ΘΕΜΑ 12345 ΕΡΓΑΣΙA ΔΕΥΤΕΡΗ

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ΓΡΑΠΤΗ ΕΡΓΑΣΙΑ ΒΙΟΛΟΓΙΑΣ ΕΑΠ

Text of ΘΕΜΑ 12345 ΕΡΓΑΣΙA ΔΕΥΤΕΡΗ

1 , (2--D- D- DNA RNA ) . . . DNA RNA , ATP, GTP, CTP UTP. , de novo . de novo , , . To . , , (UMP) (CMP). , , C . . , , . -, NH3 CO2. (PP) , .

, HPLC Mass Spectrometry. . PP , Lesch-Nyhan , . . ( ), ( ). , RNA, . [1]

1.1 .

1.2. 1.1. , DNA, -. [2]

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(A) (G) (C) (U) (T)).

(AMP) (GMP) (CMP) (UMP) (TMP)

1.1 RNA (

1.2 .

- . [2]

, . , (UMP), RNA. [2]

(CMP) , - (UDP) - (UTP), ATP. [2] UMP + ATP UDP + ADP UDP + ATP UTP + ADP - (CTP) , . [2] UTP + (3) + ATP CTP + ADP + Pi +

4

1.3 de novo

- -, , - . [2]

, . . [2]

6

1.4 .

C , 1.5. [2] , . [2]

1.5 C .

. . . ( ), , . , 3 CO2. [2]

1.6 .

8

1.7 AMP . . pH . , .

-, 3 CO2. , . - , -, 3 CO2. , -. [2]

1.8 .

(PP) reviews . - , . PP , . , . . (high-performance liquid chromatography, HPLC), (mass spectrometry), , . . , , . [4] , . , .

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PP . . PP , . o . . [5] , , , , , ,

, , , , gout . , (.. 5-fluorouracil azathioprine ). , . [5]

(gouty arthritis) , . ( + = ),

. [3]

, . 1/3 , 2/3 . 3,5-7,2 mg/dL , 2,6-6,0 mg/dL 2,0-5,5 mg/dL . 7 mg/dL (, hyperuricaemia), , , ( ), , . , (). , . . 40 , . o , . : (peak), , . , , . . , 30% . [3]

( Gout = , ipperlein), , ,

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. Gout , . . , . H ( Gouty rthritis), , , , (, , , ). ( ), , ,

, , ( , ). () , . [3]

(). , () . :

1. , , , , .. 2. . 3. , , . 4. , (.. Lesch-Nyhan). 5. ( ). 6. : .

7. . 8. pH . 9. (, , ). , , ( ). , , . [3]

( Lesh-Nyhan) GPRT (----) . H : () . () Lesch-Nyhan ( ). () (Glycogen Storage Disease). () . , (). , . [3]

:

(Purine turnover): , , . , , . . X .

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(Cytotoxic drugs). , , , . : (

, ). . [3] , . , . [3]

Lesch-Nyhan

NCBI, Lesch-Nyhan (LNS) : , , , , , . (van der Zee et al., 1968). [6] (HPRT) Lesch-Nyhan Kelley-Seegmiller. To LNS . , KelleySeegmiller . , KelleySeegmiller, LNS. , Kelley-Seegmiller (gout). (1,5 8%),

(Jinnah and Friedman, 2001). [7] 1979, Bakay HPRT, , , . ( ). HPRT , . [8] Page , HPRT, . 7,5% . . , , . [9] 2008, Hladnik , HPRT . Lesch-Nyhan, , , . , , , . , gout IQ. , . [10] 1977, Vogel Lesch-Nyhan, . [11] 1965 (Hoefnagel et al.) HPRT. [12]

