Nucleic acid metabolism

What happens during DNA/RNA turnover?

DNA/RNA are degraded into free bases, which are either salvaged or degraded to waste products (e.g. uric acid)

What are the two pathways of nucleotide metabolism?

De novo synthesis and salvage (reusage) pathway

Why is the salvage pathway important?

It is energy efficient, faster, and especially important in rapidly dividing cells like lymphocytes

What is the final product of purine degradation in humans?

Uric acid

Which enzyme converts hypoxanthine → xanthine → uric acid?

Which enzyme converts hypoxanthine → xanthine → uric acid?

What reactive by-products are produced by xanthine oxidase?

Reactive oxygen species (ROS) such as superoxide (O₂⁻) and H₂O₂

What enzyme is deficient in ADA-SCID?

Adenosine deaminase (ADA)

Adenosine deaminase (ADA)

What accumulates in ADA deficiency?

Why does ADA deficiency mainly affect lymphocytes?

Why does ADA deficiency mainly affect lymphocytes?

How does dATP cause immunodeficiency?

dATP inhibits ribonucleotide reductase, blocking DNA synthesis → lymphocyte death

What type of immunodeficiency results from ADA deficiency?

Severe Combined Immunodeficiency (SCID) affecting B and T cells

How is ADA-SCID treated?

Enzyme replacement, bone marrow transplant, gene therapy, IVIG, isolation

What enzyme is deficient in PNP deficiency?

Purine nucleoside phosphorylase (PNP)

Which immune cells are mainly affected in PNP deficiency?

T cells (B cells relatively preserved)

What metabolite accumulates in PNP deficiency?

dGTP, which inhibits ribonucleotide reductase

Clinical features of PNP deficiency?

T-cell immunodeficiency + neurological symptoms

What causes hyperuricaemia?

Overproduction or underexcretion of uric acid

What percentage of gout patients are overproducers of uric acid?

Only 15–25%; most have reduced renal excretion

Why does gout often affect the big toe first?

Lower temperature → urate crystal precipitation in peripheral joints

Why does alcohol trigger gout attacks?

Increases urate production and reduces renal excretion

What are tophi?

Deposits of urate crystals in soft tissues (e.g. ear lobes)

How does allopurinol treat gout?

Inhibits xanthine oxidase, reducing uric acid production

What is febuxostat?

A non-purine xanthine oxidase inhibitor

What is the role of urate transporters (URAT1)?

Mediate renal reabsorption of uric acid

Why is purine metabolism linked to immunity?

Lymphocytes require rapid DNA synthesis → defects cause immunodeficiency

How does uric acid act as a danger signal?

Urate crystals are immunostimulatory and activate inflammation