TUGAS VALIDASI

VALIDASI METODE DEOKSIRIBOSA

SEBAGAI UJI PENANGKAPAN RADIKAL HIDROKSIL
OLEH VITAMIN C SECARA IN VITRO

OLEH:
DIENA RIFA’AH AMALIAH
N11107032

FAKULTAS FARMASI

UNIVERSITAS HASANUDDIN

MAKASSAR

2010
Arachidonic acid
From Wikipedia, the free encyclopedia

Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6). It
is the counterpart to the saturated arachidic acid found in peanut oil, (L. arachis – peanut.)[1]

Chemistry

In chemical structure, arachidonic acid is a carboxylic acid with a 20-carbon chain and four cis
double bonds; the first double bond is located at the sixth carbon from the omega end.

Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids.
However, almost all writings in biology, medicine and nutrition limit the term to all-cis
5,8,11,14-eicosatetraenoic acid.

Biology
Arachidonic acid is a polyunsaturated fatty acid that is present in the phospholipids (especially
phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositides) of membranes of the
body's cells, and is abundant in the brain and muscles.

In addition to being involved in cellular signaling as a lipid second messenger involved in the
regulation of signaling enzymes, such as PLC-γ, PLC-δ and PKC-α, -β and -γ isoforms,
arachidonic acid is a key inflammatory intermediate.[2] (Note separate synthetic pathways, as
described in section below)

Essential fatty acid

Arachidonic acid in the human body usually comes from dietary animal sources—meat, eggs,
dairy—or is synthesized from linoleic acid.

Arachidonic acid is one of the essential fatty acids required by most mammals. Some mammals
lack the ability to—or have a very limited capacity to—convert linoleic acid into arachidonic
acid, making it an essential part of their diet. Since little or no arachidonic acid is found in
common plants, such animals are obligate carnivores; the cat is a common example.[3][4] A
commercial source of arachidonic acid has been derived, however, from the fungus Mortierella
alpina [5]
Synthesis and cascade

Eicosanoid synthesis.

Arachidonic acid is freed from a phospholipid molecule by the enzyme phospholipase A2

(PLA2), which cleaves off the fatty acid, but can also be generated from DAG by Diacylglycerol
lipase.[2]

Arachidonic acid generated for signaling purposes appears to be derived by the action of a
phosphatidylcholine-specific cytosolic phospholipase A2 (cPLA2, 85 kDa), whereas
inflammatory arachidonic acid is generated by the action of a low-molecular-weight secretory
PLA2 (sPLA2, 14-18 kDa).[2]

Arachidonic acid is a precursor in the production of eicosanoids:

 the enzymes cyclooxygenase and peroxidase lead to Prostaglandin H2, which in turn is
used to produce the prostaglandins, prostacyclin, and thromboxanes.
 the enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the
leukotrienes.
 arachidonic acid is also used in the biosynthesis of anandamide.
 some arachidonic acid is converted into hydroxyeicosatetraenoic acids (HETEs) and
epoxyeicosatrienoic acids (EETs) by epoxygenase.[6]

The production of these derivatives and their action in the body are collectively known as the
arachidonic acid cascade; see essential fatty acid interactions for more details.

PLA2 activation

Further information: Phospholipase_A2#Regulation

PLA2, in turn, is activated by ligand binding to receptors, including:

 5-HT2 receptors [7]

 mGLUR1[7]
 bFGF receptor[7]
 INF-α receptor[7]
 INF-γ receptor[7]

Furthermore, any agent increasing intracellular calcium may cause activation of some forms of
PLA2.[8]

PLC activation

Further information: Phospholipase C#Activation

Alternatively, arachidonic acid may be cleaved from phospholipid by phospholipase C (PLC),

yielding diacylglycerol (DAG), which subsequently is cleaved by DAG lipase to yield
arachidonic acid.[7]

Receptors that activate this pathway include:

