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The Urea Cycle


Urea is the chief nitrogenous waste of mammals.
Most of our nitrogenous waste comes from the breakdown of amino acids.
This occurs by deamination.
Deamination of amino acids results in the production of ammonia (NH3).

Ammonia is an extremely toxic base and its accumulation in the body would
quickly be fatal.

However, the liver contains a system of carrier molecules and enzymes which quickly
converts the ammonia (and carbon dioxide) into urea.
This is called the urea cycle.
One turn of the cycle:

consumes 2 molecules of ammonia

consumes 1 molecule of carbon dioxide

creates 1 molecule of urea ((NH2)2CO

regenerates a molecule of ornithine for another turn.

Although our bodies cannot tolerate high concentrations of urea, it is much less poisonous
than ammonia.
Urea is removed efficiently by the kidneys.
Link to discussion of the
anatomy and physiology of the
kidneys.

What can go wrong?


There are several inherited diseases of the urea cycle caused by mutations in genes encoding
one or another of the necessary enzymes.

The most common of these is an inherited deficiency of ornithine transcarbamylase, an


enzyme needed for the conversion of ornithine to citrulline. It results in elevated levels of
ammonia that may be so high as to be life-threatening.
It is an X-linked disorder; therefore most commonly seen in males. It can be cured by a liver
transplant.
It can also be caused by a liver transplant! In 1998, an Austrian woman was given a new liver
from a male cadaver who unknown to the surgeons had a mutation in his single
ornithine transcarbamylase gene. The woman's blood level of ammonia shot up, and she died
a few days later.

Uric acid
Humans also excrete a second nitrogenous waste, uric acid. It is the product of nucleic acid,
not protein, metabolism. It is produced within peroxisomes.
Uric acid is only slightly soluble in water and easily precipitates out of solution
forming needlelike crystals of sodium urate. These

contribute to the formation of kidney stones;

produce the excruciating pain of gout when deposited in the joints.

Curiously, our kidneys reclaim most of the uric acid filtered at the glomeruli. Why, if it can
cause problems?

Uric acid is a potent antioxidant and thus can protect cells from damage
by reactive oxygen species (ROS). [Link]

The concentration of uric acid is 100-times greater in the cytosol than in


the extracellular fluid. So when lethally-damaged cells release their
contents, crystals of uric acid form in the vicinity. These enhance the
ability of nearby dendritic cells to "present" any antigens released at the
same time to T cells leading to a stronger immune response.

So the risk of kidney stones and gout may be the price we pay for these
protections.

Most mammals have an enzyme uricase for breaking uric acid down into a soluble
product. However, during the evolution of great apes and humans, the gene encoding uricase
became inactive. A predisposition to gout is our legacy.
Uric acid is the chief nitrogenous waste of

insects

lizards and snakes

birds

(It is the whitish material that birds leave on statues.)


These animals convert the waste products of protein metabolism as well as
nucleic acid metabolism into uric acid.

Because of its low solubility in water, these animals are able to eliminate waste nitrogen with
little loss of water.

http://www.labtestsonline.org.uk/understanding/analytes/urea/sample.html
Urea Test

Also known as: BUN (Blood Urea Nitrogen) Test


Related tests: Creatinine; Urinalysis

At a Glance

Test Sample

The Test

Common Questions

Links

The Test Sample


What is being tested?
Urea is produced when protein is broken down by the body. Nitrogen in the form
of ammonia is produced in the liver when protein is broken down. The nitrogen
combines with other chemicals in the liver to form the waste product urea. The
urea is released into the bloodstream and carried to the kidneys where it is
filtered out of the blood and excreted in the urine. Healthy kidneys remove more
than 90% of the urea the body produces, so blood levels can show how well your
kidneys are working.
Most diseases that affect the kidneys or liver can affect the amount of urea
present in the blood. If increased amounts of urea are produced by the liver or
decreased amounts are removed by the kidneys then blood urea concentrations
will rise. If significant liver damage or disease reduces the production of urea
then urea concentrations may fall.

How is the sample collected for testing?


A blood sample is taken from a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious,
embarrassed, or even difficult to manage, you might consider reading one or more of the
following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing,
Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through
Their Medical Tests.

http://www.tpub.com/content/armymedical/MD0579/MD0
5790017.htm
1-7.
URINE
Urine is a by-product of the kidney's activity. Volume, pH, and solute
concentration vary with the needs of the body's internal environment in a healthy
person. The characteristics of urine may change greatly when a person is ill. It is
possible to find out a great deal about the state of a body by analyzing the volume,
physical properties, and chemical properties of urine.
a. Physical Characteristics. Normal urine is yellow or amber colored and
transparent. The color, caused by pigments from the metabolism of bile, can change
because
of medication or diet. A person eats beets and his urine may be a reddish color.
An individual takes large amounts of vitamin C and his urine may be deep yellow for a
time. The odor of urine varies. Stale urine develops an ammonia odor (think of a
baby's diaper), but the urine that is expelled after the digestion of asparagus will have a
completely different, but characteristic, odor.
b. Composition. About 95 percent of the total volume of urine is water. The
other 5 percent is made up of solutes that come from cellular metabolism and outside
sources such as drugs. Included in the 5 percent are nitrogenous waste products,
electrolytes, toxins, and urea. Urea, an end product formed in the liver from protein
metabolism, is the chief nitrogenous waste product in the non-water portion of urine.
NOTE:
One of the screening tests for renal function is the blood urea nitrogen (BUN)
test. It is the most commonly ordered test. It measures blood levels of
nitrogen in urea. This test is not sensitive to mild degrees of renal
dysfunction, but it is a good clinical indication of significant renal dysfunction.
c. Specific Gravity. This is the ratio of the weight of a volume of a substance to
the weight of an equal volume of distilled water. The specific gravity of water is 1.000.
The specific gravity of urine depends on the amount of solid materials in the urine. The
specific gravity of normal urine ranges from 1.010 to 1.020. The greater the
concentration of solutes in the urine, the higher its specific gravity.
d. Amount Voided. A normal adult eliminates about 1500 cubic centimeters of
urine daily. The amount of urine voided depends on a number of factors: blood
pressure, blood concentration, diet, temperature, diuretics, mental state, and general
health.
e. Acidity/Alkalinity of Urine. Normal urine is slightly acid, but the acidity and
alkalinity of urine varies greatly with an individual's diet. A high-protein diet increases
the acidity of urine while a diet consisting of mostly vegetables increases the alkalinity of
urine. Other factors influencing urinary pH include high altitude, fasting, and exercise

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