20 y 21. Purines Y Pirimidines

Nitrogenated Bases

Purines and pyrimidines

Purine Ring

heterocyclic aromatic organic

compound, consisting of a pyrimidine ring

fused to an imidazole ring. (9 atoms, 4 of them are N)

Pyrimidine Ring

A heterocyclic aromatic

organic compound containing two nitrogen

atoms at positions 1 and 3 of the six-member ring.

Purine Bases

Adenine and Guanine

Pyrimidine Bases

Cytosine, thymine, uracil

Adenine

Guanine

Cytosine

Thymine

Uracil

What nitrogenous base is only used in RNA?

Uracil

What nitrogenous base is only used in DNA?

Thymine

Nucleosides

Nitrogenous base attatched to a sugar via a glycosidic bond.

Pentose sugars

Ribose and Deoxyribose

Ribose sugar

Has two OH groups (2 and 3). Used for RNA.

Deoxyribose Sugar

Has an OH an H group in C2. Used for DNA.

Nucleotides

Building blocks of nucleic acids, composed of a sugar, a phosphate group(s), and one purine/pirimidine

Condiciones en el metabolismo de nucleotidos suelen ser a nivel?

Mitocondrial

Links the nucleotides in DNA/RNA?

Phosphodiester bonds

Formation of phosphodiester bonds

C 3' with a C 5'

Nucleotides son precursores de que?

Nucleic Acids

Nucelotides are carriers of what type of energy?

Chemical (ATP, GTP, etc)

Nucleotides used as energy

If the body is in need of immidiate energy, the body may use nucleotides.

Are Nucleotides components of coenzymes?

True (FADH2, FMN, NADH…)

What type of effectors are nucleotides?

Allosteric effectors (positive and negative)

Are nucleotides physiological mediators?

Yes, they work as secondary messengers (cAMP and cGMP)

de novo pathways

Synthesize of purine and pyrimidine nucleotides from low molecular weight precursors. Uses a lot of energy.

Los de novo pathways son casi idénticos en todos los organismos?

Si

Como se le llama una mutación en de novo pathways?

muerte

Salvage Pathways

Synthesis of nucleotides from nucleosides or bases that become available through the diet or from degradation of nucleic acids.

Como se le llama a las mutaciones en Salvage pathways?

Mutaciones

Cual es el paso regulatorio en Purine biosynthesis: de novo pathways?

PRPP —> PRA

Cual es la enzima que da el rate limiting step en Purine biosynthesis: de novo pathways?

Glutamine-PRPP amidotransferase

Glycine

Precursor in the purine de novo pathway that forms more than one atom at the same time. Two carbons and one nitrogen.

First intermediate to have a complete purine ring and the first intermediate for the formation of ATP?

IMP (inosine monophosphate)

What inhibits Ribose 5-P —> PRPP

ADP

What inhibits PRPP—> 5-Phosphoribosylamine?

AMP, IMP and GMP. Increases Km.

Que es el 1?

CO2

Que es el 2?

Glycine

Que es el 3?

Formate

Que es el 4?

Amide N of glutamine

Que es el 5?

Aspartate

Where all reactions of the purine de novo pathways occur?

Cytosol

En Purine Salvage que hacen las Two Distinct Phosphoribosyl Transferases?

Conserves energy

Cuales son las Two Distinct Phosphoribosyl Transferases de Purine Salvage ?

APRTase

HGPRTase

Lesch-Nyhan syndrome

Disorder caused by HGPRTase deficiency, inherited as an X-linked trait. Seen mainly in males.

Lesch-Nyhan syndrome symptoms?

Automutilación

Increased blood and uric acid levels

Delayed Motor Development

Lesch-Nyhan syndrome treatment?

Allopurinol

Adenosine deaminase deficiency

Immunodeficiency disease (SCID), deficient in T and B cells.

Cual es la causa de Adenosine deaminase deficiency?

Codificación en el cromosoma 20

Como se puede tratar Adenosine deaminase deficiency?

Terapia Genetica

Purine Nucleoside phosphorylase (PNP)

Rare autosomal recessive genetic desease. DNA synthesis can't occur and cells can't replicate.

PNP is caused by

dGTP build up which inhibit ribonucleic reductase.

PNP symptoms

growth failure, cellular immunodeficiency, recurrent infections, cerebral vasculitis…

PNP treatment?

Stem cell transplantation

Gout

Accumulation of uric acid in articulations and tissues

Cual es la condición mas común relacionada con acido úrico?

Gout

Gout Treatment?

Alloprupinol

Colchicine = previene ataques

Indomethacin = Alivia Dolor e hinchazón

Probenecid = Baja niveles de acido urico

Rate limiting or regulating step of pyrimidine de novo pathway?

Carbomyl phosphate synthetase II (CPS-II)

Que es el 1?

Glutamine Amide

Que es el 2?

Aspartate

First intermediate of the pyrimidine de novo pathway. Inhibits the rate limiting step.

UTP

Important in the Salvage pathway

PRPRTase

Synthesis of Red Blood Cells in the pyrimidine salvage pathway

Uses orotate, uracil and thymine, but NOT cytosine.

Type I orotic aciduria

A disease caused by the lack the UMP synthase

Type II orotic aciduria

Due to a deficiency only of orotidine-5'-decarboxylase.

Orotic aciduria symptoms

Elevated urinary orotate, megaloblastic anemica, recurrent infections, developmental disabilities.

Uridine, Uridylic and cytidylic acid

Treatment for Orotic aciduria

Que es lo mas importante para la regulacion de reducatasa?

Glutation

dTMP

Suicide inhibitor

Antitumor agents

thymidylate synthase and dihydrofolate reductase.

Fluorouracil

a thymidylate synthase inhibitor. Used in chemotherapy.

Methotrexate and aminopterin

Inhibit the metabolism of folic acid. They are enzyme inhibidors.