15 Nucleotide Metabolism

DNA

What nucleic acid serves as the genetic material in cells?

RNA

What nucleic acid is responsible for protein synthesis?

Nucleotides

What type of molecules act as carriers of activated intermediates, such as UDP and CDP?

Nucleotides

What nucleotide-based compounds serve as structural components of coenzymes like Coenzyme A, FAD, NAD, and NADP?

Nucleotides

What nucleotide derivative functions as a secondary messenger, such as cGMP?

Purines

What class of nitrogenous bases includes adenine and guanine?

Adenine

Which purine base is found in both DNA and RNA and pairs with thymine or uracil?

Guanine

Which purine base is found in both DNA and RNA and pairs with cytosine?

Pyrimidines

What class of nitrogenous bases includes cytosine, uracil, and thymine?

Cytosine

Which pyrimidine base is found in both DNA and RNA and pairs with guanine?

Uracil

Which pyrimidine base is found only in RNA and pairs with adenine?

Thymine

Which pyrimidine base is found only in DNA and pairs with adenine?

Nucleoside

What molecule is composed of a nitrogenous base attached to a sugar?

Base + Sugar

What is the structure of a nucleoside?

Nucleotide

What molecule contains a nitrogenous base, a sugar, and one or more phosphate groups?

Base + Sugar + Phosphate

What is the structure of a nucleotide?

Liver

In what organ does purine nucleotide synthesis primarily occur?

Cytoplasm

In what cellular location does purine nucleotide synthesis take place?

De novo and salvage pathways

What are the two pathways for purine nucleotide synthesis?

Ribose-5-phosphate

What molecule from the pentose phosphate pathway serves as a starting substrate for purine synthesis?

Glycine, glutamine, aspartate

What amino acids are required as substrates for purine synthesis?

CO₂

What gas contributes carbon to the purine ring during synthesis?

N¹⁰-formyl-THF

What folate-derived cofactor provides one-carbon units for purine synthesis?

Step-by-step on ribose

How is the purine ring constructed during purine nucleotide synthesis?

PRPP synthesis

What is the first step in purine nucleotide synthesis involving ribose activation?

PRPP synthetase

Which enzyme converts ribose-5-phosphate to PRPP?

Ribose-5-phosphate

What substrate is converted into PRPP?

Inorganic phosphate

What activates PRPP synthetase?

Purine nucleotides

What inhibits PRPP synthetase?

PRPP + glutamine → 5-phosphoribosylamine

What is the committed step in purine nucleotide synthesis?

Glutamine-PRPP amidotransferase

Which enzyme catalyzes the committed step of purine synthesis?

Glutamine-PRPP amidotransferase

What regulates the committed step of purine synthesis?

AMP, GMP, and IMP

What molecules inhibit glutamine-PRPP amidotransferase?

PRPP

What molecule activates glutamine-PRPP amidotransferase?

IMP (inosine monophosphate)

What purine nucleotide is first formed in de novo purine synthesis?

Glycine, aspartate, glutamine, CO₂, THF derivatives

What amino acids and molecules are required for IMP synthesis?

IMP

What molecule serves as the precursor for both AMP and GMP?

Aspartate

What amino acid is required for the conversion of IMP to AMP?

Adenylosuccinate synthetase and adenylosuccinate lyase

Which enzymes catalyze the formation of AMP from IMP?

IMP

From which nucleotide precursor is AMP synthesized?

GTP

What energy source is required for IMP → AMP?

Glutamine

What amino acid is required for the conversion of IMP to GMP?

ATP

What energy source is needed for IMP → GMP?

IMP dehydrogenase and GMP synthetase

Which enzymes convert IMP to GMP?

IMP

From which nucleotide precursor is GMP synthesized?

AMP, GMP, and IMP

Which molecules provide feedback inhibition in purine synthesis?

Feedback inhibition

What type of regulation occurs when AMP, GMP, and IMP inhibit purine synthesis?

Cross-regulation

What ensures balanced purine nucleotide synthesis between AMP and GMP?

GTP

Which energy molecule is required to synthesize AMP, ensuring balance with GMP synthesis?

ATP

Which energy molecule is required to synthesize GMP, ensuring balance with AMP synthesis?

