Transcript lect6
BIOC/DENT/PHCY 230 LECTURE 6
Lecture 6: Nitrogen Metabolism III Amino acids as a source of nitrogen for biosynthesis of specialised compounds and nucleotides
Unde rstand why ami no ac ids are precursors for specialis ed compound s and nuc leotides.
Be famil iar wit h the notable features of
de novo
bio synthes is of purines and pyrimidines.
Be aware of the bene fits of nuc leotide salvage pathway s.
Note the ve ry different end produc ts of pur ine and pyr imi dine degr adation.
Know that the product from pur ine degradation is uric acid and why it can cause medical problems .
Expl ain so me of the bene fit s to medicine of unde rstand ing nitrogen metaboli sm.
Nucleotides
found in DNA and RNA used for energy (ATP and GTP) building blocks for coenzymes (NADH)
Building blocks for nucleotides
Two classes of bases
Two types of ribose
Synthesis of nucleotides
nucleotide bases can be recycled or synthesised de novo purine bases are synthesised on ribose pyrimidine bases are synthesised independent of ribose
Synthesis of PRPP
PRPP contributes ribose phosphate to nucleotides formation catalysed by PRPP synthetase AMP PRPP synthetase is allosterically inhibited by AMP, ADP and GDP.
De novo purine synthesis
Glutamine donates an amide to initiate purine synthesis A whole glycine is added to the nitrogen
The coenzyme tetrahydrofolate donates a formyl group Glutamine donates a second amide
Imidazole ring is closed in an energy dependent reaction
Aspartate is added in an energy dependent reaction This is analogous to the urea cycle
Ring closure Tetrahydrofolate donates a second formyl group
Origins of purine base
IMP can be converted to GMP and AMP
De novo pyrimidine synthesis
The pyrimidine base is synthesised before being attached to ribose
ring closure and oxidation
Ribose is now added via PRPP
UMP can be used to synthesise CTP
Origins of pyrimidine base
Comparison of purine and pyrimidine biosynthesis
Base synthesis Amino acids Other molecules ATP purines on ribose gln(2), asp, gly formate(2) HCO 3 5
(AMP,GMP)
pyrimidines free asp CMP gln carbamoyl phosphate 2
(UMP)
3
Ribonucleotides are used as precursors for deoxyribonucleotides
ATP GTP CTP UTP dATP dGTP dCTP dUTP Ribonucleotide reductase
Thymidine nucleotides are derived from dUMP
Tetrahydrofolate donates a methyl group
Degradation of pyrimidine nucleotides CTP UTP
b
-alanine, NH 3 , CO 2
Degradation of purine nucleotides
Free ammonia is also produced in muscle
during severe muscle activity ATP 2ADP ADP + P i ATP + AMP AMP
AMP deaminase
IMP + NH 4 +
Degradation of purine nucleotides
GOUT
uric acid is quite insoluble excess uric acid can crystallise in joints gout can be treated with allopurinol allopurinol is a competitive inhibitor of xanthine oxidase
The take home message
nucleotides have a number of functions they can be synthesised de novo if required some steps are analogous with the urea cycle amino acids provide many of the components synthesis is regulated by the concentrations of various nucleotides synthesis is energetically expensive the degradation of excess purines can cause gout