Metabolitos

Azealaic Acid

Azelaic acid (AZA) is a naturally occurring saturated nine-carbon dicarboxylic acid

(COOH (CH2)7-COOH). It possesses a variety of biological actions both in vitro and
in vivo. Interest in the biological activity of AZA arose originally out of studies of skin
surface lipids and the pathogenesis of hypochromia in pityriasis versicolor infection.
Later, it was shown that Pityrosporum can oxidize unsaturated fatty acids to C8-C12
dicarboxylic acids that are cornpetitive inhibitors of tyrosinase in vitro. Azelaic acid
was chosen for further investigation and development of a new topical drug for
treating hyperpigmentary disorders for the following reasons: it possesses a middle-
range of antityrosinase activity, is inexpensive, and more soluble to be incorporated
into a base cream than other dicarboxylic acids. Azelaic acid is another option for
the topical treatment of mild to moderate inflammatory acne vulgaris. It offers
effectiveness similar to that of other agents without the systemic side effects of oral
antibiotics or the allergic sensitization of topical benzoyl peroxide and with less
irritation than tretinoin. Azelaic acid is less expensive than certain other prescription
acne preparations, but it is much more expensive than nonprescription benzoyl
peroxide preparations. Whether it is safe and effective when used in combination
with other agents is not known. (PMID: 7737781 , 8961845 ).

glyceric acid
Glyceric acid is a colourless syrupy acid, obtained from oxidation of glycerol. It is a
compound that is secreted excessively in the urine by patients suffering from D-
glyceric aciduria, an inborn error of metabolism, and D-glycerate anemia. Deficiency
of human glycerate kinase leads to D-glycerate acidemia/D-glyceric aciduria.
Symptoms of the disease include progressive neurological impairment, hypotonia,
seizures, failure to thrive, and metabolic acidosis. At sufficiently high levels, glyceric
acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound
that induces acidosis, which has multiple adverse effects on many organ systems.
A metabotoxin is an endogenously produced metabolite that causes adverse health
effects at chronically high levels. Glyceric acid is an organic acid. Abnormally high
levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the
brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs
when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms
include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and
lack of energy (lethargy). These can progress to heart abnormalities, seizures, coma,
and possibly death. These are also the characteristic symptoms of untreated glyceric
aciduria. Many affected children with organic acidemias experience intellectual
disability or delayed development. In adults, acidosis or acidemia is characterized
by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.

Pseudouridine
Pseudouridine is the C-glycoside isomer of the nucleoside uridine, and it is the most
prevalent of the over one hundred different modified nucleosides found in RNA.
Pseudouridine is found in all species and in all classes of RNA except mRNA. It is
formed by enzymes called pseudouridine synthases, which post-transcriptionally
isomerize specific uridine residues in RNA (Wikipedia).
Disease: Canavan disease, colorectal cancer, epithelial ovarian cancer

5-hydroxyhexanoic acid
5-Hydroxyhexanoic acid is a normal dicarboxylic acid degradation product of fatty
acids; however, it has been found in patients with non-ketotic dicarboxylic aciduria
and one patient on a diet containing excessive amounts of medium-chain
triglycerides. Increased amounts of dicarboxylic acids are excreted in human urine
under conditions of medium-chain triglyceride (MCT) feeding, abnormal fatty acid
oxidation (FAO) and fasting. Criteria to distinguish dicarboxylic aciduria originating
from MCT feeding and other conditions are needed in urinary organic acid profiling
for detecting inborn errors of metabolism. Medium-chain triglycerides (MCTs) are
absorbed and metabolized differently from long-chain triglycerides (LCTs). MCTs
may be useful as a dietary substitute in a variety of clinical disorders. Urinary
excretion of 5-hydroxyhexanoic acid, the (omega-1) hydroxylation product, was
increased during MCT feeding as compared with LCT feeding in patients with non-
insulin-dependent diabetes mellitus (PMID: 6897376 , 2239769 , 8596483 ).
Moreover, 5-hydroxyhexanoic acid is also found to be associated with Medium chain
acyl-CoA dehydrogenase deficiency (MCADD), which is also an inborn error of
metabolism.

