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Nucleotides metabolism. Enmin Li. 论述题 -1 请从一位未来医生的角度,围绕高尿酸血症引发痛风及其生化作用机制,论述人类饮食平衡的重要性。. 论述题 -2 结合临床应用,举例论述各类抗核苷酸代谢物的作用原理。. Goutiness. Digestion, Ingestion and Degradation of Nuclear acids and Nucleotides and Nucleosides and Bases in Food. Bases/Nucleosides/Nucleotides. Base. - PowerPoint PPT Presentation
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Nucleotides metabolismEnmin Li
-1
-2
Goutiness
Digestion, Ingestion and Degradation ofNuclear acids and Nucleotides and Nucleosides and Bases in Food
Bases/Nucleosides/Nucleotides BaseNucleosideNucleotideAdenineDeoxyadenosineDeoxyadenosine 5-triphosphate(dATP)apostrophe
Nucleoproteins, RNA/DNA, Nucleotides, Nucleosides and Bases in FoodRNA/DNA, Nucleotides, Nucleosides and BasesIn stomach Nucleotides, Nucleosides and Bases In small intestineGastric acid and pepsinEndonucleases: RNase and DNase* Nucleotides: AMP, GMP, UMP, CMP, TMP, mmol dAMP, dGMP, dCMP, dTMP, mol* Nucleosides: Adenosine, Guanosine, Cytidine, Uridine, Deoxyadenosine, Deoxyguanosine, Deoxycytidine, Thymidine * Bases: Adenine, Guanine, Cytosine, Thymine, UracilIngestionSmall intestine epithelial cellsNotes
Guanine Hypoxanthine Adenine Xanthine Uric acid 4NH3 + 2CO2Allantoic acid Allantoin Glyoxylic acid Urea 12345Notes: Excreted by1 Primates, Birds, Reptiles, Insects. 2 Other mammals.3 Teleost fish. 4 Cartilaginous fish and amphibia5 Marine invertebratesThe fate of uric acid in the various animals
The uric acid and the goutUric acid Over 0.48 mmol/L, In the plasmaGout, Urate crystallization in joints, soft tissue, cartilage and kidneyOut of bodyIn urineDiabetese nephrosis
Nucleotides Biosynthesis1-3Purine Pyrimidine Adenine Guanine Cytosine Uracil Thymine de novo pathway salvage pathway
Salvage nucleotide biosynthesis pathwayPhosphoribosyl thansferase Nucleosides kinaseBasesAdenine, Guanine, Hypoxanthine, Thymine, UracilAdenosine, Guanosine, Cytidine, Uridine, or Deoxy, Thymidine ATPPRPP(APRT, HGPRT)
Hypoxanthine-guanine phosphoribosyl transferase on X chromosomeLoss of HGPRT leads to elevated PRPP levels and stimulation of de novo purine synthesis. One ultimate consequence is increased production of uric acid.
De novo nucleotide biosynthesis pathway
The main bases on nucleotides or nucleosidesin the tautomeric forms predominant at pH7.
The metabolic origin of the six atoms in the pyrimidine ring Aspartate Carbamyl-P
CTPUTPUDPATPPRPP+_The regulatory circuits that control pyrimidine synthesis in E.coli and animals.
