutations |
Loss of Func mut: neurodeg disorders Gain of func mut: hyperinsulinism/hyperammonemia (hi/ha) synd: 1.mutant enz show reduced sensitivity towards GTP inhb but can be act by ADp so increased aKG and NH3 2.increased aKG stimulates TCA and oxphos so insulin and hypoglycemia 3.GDH overact depletes Glu, less N-Ac-Glu and prevent urea cycle initiation |
|
|
Structure of GDH |
Its glud1 Homohexameric GTP closes it and prevent the product from leaving Movement is via a pivot helix and this js what diseases inhibit |
|
|
Glud1 act and effect of (BCAAs) leu |
Leu into panc and musc via lat1 Panc: leu stims glud1 and glu to aKG(goes to tca) using NADP+ to give NADP and NH4+. Atp from tca inhibits potassium channel so no K+ in so memb depols Brings Ca thru Ca channel and insulin gran to exo insulin to insR at musc Irs stims akt stims mTORC1 (leu stims too as kinase as leu is a goos sensor for aa pool) so we need to make proteins and inhibits 4EBP1 |
|
|
Oxidases and nonoxid deamination |
D-amino: a: FAD. High act on glycine and damino substrates L: fmn low act and role in lys deg Nonoxid deamin: Beta elimination via dehydr(ser thr) or desulfhydr(cys) with PLP Ser to imino (loss of water) to pyruvate (gain if water but loss of ammonium) Ammonia lyase: his to urokanate(loss of ammonium). Common in lower org and we introduce a double bond (happens on skin) as urokanate is uv abs and protects uv and uv light mediated immune supression. BUT IF DEFICIENT I THINK WE DO AS DEAMINASE Lys and thr no transaminases These are peroxosomal reactions so no energy Dehyd or desulf gives us an oxid comp that has same fate as imino |
|
|
His ammonia lyase def |
Histidinemia: False positive for PKU as forms inosidol pyruvate? Phenyl pyrvuate green. Frequent. Speech and mental problems. Verified by skim biopsy. |
|
|
PLP |
Derivative of pyridoxine (b6) Contains subsituted pyridine Plp provides aldehyde group for schif base and bottom serine Ring has nitrogen e deficient so its an e sink Bonds broken by taking the electron and protein forces serine bond perpendicular to N so out of screen. |
|
|
Mech of transamination |
Plp cov attached to enzy via a schiff (imine) In transamination nucleophilic amino of aa substrate attacks enz-PLP schiff Tautomerization thru resonancr carbanion int aKG-PMP hydrolyzed to produce PMP and aketoacid Reg of PLP occurs in reverse way using aketoacid as substrate
Aldimine gives quinonoid int gives ketimine gives pyridoxamine phos phosphate ( ox red hydr) and aketoacid |
|
|
How does PLP cat diff enzymes |
Stereoelectric(bending perp to pi orbital of orbital sink). Protein part determines of specificty of an enzyme
|
|
|
Form and elim ammonia |
Norm blood level:30-60 microM Higher than 100 hyperammonemi coma
Toxicity due ti BBB perm Thru glutamate dehydrogenase causes aKG depletion Increases Glu thag is exitotoxic as its a neurotrans
Ammonia in astrocyte mit causes ROS snd damage
Sources: glutamate dehyd : reversible enzyme. In periportal hepatocytes it releazes ammonia for synth cabamoyl phosphate to urea
Specific deamination: b elimination( srtine dehyx and desulfhydrase) histidine ammonia lyaze
Glutaminase and asparginase reactions using water (glu to gln) Intestinal bacteria Purine and pyrmidine deg (adenylate deaminase, adenosine deaminase, cytidine and guanine deaminase) adenosine using water gives inosine and ammonoium Purine nucleotide cycle Amine oxidase reaction Eliminatw neurotransmittwrs by removing ammonia - mau reactions so neurons hav ammonia to be removed Pyrimidine ring nitrogen is a source |
|
|
Purine nucleotide cycle and amine oxidase reaction |
|
|
|
Aa metabolism in tissues |