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1. McMurry J. , , . 29, . 1395-1398, 2004. 2. . ,, .; . 6, . 134-158, 2000. 3. . 4. Jurecka A. Inborn errors of purine and pyrimidine metabolism, J Inherit Metab Dis. 2009 Apr; 32(2):247-63, Epub 2009 Mar 15. 5. Simmons HA, Duley JA, FairbanksLD, McBride MB. When to investigate for pyurine and pyrimidine disorders. Introduction and review of clinical and laboratory indications., J Inherit Metab Dis. 1997 Jun; 20(2):214-26. 6. Van der Zee, S. P. M.; Schretlen, E. D. A. M.; Monnens, L. A. H. : Megaloblastic anaemia in the Lesch-Nyhan syndrome. (Letter) Lancet 291: 1427 only, 1968. Note: Originally Volume I. 7. Jinnah, H. A.; Friedmann, T. : Lesch-Nyhan disease and its variants.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic & Molecular Bases of Inherited Disease. Vol. II. 8th ed. New York: McGrawHill 2001. P. 2537. 8. Bakay, B.; Nissinen, E.; Sweetman, L.; Francke, U.; Nyhan, W. L. : Utilization of purines by an HPRT variant in an intelligent, nonmutilative patient with features of the Lesch-Nyhan syndrome. Pediat. Res. 13: 13651370, 1979. PubMed ID : 523196 9. Page, T.; Nyhan, W. L.; Morena de Vega, V. : Syndrome of mild mental retardation, spastic gait, and skeletal malformations in a family with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase. Pediatrics 79: 713-717, 1987. PubMed ID : 3575027 10. Hladnik, U.; Nyhan, W. L.; Bertelli, M. : Variable expression of HPRT deficiency in 5 members of a family with the same mutation. Arch. Neurol. 65: 1240-1243, 2008. PubMed ID : 18779430 11. Vogel, F. : A probable sex difference in some mutation rates. (Editorial) Am. J. Hum. Genet. 29: 312-319, 1977. PubMed ID : 868880 12. Hoefnagel, D.; Andrew, E. D.; Mireault, N. G.; Berndt, W. O. : Hereditary choreoathetosis, self-mutilation and hyperuricemia in young males. New Eng. J. Med. 273: 130-135, 1965. PubMed ID : 14303658

2 , RNA . RNA , , , . RNA . RNA -P, , , HDV glmS. . , , . RNA , . , . ,

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. H . . RNA . , , . , . . HDV. glmS . RNA o RNA , .. . Cech RNA . ( 413 ) Tetrahymena thermophila. , Zaug . Thermophila in trans, (.. RNA). Foster Symons RNA (virusoid RNAs) RNA . Uhlenbeck , (hammerhead ribozyme), . RNA

,

-

RNA,

. Haseloff Gerlach , in trans. , in vivo. in vivo 60% . , . [1] in vivo , in vitro . . [1] MichaelisMenton. , Kcat/Km. 108 -1 min-1. cat/Km , Km Kcat , , [1]. , , . , (single turnover reaction), . (Kalavrizioti et al., 2006). [6] in vitro, : gel ,

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. . , . : , . , . RNA. , . [1] . , . [1] RA . (self-splicing RNA) RNA P (RNase P) tRNAs, RNA . 1980, RNA (small nucleolytic ribozymes or RNA-based enzymes). : (hammerhead) , (hairpin ribozyme), (hepatitis delta virus, HDV) Neurospora crassa Varkud satellite (VS). RNA RNA (ligation reaction). [2] , , 3,5- RNA. , RNA RNase P tRNAs ( 1a). , o (transesterification),

( 1b) ( 1c,d). 3,5- , RNA 2,3- 5 ( 1b). , o , pH . RNA, . in vitro leadzyme, RNase A riboswitch glmS, RNA . [2] , ( 1c,d). 3-OH 5 , , 3 . 3- . ( 1c). , 2,3 , 2,5- . , 2 ( 1d). RNA , . tRNA Eukarya Archaea , , 2,3- . [2]

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2.1 RNA. (a) tRNA RNase P 5- tRNA 3- 5 . (b-d) (b) , (c) , (d) . (b), 2- 3,5- , 2,3- 5-.

(c), 3- (G) 5- 5 , 5 . , 5 3,5 3 , . (d), , . (e) .

RNA . RNA , RNA ( 1e). RNA . RNA rRNA. [2] , RNA , riboswitch . 1 RNAs. RNA ; , RNA, . [2]

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2.1 riboswitches.

RNA , . ,

. , , . , , . [2] ,