Nucleotides metabolismEnmin Li

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, mmol dAMP, dGMP, dCMP, dTMP, mol* Nucleosides: Adenosine, Guanosine, Cytidine, Uridine Deoxyadenosine, Deoxyguanosine, Deoxycytidine, Thymidine * Bases: Adenine, Guanine, Cytosine, Thymine, UracilIngestionSmall intestine epithelial cellsNotes

-alanineIn small intestine cells, liver cells and kidney cellsUMPCMPUracil Cytosine Thymine dTMPNucleotidaseNucleosidase NucleotidaseNucleosidase NucleotidaseNucleosidase -aminoisobutyric acidDihydrouracil Dihydrothymine -uraminopropionReductase -uraminoisobutyric acidReductase Dihydrothyminase Dihydrouracilase -uraminopropionase-uraminoisobutyric acidase

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

AMP deaminase and diabetes

Jenkins RL, McDaniel HG, Atkins L.Changes in AMP deaminase activities in the hearts of diabetic rats. Biochim Biophys Acta. 1991 Apr 29;1077(3):379-84Department of Biology, Samford University, Birmingham, AL 35229. AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).

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

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

? 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