1557_L1-2Notes_NucleotideMetab-Disease-Bjork_2024

They competitively inhibit dihydropteroate synthase to decrease folic acid synthesis in bacteria.

Underexcretion of uric acid.

Overproduction of uric acid.

X-linked PRPP synthetase overactivity mutations.

2’-deoxy ribonucleotides (dNTPs).

Inosine monophosphate (IMP).

Orotic aciduria.

Thymidylate synthase.

A nucleotide or nucleoside phosphate (mono-, di-, or tri-phosphate).

They decrease the binding affinity of the enzyme to its substrate.

It is converted to oxypurinol, which competitively inhibits xanthine oxidase, decreasing uric acid synthesis.

Purine-rich foods such as fish, red meat, and beer.

A nitrogenous base, a pentose monosaccharide (sugar), and 1-3 phosphate groups.

Chronic hyperuricemia with intermittent acute attacks of inflammation or chronic arthritis.

It is recently approved for long-term treatment of gout.

Antibiotics, such as sulfonamide drugs and trimethoprim.

Hair loss, nausea, and vomiting due to toxicity in rapidly dividing normal cells.

It is often used for the prevention of tumor lysis syndrome.

IMP is a branch point that can be converted to either AMP or GMP as needed.

As end-product inhibitors, they can inhibit their own synthesis and influence the conversion of IMP.

They phosphorylate nucleosides to nucleotides using ATP as an energy source.

It requires less energy expenditure.

Inflammation occurs in the joint, causing swelling, warmth, redness, and tenderness.

1-2 times per year and often affect only one joint.

Less than 6 mg/dL.

They increase the binding affinity of the enzyme to its substrate.

It inhibits uric acid synthesis and is effective in reducing SUA levels in both overproducers and underexcretors.

They are converted to uric acid, which enters the blood and is excreted by the kidneys.

Indomethacin, NSAIDs, steroids (e.g., prednisone), and colchicine.

PRPP.

Converts IMP and GMP to their nucleoside forms.

It competitively inhibits DHF reductase, depleting THF and inhibiting nucleotide synthesis in human cells.

It inhibits its own synthesis, leading to more IMP being converted to GMP.

It is an immunosuppressant used in organ transplants to prevent graft rejection.

End-product inhibitors (negative allosteric effectors).

ATP for energy and the stepwise addition of individual atoms from amino acids, CO2, and N10-formyltetrahydrofolate.

Suddenly at night or early morning under conditions favoring decreased solubility of uric acid.

Hypoxanthine.

If SUA is still greater than approximately 7 mg/dL after managing the acute attack.

Hyperuricemia causing accumulation of MSU crystals, resulting in multiple severe attacks.

It converts Adenine to AMP irreversibly.

Formation of uric acid stones, gouty arthritis, motor dysfunction, cognitive deficits, and behavioral disturbances.

Carbamoyl phosphate synthetase (CPS) II.

Deficiencies of ADA and PNP.

Reducing pain and inflammation by administering Indomethacin.

Uridine 5’-monophosphate (UMP).

Aspartate (Asp), Glycine (Gly), and Glutamine (Gln).

PRPP synthetase.

Ribose 5-phosphate.

A condition where 50% of gout attacks affect the first metatarsophalangeal joint of the big toe.

Formation of uric acid stones in the kidney.

Age, sex, diet, overweight/obesity, and certain drugs.

ATP (adenosine triphosphate).

Nucleotides act as carriers of activated intermediates, such as UDP-glucose in glycogen synthesis.

Hypoxanthine and Guanine, respectively.

In the liver.

It inhibits thymidylate synthase during thymidine nucleotide synthesis as a 'suicide' inhibitor.

PRPP (5-phosphoribosyl-1-pyrophosphate).

PRPP is the 'activated' ribose 5-phosphate donor for both purine biosynthesis and salvage, as well as pyrimidine biosynthesis.

It is activated by inorganic phosphate (Pi) and ATP, and regulated through end-product inhibition by purine nucleotide end-products.

Allosteric regulation.

Deoxyribonucleoside triphosphates such as dATP, dGTP, dCTP, and dTTP.

They are denatured in the stomach and digested in the small intestine by pancreatic enzymes.

