Biochemistry Metabolism - LIMES-Institut

Gerhild van Echten-Deckert

Tel. 73 2703E-mail: [email protected]

NucleotideMetabolism

Biochemistry

Metabolism

07.11.2017 – 27.11.2017

Physiological Function of Nucleotides

-Building blocks of nucleic acids

-High energy donors-ATP, GTP-UDP-Glc, CDP-Choline...

-Cofactors-NAD+, FAD, CoA, (SAM)

-Metabolic control- as allosteric modulators-as second messengers (cAMP, cGMP)

Purine and pyrimidine bases of nucleic acids

Hydrogen-bonding patterns in the base pairs defined by Watson and Crick

Voet, Voet: Biochemistry

The biosynthetic origins of purine ring atoms

Strategy of purine biosynthesis

Berg, Tymoczko, Stryer: Biochemistry

De novo purine biosynthesis


Purine biosynthesis (I)


Purine biosynthesis (II)


Purine biosynthesis (III)


Purine biosynthesis (IV)


Conversion of IMP to AMP and GMP


NMP kinases are base-specific but do not discriminate between NMP and dNMP.NDP kinases are non specific regarding both, the bases and the sugar.

Control of purine-biosynthesis

Voet&Voet: Biochemistry

Ribose phosphate pyrophosphokinaseActivated by: PPi, 2,3 bisphosphoglycerateInhibited by: ADP, GDP

Amidophosphoribosyl-transferase

AMP and GMP compete with IMP

Reciprocal control of AMP and GMP formation by GTP and ATP, respectively.

Levels of adenine and guanine nucleotidesindependently but synergistically controlthe rate of IMP formation


The biosynthetic origins of pyrimidine ring atoms


Strategy of pyrimidine biosynthesis

De novo pyrimidine biosynthesis


Explanation for the accumulationof uracil and orotic acid in caseof deficient OTC (urea cycle)

CTP is generated from UTP


Nelson, Cox: Lehninger Biochemistry

Control of pyrimidne biosynthesis

Remember: ADP and GDP arefeed-back inhibitors of ribosephosphate pyrophosphokinase

Biochemistry Metabolism - LIMES-Institut

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