The metabolic origin of the nine atoms in the purine ring Glutamine (amide-N)Glycine Aspartate N10-formyl-THFN10-formyl-THFFirst, synthesis Inosine-5'-Monophosphate, IMP
5-,PRA OH0ATPAMPGln:PRPP amidotransferase
5-
5--4-(N-)-7Carboxyaminoimidazole ribonucleotide (CAIR)
5--4-8
5--4-9
10
Second, Making AMP and GMP
ADPGDPATPGTPGDPAMPGTPGDPADPGTPATPADPGMPATPADP, ATP, GDP and GTP biosynthesis
Ribonucleotide reductaseAllosteric regulation 225462
The free radical mechanism of ribonucleotide reduction unit unitsubstrate
1 mnqnllvtkr dgsterinld kihrvldwaa eglhnvsisq velrshiqfy dgiktsdihe 61 tiikaaadli srdapdyqyl aarlaifhlr kkaygqfepp alydhvvkmv emgkydnhll 121 edyteeefkq mdtfidhdrd mtfsyaavkq legkylvqnr vtgeiyesaq flyilvaacl 181 fsnypretrl qyvkrfydav stfkislptp imsgvrtptr qfsscvliec gdsldsinat 241 ssaivkyvsq ragiginagr iralgspirg geafhtgcip fykhfqtavk scsqggvrgg 301 aatlfypmwh levesllvlk nnrgvegnrv rhmdygvqin klmytrllkg editlfspsd 361 vpglydaffa dqeeferlyt kyekddsirk qrvkavelfs lmmqerastg riyiqnvdhc 421 nthspfdpai apvrqsnlcl eialptkpln dvndengeia lctlsafnlg ainnldelee 481 lailavrald alldyqdypi paakrgamgr rtlgigvinf ayylakhgkr ysdgsannlt 541 hktfeaiqyy llkasnelak eqgacpwfne ttyakgilpi dtykkdldti aneplhydwe 601 alresikthg lrnstlsalm psetssqisn atngiepprg yvsikaskdg ilrqvvpdye 661 hlhdayellw empgndgylq lvgimqkfid qsisantnyd psrfpsgkvp mqqllkdllt 721 aykfgvktly yqntrdgaed aqddlvpsiq ddgcesgack i http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&id=2507304Ribonucleoside diphosphate reductase 1 subunit alpha 225439462
Regulation of dNTP Synthesis
Allosteric regulation of nucleotide reductaseSubstrates Products Activators Inhibitors ADPdATPdGTPdATPGDPdGTPdTTPdATPCDPdCTPATPdATP, dGTP, dTTPUDPdTTPATPdATP, dGTP
PRPPGln6MPAzaserine PRAGARFGARFGAMMTXAzaserine AICARFAICARIMPAMPGMPPPiPRPPAIGPRPPPPiThe mechanism of the Chemotherapeutic Agents-1MTX6MP6MP6MP6MPAzaserine MTXAzaserine6-MP6
UMPUDPUTPdUDPdUMPdTMPCTPCDPdCDPMTX5FU (5FdUMP/5FUTP)CytarabineAzaserineThe mechanism of the Chemotherapeutic Agents-2
? A. B. C. D. E.
2. 5-A. DNAB. C. D. E.
3. A. B. C. D. E.
4. A. B. 6-C. 1-D. 1,6-E. 5-
5. A. B. C. D. E.
6. , ?A. B. C. D. E.
7. -CMPAMPTMPUMPIMP
, ?GTP-
9. PRPP, A. R-5-PPRPPB. C. PRPPD. IMPAMPE. IMPGMP
10. A. 5-B. FH4C. D. E.
11. The supreme tissue of de nove synthesis of purine nucleotide in vivo isA. thymus glandB. villous coat of small intestineC. liverD. spleenE. marrow
12. The main end product of purine nucleotide katabolic metabolism in human body isA. ureaB. creatineC. CreatinineD. uric acidE. -alanine
13. The methyl of thymine come fromN10-CHO FH4N5,N10=CH-FH4N5,N10-CH2-FH4N5-CH3FH4N5-CH=NHFH4
14. 6-mercapto-purine nucleotide doesnt suppressA. IMPAMPB. IMPGMPC. PRPP amide transferaseD. Purine phosphoribosyltransferaseE. Pyrimidine phosphoribosyltransferase
15. A B CO2C D E
16. PRPPA B C D NMPNDPNTP
17. A B C D
18. A B C
19. The compound which can produce feedback suppression of purine nucleotide synthesis is A IMPB AMPC GMPD uric acid
20. Which compound produce uric acid as its decomposed metabolism end product ?A AMPB UMPC IMPD TMP