It allows purine nucleotides to be produced with lower energy requirements using de novo synthesized bases and nucleosides from the liver.

Lower SUA levels using uric acid lowering therapy (UALT) approaches.

Uric acid.

Only up to a third.

ATP and glutamine.

Kidney disease, age-related decrease in kidney filtration rate, heart disease, genetic predisposition, and environmental factors.

Synthesis of 5’-phosphoribosylamine.

β-alanine, β-aminoisobutyrate, NH3, and CO2.

Lesch-Nyhan syndrome (LNS).

It reduces the 2’-OH group of NDPs to produce dNDPs using NADPH.

Failure to thrive and megaloblastic anemia.

Through a series of kinase reactions.

Nucleic acids.

Probenecid and Sulfinpyrazone.

By visualizing needle-shaped monosodium urate crystals in synovial fluid using light microscopy.

Pain and inflammation, without attempting to lower SUA levels.

A nucleoside consists of a pentose sugar and a base, while a nucleotide includes a pentose sugar, a base, and one or more phosphate groups.

Ribonucleosides contain ribose sugar, while deoxyribonucleosides contain 2-deoxyribose sugar.

Above 3.4-7.0 mg/dL.

It converts uric acid to allantoin, which is more soluble.

An adequate supply of nucleotides.

In all tissues.

It depletes cellular dNTP levels required for cell division by inhibiting ribonucleotide reductase.

UMP synthase.

From UDP, dCTP, or dCMP.

UMP, dCTP or dCMP → dUMP → dTMP → dTTP.

RNA synthesis.

A mass comprised of MSU crystals that forms in soft tissues, often in extremities.

Febuxostat is a non-purine inhibitor of xanthine oxidase that non-competitively blocks the enzyme’s active site; it may be more effective in some patients than Allopurinol.

Nucleotides are essential for energy currency (ATP), production of RNA and DNA, carriers of activated intermediates, second messengers in signal transduction, and enzyme regulation.

UTP via end-product inhibition.

Urate oxidase (uricase).

Due to high levels of cell death and subsequent increase in availability of nucleotides.

GTP and aspartate.

Ribonucleotide reductase.

Localized inflammatory response and formation of monosodium urate (MSU) crystals.

ATP.

The asymptomatic period of approximately 2 weeks following an acute gout attack.

They are one-carbon donors and coenzymes in many enzymatic reactions.

They competitively inhibit reabsorption of uric acid by kidney tubules, increasing its excretion in urine.

Offal, red meat, poultry, seafood, yeast, mushrooms, and non-distilled alcoholic beverages, especially beer.

The cytoplasm of liver hepatocytes.

It reduces gout-induced inflammation by preventing microtubule formation.

cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate).

Purine salvage.

Base-specific and general nucleoside kinases.

Orotic acid (orotate).

From ribonucleoside diphosphates (NDPs) via ribonucleotide reductase during S-phase of the cell cycle.

Carbon and Nitrogen atoms from Gln, Gly, and Asp amino acids.

N10-formyltetrahydrofolate (folic acid derivative).

Resolubilization of monosodium urate crystals can cause episodic SUA elevations.

Adequate protein/amino acid and vitamin intake (e.g., folic acid).

Impaired purine salvage due to HGPRT deficiency.

The pyrimidine base is synthesized before ribose 5-phosphate is attached.

DNA contains A, G, C, and T; RNA contains A, G, C, and U (uracil replaces thymine).

IMP or Adenosine to Inosine.

It inhibits its own synthesis, leading to more IMP being converted to AMP.

It is responsible for the effectiveness of uridine as a treatment for orotic aciduria.

A process that reutilizes free purine bases derived from nucleic acids to convert them into nucleoside triphosphates.

ATP activates it, while dATP inhibits it.

Administration of exogenous uridine nucleoside.

Converts UTP to CTP by adding an amino group from glutamine.

Ribonucleoside triphosphates such as ATP, GTP, CTP, and UTP.

It catalyzes the irreversible conversion of Hypoxanthine to IMP and Guanine to GMP.

Increased PRPP levels and decreased IMP and GMP levels, leading to excessive de novo purine production.

Synthesis of carbamoyl phosphate.

Coenzyme A, FAD, NAD+, and NADP+.

Oxidizes Hypoxanthine to Xanthine and then to uric acid.