Metabolisme Nukleotida
-
Upload
qd-vella-qnozesdante -
Category
Documents
-
view
135 -
download
7
description
Transcript of Metabolisme Nukleotida
![Page 1: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/1.jpg)
Metabolisme Nukleotida
SAA
![Page 2: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/2.jpg)
Outline
• Pengertian Nukleotida
• Struktur
• Fungsi
• Kepentingan Biomedis
• Metabolisme Purin dan Pirimidin
• Asam Nukleat
![Page 3: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/3.jpg)
Apa itu nukleotida
• Basa heterosiklik aromatik
• Purin
• Pirimidin
• Unit monomer asam nukleat
• Komponen koenzim
• Nukleosida ?
![Page 4: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/4.jpg)
struktur
![Page 5: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/5.jpg)
Tata Nama
• Adenin (A)
• Guanin (G)
• Timin (T)
• Sitosin (C)
• Angka 3
• Angka 5
• Adanya ikatan fosfodiester
![Page 6: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/6.jpg)
Fungsi
• Pemindahan fosfat
• Fungsi regulasi
• Fungsi second messenger
• Prekursor monomer materi genetik
![Page 7: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/7.jpg)
Kepentingan Biomedis
• Analog purin dan pirimidin digunakan dlm terapi penyakit kanker
• Pengobatan penyakit gout
• Supresi sistem imun
• Hasil metabolisme sebagai komponen batu sal kencing
![Page 8: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/8.jpg)
Metabolisme Nukleotida
• Pencernaan
• Katabolisme
• Biosintesis
• Kelainan
![Page 9: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/9.jpg)
Pencernaan
• Adanya enzim-enzim RNA ase, DAN ase dan polinukleotidase (endonuklease dan fosfodiesterase))
• Enzim fosfatase
• Tidak ada incorporasi nukleotida lewat pencernaan
• Asam nukleat diet ------- purin + pirimidin
![Page 10: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/10.jpg)
Katabolisme
• Purin ----------- asam urat
• Pirimidin --------- CO2, amoniak, beta aminoisobutirat,alanin
• Tidak membutuhkan nukleotida dari diet
![Page 11: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/11.jpg)
Biosintesis
• Bersifat de novo ; inosin monopospat
• Fosforibosilasi purin
• Fosforilasi nukleosida purin
![Page 12: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/12.jpg)
![Page 13: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/13.jpg)
Synthesis of the first fully formed purine nucleotide, inosine monophosphate, IMP begins with 5-phospho-a-ribosyl-1-pyrophosphate, PRPP. Through a series of reactions utilizing ATP, tetrahydrofolate (THF) derivatives, glutamine, glycine and aspartate this pathway yields IMP. The two indicated enzymes (A and B) are those catalyzing the rate limiting step and the reaction necessary for the purine nucleotide cycle, respectively. The structure of the nucleobase of IMP (hypoxanthine) is shown.Abbreviations: PRP: 5-phosphoribosylamine; GAR: 5-phosphoribosylglycinamide; FGAR: 5-phosphoribosyl-N-formylglycinamide FGAM: 5-phosphoribosyl-N-formylglycinamidine AIR: 5-phosphoribosylaminoimidazole CAIR: 1-(5-phosphoribosyl)-5-amino-4-carboxyimidazole SAICAR: 1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole AICAR: 1-(5-phosphoribosyl)-5-amino-4-imidazolecarboxamide FAICAR: 1-(5-phosphoribosyl)-5-formamido-4-imidazolecarboxamide
![Page 14: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/14.jpg)
![Page 15: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/15.jpg)
![Page 16: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/16.jpg)
![Page 17: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/17.jpg)
![Page 18: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/18.jpg)
![Page 19: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/19.jpg)
![Page 20: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/20.jpg)
![Page 21: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/21.jpg)
![Page 22: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/22.jpg)
![Page 23: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/23.jpg)
![Page 24: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/24.jpg)
![Page 25: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/25.jpg)
![Page 26: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/26.jpg)
![Page 27: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/27.jpg)
