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Uric Acid
Information
Uric acid (or urate) is an organic compound of
carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3.
Metabolic processes
Xanthine oxidase oxidizes oxypurines such as xanthine and
hypoxanthine to uric acid. In humans and higher primates, uric acid
is the final oxidation product of purine catabolism. In most other
mammals, the enzyme uricase further oxidizes uric acid to allantoin.[2]
The loss of uricase in higher primates parallels the similar loss of
the ability to synthesize ascorbic acid.[3] Both urate and ascorbate
are strong reducing agents (electron donors) and potent
antioxidants. In humans, about half the antioxidant capacity of
plasma comes from uric acid.
Uric acid is also the end product of nitrogen catabolism in birds
and reptiles. In such species, it is excreted in feces as a dry
mass. While this compound is produced through a complex and
energetically costly metabolic pathway (in comparison to other
nitrogenated wastes such as urea or ammonia), its elimination
minimizes water loss. It is therefore commonly found in the
excretions of animals—such as the kangaroo rat—that live in very dry
environments. The Dalmatian dog has a defect in uric acid uptake by
liver, resulting in decreased conversion to allantoin, so this breed
excretes uric acid, and not allantoin, in the urine.
Medical issues
Humans produce large quantities of uric acid. In human blood, uric
acid concentrations between 3.6 mg/dL (~214µmol/L) and 8.3 mg/dL
(~494µmol/L) (1mg/dL=59.48 µmol/L)[4] are considered normal by the
American Medical Association, although significantly lower levels
are common in vegetarians due to a decreased intake of purine-rich
meat.[5]
High uric acid
Gout
Excess serum accumulation of uric acid can lead to a type of
arthritis known as gout.[6]
Elevated serum uric acid (hyperuricemia) can result from high intake
of purine-rich foods, high fructose intake (regardless of fructose's
low Glycemic Index (GI) value) and/or impaired excretion by the
kidneys. Saturation levels of uric acid in blood may result in one
form of kidney stones when the urate crystallizes in the kidney.
These uric acid stones are radiolucent and so do not appear on an
abdominal x-ray. Their presence must be diagnosed by ultrasound for
this reason. Some patients with gout eventually get uric kidney
stones.
Gout can occur where serum uric acid levels are as low as 6 mg/dL
(~357µmol/L), but an individual can have serum values as high as 9.5
mg/dL (~565µmol/L) and not have gout[7] (no abstract available;
levels reported at [8]).
Lesch-Nyhan syndrome
Lesch-Nyhan syndrome, an extremely rare inherited disorder, is also
associated with very high serum uric acid levels.[9]
Spasticity, involuntary movement and cognitive retardation as well
as manifestations of gout are seen in cases of this syndrome.[10]
Cardiovascular disease
Although uric acid can act as an antioxidant, excess serum
accumulation is often associated with cardiovascular disease. It is
not known whether this is causative (e.g., by acting as a prooxidant
) or a protective reaction taking advantage of urate's antioxidant
properties. [11]
Diabetes
The association of high serum uric acid with insulin resistance has
been known since the early part of the 20th century, nevertheless,
recognition of high serum uric acid as a risk factor for diabetes
has been a matter of debate. In fact, hyperuricemia has always been
presumed to be a consequence of insulin resistance rather than its
precursor [12]. However, it was shown in a prospective follow-up
study that high serum uric acid is associated with higher risk of
type 2 diabetes independent of obesity, dyslipidemia, and
hypertension [13].
Metabolic syndrome
Hyperuricemia is associated with components of metabolic syndrome
and it has been debated for a while to be a component of it. It has
been shown in a recent study that fructose-induced hyperuricemia may
play a pathogenic role in the metabolic syndrome. This agrees with
the increased consumption of fructose-base drinks in recent decades
and the epidemic of diabetes and obesity [14].
Low uric acid
Multiple sclerosis
Lower serum values of uric acid have been associated with Multiple
Sclerosis. Multiple sclerosis (MS) patients have been found to have
serum levels ~194µmol/L, with patients in relapse averaging
~160µmol/L and patients in remission averaging ~230µmol/L. Serum
uric acid in healthy controls was ~290µmol/L.[15] Conversion factor:
1mg/dL=59.48 µmol/L[16]
A 1998 study completed a statistical analysis of 20 million patient
records, comparing serum uric acid values in patients with gout and
patients with multiple sclerosis. Almost no overlap between the
groups was found.[17]
Uric acid has been successfully used in the treatment and prevention
of the animal (murine) model of MS. A 2006 study found that
elevation of serum uric acid values in multiple sclerosis patients,
by oral supplementation with inosine, resulted in lower relapse
rates, and no adverse effects.[18]
Oxidative stress
Uric acid may be a marker of oxidative stress,[19] and may have a
potential therapeutic role as an antioxidant (PMID 16375736). On the
other hand, like other strong reducing substances such as ascorbate,
uric acid can also act as a prooxidant,[20] particularly at elevated
levels. Thus, it is unclear whether elevated levels of uric acid in
diseases associated with oxidative stress such as stroke and
atherosclerosis are a protective response or a primary cause.[21]
For example, some researchers propose that hyperuricemia-induced
oxidative stress is a cause of Metabolic syndrome.[22][23] On the
other hand, plasma uric acid levels correlate with longevity in
primates and other mammals.[24] This is presumably a function of
urate's antioxidant properties.
Sources of uric acid
In many instances, people have elevated uric acid levels for
hereditary reasons.
Diet may also be a factor.
Purines are found in high amounts in animal food products,
especially internal organs.[25]
Examples of high purine sources include: sweetbreads, anchovies,
sardines, liver, beef kidneys, brains, meat extracts (e.g Oxo,
Bovril), herring, mackerel, scallops, game meats, and gravy.
A moderate amount of purine is also contained in beef, pork,
poultry, fish and seafood, asparagus, cauliflower, spinach,
mushrooms, green peas, lentils, dried peas, beans, oatmeal, wheat
bran and wheat germ.[26]
Moderate intake of purine-containing food is not associated with an
increased risk of gout.[27]
Serum uric acid can be elevated due to high fructose intake [28],
reduced excretion by the kidneys, and or high intake of dietary
purine.
Fructose can be found in processed foods and soda beverages - in
some countries, in the form of high fructose corn syrup.
Causes of low uric acid
Aside from avoidance of purine foods, both accumulated copper and
low vitamin B2 can exacerbate low uric acid levels, which in turn is
hypothesized to lead to myelin degeneration seen in multiple
sclerosis.[29]
Other uric acid facts
The high nitrogen content of uric acid makes guano a useful
agricultural fertilizer.
The crystalline form of uric acid is used as a reflector in certain
species of fireflies.
The uric acid in urine can also dry in a baby's diaper to form a
pinkish powder that is harmless.
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