 A1 receptor[8]
 D2 receptor[8]
 α-2 adrenergic receptor[8]
 5-HT1 receptor[8]

PLC may also be activated by MAP kinase. Activators of this pathway include PDGF and FGF.[8]

Arachidonic acid in the body

Muscle growth

Through its conversion to active components such as the prostaglandin PGF2alpha, arachidonic
acid is necessary for the repair and growth of skeletal muscle tissue.[9] This role makes ARA an
important dietary component in support of the muscle anabolic process. One of the lead
researchers of the Baylor study (see Bodybuilding section) on arachidonic acid, Mike Roberts
MS, CSCS, has authored an article published under the title Arachidonic Acid, The New Mass
Builder explaining the role of this nutrient in muscle anabolism, and its potential for the
enhancement of muscle size and strength.[10] The paper explains that for optimal muscle growth a
training stimulus must elicit localized inflammation and soreness. It explains that arachidonic
acid (AA, 20:4n-6) is an essential Omega-6 (1-6) polyunsaturated fatty acid that is abundant in
skeletal muscle membrane phospholipids (figure 2). It is also the body's principal building block
for the production of prostaglandins, which are known to have various physiological roles
including a close involvement in inflammation. Also, the prostaglandin isomer PGF2a has a
potent ability to stimulate muscle growth. As such, arachidonic acid is a regulator of localized
muscle inflammation, and may be a central nutrient controlling the intensity of the
anabolic/tissue-rebuilding response to weight training.

Brain

Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in similar
quantities to DHA (docosahexaenoic acid). The two account for approximately 20% of its fatty
acid content.[11] Like DHA, neurological health is reliant upon sufficient levels of arachidonic
acid. Among other things, arachidonic acid helps to maintain hippocampal cell membrane
fluidity.[12] It also helps protect the brain from oxidative stress by activating perioxisomal
proliferator-activated receptor-y.[13] ARA also activates syntaxin-3 (STX-3), a protein involved in
the growth and repair of neurons.[14]

Arachidonic acid is also involved in early neurological development. In one study funded by the
U.S. National Institute of Child Health and Human Development, infants (18 months) given
supplemental arachidonic acid for 17 weeks demonstrated significant improvements in
intelligence, as measured by the Mental Development Index (MDI).[15] This effect is further
enhanced by the simultaneous supplementation of ARA with DHA.

In adults, the disturbed metabolism of ARA may be associated with neurological disorders such
as Alzheimer’s Disease and Bipolar Disorder.[16] This may involve significant alterations in the
conversion of arachidonic acid to other bioactive molecules (overexpression or disturbances in
the ARA enzyme cascade). It is of note that the dietary arachidonic acid consumption is not
associated with the onset of Alzheimer's disease, and studies suggest that the supplementation of
arachidonic acid during the early stages of this disease may actually be effective in reducing
symptoms and slowing the disease progress.[17] Additional studies on the supplementation of
arachidonic acid with Alzheimer's are needed.

Bodybuilding supplement

Arachidonic acid is marketed as an anabolic bodybuilding supplement in a variety of products.

The first clinical study concerning the use of arachidonic acid as a sport supplement was
conducted at Baylor University and published in the Journal of the International Society of
Sports Nutrition.[18]

The performance data results from the paper include the following statistically significant
improvement, and statistically strong trends:

A significant group × time interaction for relative Wingate peak power was observed among
groups (P = 0.02) with gains in peak power being significantly greater in the AA group (0.3 ± 1.2
W·kg-1) vs. PLA (0.2 ± 0.7 W·kg-1, Figure 1). Using repeated measures ANOVA with delta
scores, AA experienced significantly greater increases in comparison to the PLA group at day 50
(P < 0.05). Statistical trends were seen in Wingate total work (AA: 1,292 ± 1,206 vs. PLA: 510 ±
1,249 J, P = 0.09, ηp 2 = 0.052), favoring the AA group.
With regard to inflammation, the paper reported a statistically significant reduction in resting IL-
6 levels (a central regulator of inflammation):