Katabolisme Purin
![Page 28: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/28.jpg)
![Page 29: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/29.jpg)
Sintesis IMP
• Dari alfa D ribosa 5 pospat
• Melalui 11 reaksi
• Membuat 2 cabang (AMP dan GMP)
• Urutan reaksinya sbb
![Page 30: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/30.jpg)
Pemindahan Fosfat
• Pospat dari ATP dipindah ke AMP dan GMP
• Enzim nukleosidase monofasfat kinase
• nukleosidase difosfat kinase
![Page 31: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/31.jpg)
Reaksi Penyelamatan
• Fosforibosilasi purin bebas oleh PRPP
• Fosoforilasi ribonukleosida secara langsung
![Page 32: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/32.jpg)
Biosintesis Nukleotida Purin di Hati
• Adanya ukuran depot PRPP
• AMP dan GMP mengatur enzim PRPP
• AMP dan GMP mengatur pembentukannya dari IMP melalui feed back
• Reduksi NDP membentuk dNDP
![Page 33: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/33.jpg)
Biosintesis Pirimidin
• Pembentukan karbamoil fosfat dari glutamin ATP dan CO2
• 12 langkah lihat di gambar
![Page 34: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/34.jpg)
![Page 35: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/35.jpg)
![Page 36: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/36.jpg)
![Page 37: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/37.jpg)
Regulasi Biosintesis Pirimidin
![Page 38: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/38.jpg)
![Page 39: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/39.jpg)
![Page 40: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/40.jpg)
Regulasi Biosintesis Pirimidin
• Terjadi pada ekspresi gen dan aktifitas enzim
• Pengaturan secara terkoordinasi
![Page 41: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/41.jpg)
Kelainan Met Purin
• Gout/Hiperurisemia
• Sindrom lesch Nyhan
• Penyakit Von Gierke
• Hipourisemia
• Defisiensi Adenosin deaminase dan nukleosida purin fosforilsase
![Page 42: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/42.jpg)
Kelainan Met Pirimidin
• Ekskresi Beta Aminoisobutirat meningkat pada leukimia
• Gen resesif
• Tinggi pada orang jepang dan cina
• Ekskresi pseudouridin tetap tanpa perubahan
• Asiduria Orotat
• Defisiensi ornitin karboksilasi
![Page 43: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/43.jpg)
Disorders of Purine Metabolism
Disorder Defect Nature of Defect Comments
Gout PRPP synthetaseincreased enzyme
activity due to elevated Vmax
hyperuricemia
Gout PRPP synthetaseenzyme is resistant to feed-back inhibition
hyperuricemia
Gout PRPP synthetase
enzyme has increased affinity for ribose-5-phosphate (lowered
Km)
hyperuricemia
Gout PRPP amidotransferaseloss of feed-back
inhibition of enzymehyperuricemia
Gout HGPRTa partially defective enzyme
hyperuricemia
Lesch-Nyhan syndrome HGPRT lack of enzyme see above
SCID ADAb lack of enzyme see above
Immunodeficiency PNPc lack of enzyme see above
Renal lithiasis APRTd lack of enzyme 2,8-dihydroxyadenine renal lithiasis
Xanthinuria Xanthine oxidase lack of enzymehypouricemia and
xanthine renal lithiasis
von Gierke's disease Glucose-6-phosphatase enzyme deficiency see aboveaHypoxanthine-guanine phosphoribosyltransferase; badenosine deaminase; cpurine nucleotide phosphorylase; dadenosine phosphoribosyltransferase
![Page 44: Metabolisme Nukleotida](https://reader033.fdocument.pub/reader033/viewer/2022050818/55cf9d53550346d033ad234c/html5/thumbnails/44.jpg)
Disorders of Pyrimidine Metabolism
Disorder Defective Enzyme Comments
Orotic aciduria, Type I
orotate phosphoribosyl transferase and OMP decarboxylase
see above
Orotic aciduria, Type II
OMP decarboxylase see above
Orotic aciduria (mild, no
hematologic component)
the urea cycle enzyme, ornithine transcarbamoylase, is deficient
increased mitochondrial carbamoyl phosphate exits and augments pyrimidine biosynthesis; hepatic encephalopathy
b-aminoisobutyric
aciduria
Transaminase, affects urea cycle function during deamination of a-
amino acids to of -keto acidsbenign, frequent in Orientals
Drug induced orotic aciduria
OMP decarboxylase
Allopurinol and 6-azauridine treatments cause orotic acidurias without a hematologic component; their catabolic by-products inhibit OMP decarboxylase