Purine and Uric Acid Metabolism Flashcards
Describe uric acid
Poorly soluble in plasma
Lower the pH the less soluble it becomes
Uric acid reversible reaction to urate releasing proton
Comes from the breakdown of purines (e.g. A, G)
Name the purines
Adenine
Guanine
Hypoxanthine
Xanthine
What is the source of purines
Diet
Breakdown of nucleotides from tissues
Synthesis in the body
How does uric acid leave the body
Excreted in urine (predominately)
Breakdown in the gut (small amount)
Describe gout
High uric acid levels in the blood cause urate/uric acid crystals to deposit in joint
The crystals cause inflammation, which then causes the swelling, pain and redness
What is uric acid balance
Production/intake vs. excretion
Explain purine metabolism
Purine synthesis + dietary purines + tissue nucleotides = body purine nucleotides
= purines to uric acid (end product) to excretion
What are forms of dietary purines
Meat
Offal - heart, liver and kidney
Seafood - muscles
Fish - herring and sardines
Oatmeal, soya and yeast extracts
Fructose - found in soft drinks
What can lead to reduced excretion
Reduced kidney function
Risk of gout
Metabolic syndrome
- obesity
- raised triglycerides
- raised blood pressure
Coronary heart disease
Diabetes
What are complications of high uric acid
Kidney stones
- urate crystals can form in the kidneys
- cause damage to the kidneys and reduces kidney function
Gout
Gouty tophi - urate crystals deposited in the soft tissue
What does purine metabolism include
De novo synthesis
Recycling pathways
What is uric acid
Metabolic end product of purine metabolism
Define hyperuricemia
Due to over-production or under-excretion of uric acid or due to a combination
What are the most commonly affected joints from gout
Big toe
What are the most commonly affected joints from gout
Big toe
Why are do less women get gout
Oestrogen is protective - helps the excretion of uric acid
What is the method of uric acid formation
Key enzyme - xanthine oxidase (each step uses this)
Purines - xanthine - uric acid
What is the main enzyme in uric acid formation
Xanthine oxidase
What is the role of rasburicase
Uric acid is converted to allantoin by raburicase (recombinant form of urate-oxidase)
How does purine get converted back into body purine nucleotides
Hypoxanthine and guanine are recycled back to precursors by enzyme HPRT
If enzyme is missing leads to an increased production of uric acid
Enzyme - hypoxanthine-guanine phosphoribosyl transferase
What is the range of normal uric acid
Men 200-430 umol/L
Women 140-360 umol/L