Adenine phosphoribosyl transferase (APRT)

Which enzyme salvages adenine to form AMP?

Hypoxanthine-guanine phosphoribosyl transferase (HGPRT)

Which enzyme salvages hypoxanthine and guanine to form IMP and GMP?

HGPRT

What enzyme is deficient in Lesch-Nyhan syndrome?

Hyperuricemia

What metabolic abnormality results from HGPRT deficiency?

Decreased

What happens to purine reutilization in Lesch-Nyhan syndrome?

Increased

What happens to purine synthesis in Lesch-Nyhan syndrome due to loss of salvage pathway activity?

Ribonucleotide reductase

What enzyme converts ribonucleotides to deoxyribonucleotides?

Purine and pyrimidine nucleoside diphosphates

What type of molecules are reduced by ribonucleotide reductase?

Deoxyribonucleotides

What is the product of ribonucleotide reductase activity?

Sulfhydryl groups on ribonucleotide reductase

What provides the hydrogen atoms needed to reduce the 2′-hydroxyl group during deoxyribonucleotide synthesis?

dATP

What molecule acts as an allosteric inhibitor of ribonucleotide reductase?

Inhibits ribonucleotide reductase allosterically

What is the regulatory effect of dATP on deoxyribonucleotide synthesis?

Intestines and kidneys

Where does purine degradation primarily occur?

Uric acid

What is the final product of purine degradation in humans?

Through urine

How is uric acid eliminated from the body?

Purine nucleotides → nucleosides → free bases → uric acid

What is the general sequence of purine breakdown?

5′-nucleotidase

What enzyme converts AMP to adenosine in purine degradation?

Adenosine

What is AMP converted to during purine degradation?

5′-nucleotidase

What enzyme converts GMP to guanosine in purine degradation?

Guanosine

What is GMP converted to during purine degradation?

Nucleosides

In the purine degradation pathway, nucleotides are first converted into what class of molecules?

Adenosine deaminase

What enzyme converts adenosine to inosine in purine degradation?

Removes an amino group (deamination)

What reaction does adenosine deaminase perform?

Inosine

What is adenosine converted into during purine degradation?

Hypoxanthine

What is inosine converted into after deamination?

Guanine

What is guanosine converted into during purine degradation?

Purine nucleoside phosphorylase

Which enzyme converts inosine to hypoxanthine and guanosine to guanine?

Ribose sugar

What does purine nucleoside phosphorylase cleave during purine degradation?

Xanthine oxidase

What enzyme converts hypoxanthine to xanthine?

Xanthine

What is hypoxanthine converted into during purine degradation?

Guanine deaminase

What enzyme converts guanine to xanthine?

Deamination of guanine to form xanthine

What reaction does guanine deaminase perform?

Xanthine

What is guanine converted into during purine degradation?

Xanthine oxidase

What enzyme converts xanthine to uric acid?

Uric acid

What is xanthine converted into in the final step of purine degradation?

Poorly soluble

Is uric acid highly soluble or poorly soluble in plasma?

Excreted in the kidneys

How is uric acid eliminated from the body?

Xanthine oxidase

What is the main enzyme responsible for uric acid production?

No

Does xanthine oxidase have strong feedback inhibition?

Allopurinol and febuxostat

What drugs inhibit xanthine oxidase?

Colchicine

What drug used in acute gout inhibits microtubule formation?

Decreases neutrophil movement

How does colchicine reduce gout inflammation?

Prednisone

What corticosteroid can be used to treat gout inflammation?

Allopurinol

Which drug is a structural analog of hypoxanthine used in gout treatment?

Inhibits uric acid synthesis by inhibiting xanthine oxidase

How does allopurinol reduce uric acid levels?

Allopurinol

Which drug competitively inhibits xanthine oxidase?

Febuxostat

Which gout medication is a non-purine xanthine oxidase inhibitor?

Cytoplasm and mitochondria

Where does pyrimidine synthesis occur in the cell?

Before (ring built first, then attached to ribose)

In pyrimidine synthesis, is the ring built before or after attaching to ribose?

Pyrimidine ring is built first, then attached to ribose

How does the construction of the pyrimidine ring differ from purine synthesis?