Tirosine
Tyrosine is an essential amino acid that readily passes the blood-brain barrier. Once
in the brain, it is a precursor for the neurotransmitters dopamine, norepinephrine and
epinephrine, better known as adrenalin. These neurotransmitters are an important
part of the body's sympathetic nervous system, and their concentrations in the body
and brain are directly dependent upon dietary tyrosine. Tyrosine is not found in large
concentrations throughout the body, probably because it is rapidly metabolized. Folic
acid, copper and vitamin C are cofactor nutrients of these reactions. Tyrosine is also
the precursor for hormones, thyroid, catecholestrogens and the major human
pigment, melanin. Tyrosine is an important amino acid in many proteins, peptides
and even enkephalins, the body's natural pain reliever. Valine and other branched
amino acids, and possibly tryptophan and phenylalanine may reduce tyrosine
absorption. A number of genetic errors of tyrosine metabolism occur, such as
hawkinsinuria and tyrosinemia I. Most common is the increased amount of tyrosine
in the blood of premature infants, which is marked by decreased motor activity,
lethargy and poor feeding. Infection and intellectual deficits may occur. Vitamin C
supplements reverse the disease. Some adults also develop elevated tyrosine in
their blood. This indicates a need for more vitamin C. More tyrosine is needed under
stress, and tyrosine supplements prevent the stress-induced depletion of
norepinephrine and can cure biochemical depression. However, tyrosine may not be
good for psychosis. Many antipsychotic medications apparently function by inhibiting
tyrosine metabolism. L-dopa, which is directly used in Parkinson's, is made from
tyrosine. Tyrosine, the nutrient, can be used as an adjunct in the treatment of
Parkinson's. Peripheral metabolism of tyrosine necessitates large doses of tyrosine,
however, compared to L-dopa (http://www.dcnutrition.com).

Phenylalanine

Phenylalanine is an essential amino acid and the precursor of the amino acid
tyrosine. Like tyrosine, phenylalanine is also a precursor for catecholamines
including tyramine, dopamine, epinephrine, and norepinephrine. Catecholamines
are neurotransmitters that act as adrenalin-like substances. Interestingly, several
psychotropic drugs (mescaline, morphine, codeine, and papaverine) also have
phenylalanine as a constituent. Phenylalanine is highly concentrated in the human
brain and plasma. Normal metabolism of phenylalanine requires biopterin, iron,
niacin, vitamin B6, copper, and vitamin C. An average adult ingests 5 g of
phenylalanine per day and may optimally need up to 8 g daily. Phenylalanine is
highly concentrated in a number of high protein foods, such as meat, cottage cheese,
and wheat germ. An additional dietary source of phenylalanine is artificial
sweeteners containing aspartame. As a general rule, aspartame should be avoided
by phenylketonurics and pregnant women. When present in sufficiently high levels,
phenylalanine can act as a neurotoxin and a metabotoxin. A neurotoxin is a
compound that disrupts or attacks neural cells and neural tissue. A metabotoxin is
an endogenously produced metabolite that causes adverse health effects at
chronically high levels. Chronically high levels of phenylalanine are associated with
at least five inborn errors of metabolism, including Hartnup disorder,
hyperphenylalaninemia due to guanosine triphosphate cyclohydrolase deficiency,
phenylketonuria (PKU), tyrosinemia type 2 (or Richner-Hanhart syndrome), and
tyrosinemia type III (TYRO3). Phenylketonurics have elevated serum plasma levels
of phenylalanine up to 400 times normal. High plasma concentrations of
phenylalanine influence the blood-brain barrier transport of large neutral amino
acids. The high plasma phenylalanine concentrations increase phenylalanine entry
into the brain and restrict the entry of other large neutral amino acids
(PMID: 19191004 ). Phenylalanine has been found to interfere with different cerebral
enzyme systems. Untreated phenylketonuria (PKU) can lead to intellectual disability,
seizures, behavioural problems, and mental disorders. It may also result in a musty
smell and lighter skin. Classic PKU dramatically affects myelination and white matter
tracts in untreated infants; this may be one major cause of neurological disorders
associated with phenylketonuria. Mild phenylketonuria can act as an unsuspected
cause of hyperactivity, learning problems, and other developmental problems in
children. It has been recently suggested that PKU may resemble amyloid diseases,
such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic
amyloid-like assemblies of phenylalanine (PMID: 22706200 ). Phenylalanine also
has some potential benefits. Phenylalanine can act as an effective pain reliever. Its
use in premenstrual syndrome and Parkinson's may enhance the effects of
acupuncture and electric transcutaneous nerve stimulation (TENS). Phenylalanine
and tyrosine, like L-DOPA, produce a catecholamine-like effect. Phenylalanine is
better absorbed than tyrosine and may cause fewer headaches. Low phenylalanine
diets have been prescribed for certain cancers with mixed results. For instance,
some tumours use more phenylalanine than others (particularly melatonin-producing
tumours called melanomas).

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