IL-6 levels experienced a significant group × time interaction (P = 0.04) among groups with
subsequent post-hoc analyses revealing that IL-6 was significantly lower at day 25 of the study.
One way ANOVA of IL-6 delta values at day 25 revealed significantly greater increases in PLA
when compared to AA group (AA: 0.8 ± 13.5 pg·ml-1 vs. PLA: 52.5 ± 1.6 pg·ml-1, P = 0.01;
Figure 2)

Arachidonic acid was shown to improve peak muscle power, reduce resting IL-6 levels, and
produce statistically strong trends of improvements in muscle endurance, average power, and
bench press 1-rep maximum lift. This study provides preliminary evidence supporting the use of
arachidonic acid in sports nutrition. Further research is needed.

Dietary arachidonic acid and inflammation

Under normal metabolic conditions, the increased consumption of arachidonic acid is unlikely to
increase inflammation. ARA is metabolized to both pro-inflammatory and anti-inflammatory
molecules.[19] Studies giving between 840 mg and 2,000 mg per day to healthy individuals for up
to 50 days have shown no increases in inflammation or related metabolic activities.[19][20][21][22]
Increased arachidonic acid levels are actually associated with reduced pro-inflammatory IL-6
and IL-1 levels, and increased anti-inflammatory tumor-necrosis factor-beta.[23] This may result
in a reduction in systemic inflammation.

Arachidonic acid does still play a central role in inflammation related to injury and many
diseased states. How it is metabolized in the body dictates its inflammatory or anti-inflammatory
activity. Individuals suffering from joint pains or active inflammatory disease may find that
increased arachidonic acid consumption exacerbates symptoms, probably because it is being
more readily converted to inflammatory compounds. Likewise, high arachidonic acid
consumption is not advised for individuals with a history of inflammatory disease, or that are in
compromised health. It is also of note that while ARA supplementation does not appear to have
pro-inflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of
omega-3 EFA supplementation.[24]

Health effects of arachidonic acid supplementation

Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg for 50 days has been well
tolerated during several clinical studies, with no significant side effects reported. All common
markers of health including kidney and liver function,[21] serum lipids,[25] immunity,[26] and
platelet aggregation[20] appear to be unaffected with this level and duration of use. Furthermore,
higher concentrations of ARA in muscle tissue may be correlated with improved insulin
sensitivity.[27] Arachidonic acid supplementation by healthy adults appears to offer no toxicity or
significant safety risk.
A scientific advisory from the American Heart Association has favorably evaluated the health
impact of dietary Omega-6 fats, including arachidonic acid.[28] The group does not recommend
limiting this EFA. In fact, the paper recommends individuals follow a diet that consists of at least
5-10% of calories coming from omega-6 fats, including arachidonic acid. Dietary ARA is not a
risk factor for heart disease, and may play a role in maintaining optimal metabolism and reduced
heart disease risk. It is, therefore, recommended to maintain sufficient intake levels of both
omega 3 and omega 6 essential fatty acids for optimal health.

Arachidonic acid is not carcinogenic, and studies show the dietary level is not associated with an
increased risk of cancers.[29][30][31][32] ARA remains integral to the inflammatory and cell growth
process, however, which is disturbed in many types of disease including cancer. Therefore, the
safety of arachidonic acid supplementation in patients suffering from cancer, inflammatory, or
other diseased states is unknown, and supplementation is not recommended.
 TUGAS VALIDASI

VALIDASI METODE PENETAPAN KADAR ASAM ASETILSALISILAT DALAM

SEDIAAN OBAT MEMANFAATKAN SINAR REFLEKTAN TERUKUR DARI BERCAK
YANG DIHASILKAN

OLEH:
NIRWANA SARI
N11107032

FAKULTAS FARMASI

UNIVERSITAS HASANUDDIN

MAKASSAR

2010