Alya Putri Khairani / 130110110220 /

C2

Uric Acid and Its Metabolism

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It
forms ions and salts known as Urates and Acid Urates such as Ammonium Acid Urate. Uric acid created when the
body breaks down substances called Purines. Purines are found in some foods and drinks, such as liver, anchovies,
mackerel, dried beans and peas and beer. Most Uric acid dissolves in blood and travels to the kidneys, where it
passes out in urine

PURINE CATABOLISM

Guanine nucleotides are hydrolyzed to the nucleoside Guanosine which undergoes phosphorolysis
to Guanine and ribose 1-P. Man's intracellular nucleotidases are not very active toward AMP, however.
Rather, AMP is deaminated by the enzyme Adenylate (AMP) Deaminase to IMP. In the catobilsm of purine
nucleotides, IMP is further degraded by hydrolysis with nucleotidase to Inosine and then phosphorolysis
to Hypoxanthine. Both adenine and guanine nucleotides converge at the common intermediate xanthine.
Hypoxanthine, representing the original adenine, is oxidized to xanthine by the enzyme Xanthine Oxidase.
Guanine is deaminated, with the amino group released as Ammonia, to Xanthine. If this process is occurring in
tissues other than liver, most of the Ammonia will be transported to the liver as Glutamine for ultimate excretion as
Urea. Xanthine, like hypoxanthine, is oxidized by oxygen and Xanthine oxidase with the production of hydrogen
peroxide. In man, the Urate is excreted and the hydrogen peroxide is degraded by catalase. Xanthine oxidase is
present in significant concentration only in liver and intestine. The pathway to the nucleosides, possibly to the free
bases, is present in many tissues

RELATED TO THE KIDNEY FUNCTION

Urate homeostasis depends on the balance between production and complex processes of secretion and
reabsorption in the kidney tubule and excretion in the intestine. It is estimated that approximately 30% of uric acid
excretion is by the intestine by mechanisms that have so far not been investigated in detail. In the human kidney,
urate handling involves urate glomerular filtration followed by a complex array of reabsorptive and secretory
mechanisms taking place in the proximal tubule.

Alya Putri Khairani / 130110110220 /

C2

Renal excretion of uric acid involves 4 pathways: filtration, reabsorption, secretion, and postsecretory reabsorption.
Urate is freely filtered at the glomerulus. An active anion-exchange process in the early proximal convoluted tubule
reabsorbs most of it. Most urinary uric acid appears to be derived from tubular secretion, possibly from the S2
segment of the proximal tubule. Overall, 98-100% of filtered urate is reabsorbed; 6-10% is secreted, ultimately
appearing in the final urine

Physiologically, the major factors that affect urate excretion are the tubular fluid pH, the tubular fluid flow rate, and
renal blood flow. The first 2 factors primarily diminish uric acid and urate precipitation in the collecting ducts, while
the third is important in urate secretion. In disorders such as sickle cell disease, hypertension, and eclampsia,
hyperuricemia out of proportion with decreases in glomerular filtration result from decreased renal blood flow.
Organic acids, such as lactic acid and ketoacids, also can impair the proximal secretion of uric acid

RELATED TO PAIN ON THE KNEE

The joint inflammation is precipitated by deposits of uric acid crystals in the joint fluid (synovial fluid) and joint
lining (synovial lining). Crystal deposits in the cartilage can cause cartilage degeneration. Intense joint
inflammation occurs as the immune system reacts, causing white blood cells to engulf the uric acid crystals and
chemical messengers of inflammation to be released, leading to pain, heat, and redness of the joint tissues. This is
normally occur in gout

In this case, cartilage begins to degenerate by flaking or forming tiny crevasses. In advanced osteoarthritis, there
is a total loss of the cartilage cushion between the bones of the joints. Repetitive use of the worn joints over the
years can irritate and inflame the cartilage, causing joint pain and swelling. This is happening in Primary
Osteoarthritis. Loss of the cartilage cushion causes friction between the bones, leading to pain and limitation of
joint mobility. Secondary osteoarthritis is a form of osteoarthritis that is caused by another disease or condition.
Conditions that can lead to secondary osteoarthritis include obesity, repeated trauma or surgery to the joint
structures, abnormal joints at birth (congenital abnormalities), gout, diabetes, and other hormone disorders.
Obesity causes osteoarthritis by increasing the mechanical stress on the joint and therefore on the cartilage. In
fact, next to aging, obesity is the most significant risk factor for osteoarthritis of the knees. The early development
of osteoarthritis of the knees among weight lifters is believed to be in part due to their high body weight. Repeated
trauma to joint tissues (ligaments, bones, and cartilage) is believed to lead to early osteoarthritis of the knees.

Alya Putri Khairani / 130110110220 /

C2
And in the end, due to the high levels of Uric Acid, the patient may have uric acid crystal in the knees that can
cause Gout. As we know that Gout is the predisposing factor for Osteoarthritis. So basically, there are 2
mechanisms that can occur in this case

References:
http://library.med.utah.edu/NetBiochem/pupyr/pp.htm
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001460/
http://www.medicinenet.com/osteoarthritis/article.htm
http://www.jci.org/articles/view/42344
http://www.medpath.info/MainContent/Skeletal/Joint_02.htm
l