Int: utilises glu gln and asn asp to givr ala and citrulline and ammonia MUSC: releases ala (glucose-ala) gln(binds ammonia released from purine nucleotide cycle) and transamination of bcaa BRAIN: glu, asp gly neurotrans, amine oxidase reactions and NH4 elimination in the form of Gln LIVER: center of aa metabolism. High km enz( aa tRNA synthase low km). Periportal cellz( glutaminases, glutamatedehyrogenase, ure) Perivenous cycle( glutamine synthaze) KIDNEY: glutaminase activity NH4+ and urea secretion RAPID DIV CELLS: Gln utilization, aKG prod (anaplerosis). Gln is also for nucleotide synthesis |
|
|
N trans between organs |
|
|
|
Deamination |
N removed from aa pool In oxidative using reducing cofactors or nonoxidative using intramolecular oxidation Nad(p) FAD OR FMN Aa to imino by reducing cofactor to keto by hydroxylation deamination |
|
|
Carbamoyl phosphate synthetase 1 and regulation |
Not technically urea cycle enzyme Catalyzes cond and act of bicarbinaye and ammonium
Bicaronate is activated using ATP to give carbonyl phosphate
Then organic phosphate ammonium exchange gives carbamate
Carbamate activation using atp to give carbamoyl phosphate CP Regulation: in short term reg by arg and leu but arg is essential
|
|
|
Carbonyl phosphate other name |
Carbonic acid phosphoric acid anhydride |
|
|
CPS 1 VS CPS 2 |
Prpp is the active ribose needed for nucleotide synth
Nucleotide metabolism is absolutely dependent on aa metabolism Atp also activates cps2 |
|
|
Urea cycle |
Citrulline made is nonproteogenic
2.Argininosuccinate made via ASS and ATP(to amp)
3.Arg made by losing fumarate. Ultimately aspartate transaminated to citrulline. ASL
4. Ornithine via arginase by losing urea
5. Ornithine enters mit via ORNT1 and gains CP to form Cyt
|
|
|
Problems with urea cycle |
Remember lysine looks like ornithine Any enz deficient and the precursor become -urenemia and hyper-emia Ass deficiency causes citrullinemia Asl deficiency causes argininosuccinaturlinemia If oct1 kaput then no acceptor of CP i believe lysine is used instead forming homocystein(urine) but DEAD END. - HHH syndrome Highest hyperammonemia i believe is at first level |
|
|
HHH |
Hyperonithinemia Hyperammonemia Homocitrullinemia Rare autosomal Ornithine translocase deficiency Treatment: discontinuation of protein intake Intravenous infusions of glucose with supplement of arg and Ammonia removal drugs |
|
|
Purine and pyrimidine degredation (and other ammonia releasing stuff) |
Adenylate, adenosine, cytidine and guanine deaminases Pyrimidine ring is an energy source Intestinal bacteria also produce ammonia |
|
|
What shuttle is the urea cycle coupled with |
|
|
|
Enzyme deficiencies of cp synth and urea cycle (not wiki) |
Complete enz deficiency not compatible Partial deficiencies > hyperammonemia N-A-Glu synthetase: hyper aa emia, mental retardation. Therapy: low p, alpha ketoacid benzoate and phenyl acetate ARG adminstration(s?) OTC deficiency: X LINKED orotic aciduria MOST COMMON ASS deficiency: type I citrullinemia, citrullinuria ASL: argininosuccinate acc Arginase: very rare and MR Citrin: blocked Asp from mit to cyto TYPE II CITRULLINEMIA, citrullinuria ORNT1 HHH Nongenetic enz deficiencies: cirrhosis and acquired hepatic coma. |
|
|
Alternative to urea cycle |
Benzoate + CoA using ATP but we release AMP and PPi Then addition of glycine for CoA to make Hippurate(benzoglycine) Phenylacetate + glutamine after many cycles via CoA and using ATP to release AMP and PPi gives phenylacetylglutamine |
|
|
Intercellular glutamine cycle properties |
Urea synth plays a role in acid base balance Shared function of liver and kidney 1 ammonium exc means proton elim too
Localization: 1.periportal hepatocytes: glutaminase, GDH and CPS I, urea cycle enzymes
2.perivenous hepatocytes: glutamine synthetase
3.kidney: glutaminase and GDH
Note single liver lobe is 1 and 2 |
|
|
Intercellular glutamine cycle |
|
|
|
Decarboxylation (oxidative) |
aketodehydrogenase enz complexes family 1.PDH 2.aKGDH 3.Branched Chain aKeto acidic Dehyd Complex BCKDC
Parts: 1.dehydrogenase 2.dihydrolipoyl transacylase 3.dihydrolipoyl reductase(SAME IN COMPLEXES)
PDCK inactivates PDC using atp and we reactivate via hydration and Pi removal
BCKDCK does the same for BCKDC
Aa to aKa aKa to ACoA reducing NAD (release h) Cofactors: CoA SH, FAD TPP lipoamide |
|
|
BCKDC deficiency |
Maple syrup urine disease (MSUD) AR Severe acidosis and MR Treatment: some benefit from thiamine admin Mennonite mutation(founder effect) and impedes tetramerization Tyr of alpha of E1 (a2b2) hetratetramer mut to asn Tetramerization of E1 affected by mutation E1 of BCKDC has TPP cofactor |
|
|
Rare hereditary autism |
Low blood bcaa Could be BCKDCKinase deficiency Low blood in Val Leu Ile means increaaed Phe Tyr Trp by LAT1 |
|
|
Role of oxidative decarb in aa metabolism |
Leu, Val Ile via aKG/Glu transamination give bcaa then via BCKDC we get AcoA Met and thr via transsulf+transmeth and dehydratasd respectively give aKB to propionylCoA via BCKDC Trp, Lys to aKadipate to glutaryl CoA |
|
|
Nonoxidative Decarb |
PLP or piruvyl group cofactors With latter the enz : proteolytic cleavage of one subunit of homodimeric precursor yields Ser as N-Terminal aa. It undergoes a dehyd prod a pyruvyl N terminal Blocking group Role in aa met: Elimination of omega carboxyl of glutarylCoA (lys trp deg) Formation of neurotrans: precursor functions |
|
|
Carboxylation |
Cofactor biotin ALWAYS Evol 2 poss: 1.CO2 util: less capacity? But more reactive. K dep carboxylases and PEPCK 2.Bicarbonate higher cap but less reac. CPS1 biotin dep carboxylases Biotin dep carboxylation: At least 3 subunits or multifunctional prots Deg propionyl CoA from aa The familiae biotin mechanism of bicarbonate + ATP to give E-biotin-COO that transfers to substrate EX(PyruvateCarboxylase Priopionyl CoA Carbox AcCoA carboxylase ) carboxylation in deg of leu Ile val met the to propionyl coA to d MethylmalonylcoA |
|
|
C1 units |
Methyl n5 Methylene n5 to 10 Methenyl n5 to 10 Formyl CHO n5 or 10 Formimino CH=NH2 n5
|
|
|
Methyl donors also intra vs extracell |
Methyl FH4 Betaine Methyl B12 SAM
Folic acid is a methyl carrier Comp: 2amino4hydroxy6methylpteridine pamino benzoate glutamate(n)
The subsituted pteridine has N=C in the ring that are important Intracell N>1 Extra is 1
|
|
|
FH4 and its transport |
Tetrahydrofolate F-Glu(7)(DHR?) to FH4-Glu(7) via Dihydrofolatereduxtase (DHFR) Loses 6 via GCP2 at apical brush border Then into circulation its methylated (primary biologically active) And via RFC(reduced folate carrier?) and FR(folate receptor?) into cell Loses methyl to b12 Then gets 6 more glu |
|
|
C1 transfer main pathway and nucleotide |
His to formimino-FH4 to(-NH4) methenyl FH4
Trp to Formate to Formyl FH4(N) by using ATP and FH4 and losing ADP Pi Via MTHFD1
Methyenyl FH4 to Formyl FH4 by using H2O via MTHFD1 to purine nucleotide synthesis Or methenyl FH4 to methylene FH4(N) via NADH H oxidation and MTHFD1 to FH2 via dUMP to dTMP conversion to FH2 (IRREVERSIBLE) via TS
1.FH2 to FH4 (B) via DHFR and reduction NADPH H (inhibited dihydrofolate reductase can be blocked by antimetabolites like aminopterine ametopterine(methotrexate) ) 2.FH4(B) formation directly via PLP SHMT using gly to ser B. Reversible reaction uses a diff enzyme so GS abd releases NH4+ and bicarbonate
3.using MTHFR and NADPH H and FAD we make methyl FH4 (IRREVERSIBLE) sam inhibits.
MethylFH4(C) (IRREVERSIBLY) to FH4 using C1 sources like ser gly his and trp
|
|
|
Transmethyl of C1 |
Methylene FH4(N) to FH4(B) using gly to ser +PLP Or To methyl FH4 (C)via MTHFR NADPH H FAD
Methyl FH4 + B12 forms FH4 and methyl B12 via a MS(+MSR) -transmeth
Methyl b12 trans meth to homocys to form met and b12 using i think MS MSR
Met can also be formed via homocys to met IRREVERSIBLE using betain to dimethylglycine
Met converts to SAM using ATP to PPi Pi via MAT
SAM converts to SAH using methyl carriee or to dcSAM (polyamines) and it inhibits methyl FH4 formation. SAH to homocys using SAHH |
|
|
Transulf of C1 |
Homocys to cistationine: PLP and CBS using ser to H2O Cysrathione ro cys Using CGL and PLP and H20 for aKB used for propionyl CoA formation |
|
|
Transmeth and sulf genetic defects |
MTHFR mutation also dissociates the tetramer and loss of fad as it switches to monomeric form. Mild homocyst and inc atherscelrosis chance |
|
|
Betaine and b12 srructure |
A special methyl donor Phosphatidyl serine + 3SAM > phosphatidyl choline + CO2 + 3SAH
To choline Oxid to betainaldehyde Oxid to betaine Homocys + betaine > met + dimethyl glycine Oxid to 2 Formate and glycine Properties: While SAM is general methyl donor, specialised methyl donor using one step are methyl THF and betaine in a b12 independent way End product is met, 2 formate and glycine. |
|
|
SAM |
Its a methyl and propylamine donor (easily loses adenosine and via meth or carbox gives propylamine to make choliamine and without it we can't do cell division. Choliamine synth is target for therapeutic intervention THIS IS A NON PLP as very ancient. So uses piruvyl cofactor to decarboxylates SAM and thats used as propylamine donor i polyamine synth Otherwise methyl carrier takes methyl to form SAH |
|
|
reactions of DHFR |
Folate to DHF to THF both each use NADPH H
Folic acid is the vitamin (from.foliage) |
|
|
Sulfonamides and folate analogues |
Bacteria synth TH4 and if we inhibit we block bacterial nucleotide synth and cell div Sulfanamides were used as antibacterial drugs as they have pteridine? Methotrexatw used in cancer therapy as TH4 antimetabolite and its a DHFR inhibitor |
|
|
Serine hydroxymethyltransferase |
Ser to gly using THF to mTHF and PLP Functional dimer Bonds perpendicular to pi bond of this and asp aminotransferase |
|
|
MTHFR structure |
Homotetrameric with ab barrel Fad Amp of fad Mut cauaes dissociation and loss of fad |
|
|
Fate metabolism and transmethylation deficiencies |
DHFR Causes magaloblastic anemia. Therapy: formyl FH4 add(most stable c1 unit) Methylene FH4 reductase: hyperhomocysemia uria and dev delau and cns probs Formimotransferase we excrete formiminoglutamate B12 due to usually malabsorption mTHF trap > folic acid js jn trap anemia perniciosa Nucleotide synth impaired as low folate Methylmalonyl CoA mutase affected so branched chain fa synthesised neuroprobla Folic malabsorption megoblastic anemia and common in alcoholics Same problems but differ by L methymalonyl CoA acidonemia if b12 as methyl malonic acid? And meth mal coA looks like m CoA so competes for fa synth and membranes are bad so csnt exclude water and myelin sheat problems occur. |
|
|
B12 def |
|
|
|
Monooxy and dioxy |
Bh4 is reducing cofactor as it provides 2 H for water. Bh4 is made so not vitamin. Former: one O makes hydroxyl while the other makes water with H of cofactor So its technically hydroxylation in aa met. Phe deg. Neurotrans synth from tyr abd trp. Aromaric aa hydroxylase enzyme family. Thjs famkly comon is BH4 and cat domain has high ho.ology so subs diff Reg domail little homology. |
|
|
Aromatic amino acid hydroxylases |
|
|
|
Phenyl alanine hydroxylase properties |
Homotetramer Reg: Allosteric act by Phe cooperativity Inh by BH4 Act by phosphorylation PKA |
|
|
Phenyl alanine hydroxylase |
In liver and kidney This is classical PKU if deficient if BH4 then nonclassical. Bh4 is for all aromatic aa so affects tyr and trp hydroxylation too
BH2 and qBH2 differ in how double bonds are arranged and they are isoforms diff substrates for enz At the bottom thats tyr. |
|
|
Pterins |
Redox cofactors With the pterin ring Resembles isoalloxazine ring of flavin coenz And so too partic in redox Biopterin and folate both have em and act in tetrhydro form. |
|
|
Enz deficiencies of Phe to Tyr |
PAH: classical PKU AR MR and livht skin colour. Therapy is low PA BH4 reductase: tyr and trp hydroxylation deficient too. Cns seriously affected. Therapy: 5hydroxytryptophan and DOPA admin Maternal PKU Enz of BH2 Syth: cofactor synth from GTP failure and may also be affected due to deficiency of enz cat process |
|
|
PAH structure |
Non heme iron containing Active in tetra Fe2+ in centre not FeS cluster Mut can be in active site BH4 bindinf site or other regions |
|
|
Dioxy |
Both O enter substrate Opens aromatic rings Degs Phe and Tyr Tyr Tyr |
|
|
Alkaptonuria |
Ochronosis with black urine when air exposed. Homogentistic acid was the cause. NaOH also blackens Large vit C helps cure. |
|
|
Dioxy in trp deg |
This formyl group goes to 1C and by removing alanine we eventually end up with the bottom left If u get rid of the O2 on the bottom right and sat the doublr bonds and u end up with aa which is converted to brta oxid? |
