Ornithine Lactamization
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Ornithine is a non-proteinogenic α-amino acid that plays a role in the
urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highl ...
. It is not incorporated into proteins during translation. Ornithine is abnormally accumulated in the body in
ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder, is the final enzyme in the proximal portion of the urea cycle, r ...
, a disorder of the urea cycle. The
moiety Moiety may refer to: __NOTOC__ Anthropology * Moiety (kinship), either of two groups into which a society is divided ** A division of society in the Iroquois societal structure in North America ** An Australian Aboriginal kinship group ** Native Ha ...
derived from ornithine is called ornithyl.


Role in urea cycle

L-Ornithine is one of the products of the action of the enzyme
arginase Arginase (, ''arginine amidinase'', ''canavanase'', ''L-arginase'', ''arginine transamidinase'') is a manganese-containing enzyme. The reaction catalyzed by this enzyme is: : arginine + H2O → ornithine + urea It is the final enzyme of the ur ...
on L-
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
, creating
urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...
. Therefore, ornithine is a central component of the
urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highl ...
, which enables the disposal of excess
nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
. Ornithine itself is recycled and, in a sense, acts as a catalyst. First, ammonia is converted into
carbamoyl phosphate Carbamoyl phosphate is an anion of biochemical significance. In land-dwelling animals, it is an intermediary metabolite in nitrogen disposal through the urea cycle and the synthesis of pyrimidines. Its enzymatic counterpart, carbamoyl phosphate sy ...
() by
carbamoyl phosphate synthetase Carbamoyl phosphate synthetase catalyzes the ATP-dependent synthesis of carbamoyl phosphate from glutamine () or ammonia () and bicarbonate. This ATP-grasp enzyme catalyzes the reaction of Adenosine triphosphate, ATP and bicarbonate to produc ...
.
Ornithine transcarbamylase Ornithine transcarbamylase (OTC) (also called ornithine carbamoyltransferase) is an enzyme () that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (Pi). There are two classes of O ...
then catalyzes the reaction between carbamoyl phosphate and ornithine to form
citrulline The organic compound citrulline is an α-amino acid. Its name is derived from '' citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in ...
and phosphate (Pi). Another
amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
is contributed by
aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protein ...
, leading to the formation of arginine and the byproduct
fumarate Fumaric acid or ''trans''-butenedioic acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297. The sa ...
. The resulting arginine, a
guanidinium Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...
compound, is subsequently hydrolyzed by arginase to regenerate ornithine and release urea. The two nitrogen atoms in urea are derived from ammonia and aspartate, while the nitrogen atoms in ornithine remain unchanged. Ornithine is not an amino acid directly coded for by
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
; that is, it is not a
proteinogenic amino acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation from RNA. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) ...
. However, in mammalian non-hepatic tissues, the primary role of the urea cycle is often the biosynthesis of arginine. As an intermediate in metabolic pathways, ornithine is thus quite important.


Other reactions

Ornithine, through the action of
ornithine decarboxylase The enzyme ornithine decarboxylase (, ODC) catalyzes the decarboxylation of ornithine (a product of the urea cycle) to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids ...
(EC 4.1.1.17), serves as the starting point for the synthesis of
polyamines A polyamine is an organic compound having two or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, Hygroscopy, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium de ...
such as
putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of Putrefaction, putref ...
. In bacteria such as ''
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'', ornithine can be synthesized from L-glutamate.


Research


Exercise fatigue

L-Ornithine supplementation has been shown to attenuate fatigue in subjects in placebo-controlled studies using a cycle ergometer. The results suggest that L-ornithine may exert an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia.


Weightlifting supplement

Amino acid supplements, including L-ornithine, are frequently marketed to bodybuilders and weightlifters with claims of increasing levels of
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
(HGH), muscle mass, and strength. A short, four-day clinical study conducted in 1993 reported that L-ornithine, in combination with L-arginine and L-lysine at 2 g/day each, did not increase HGH levels. A review published in 2002 concluded, "The use of specific amino acids to stimulate GH release by athletes is not recommended."


Cirrhosis

L-ornithine L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, has been used in the treatment of
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
and
hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stag ...
.


See also

*
Bisorcic Bisorcic (), also known as ''N''2,''N''5-diacetyl-L-ornithine, is a drug described as a hepatoprotective agent and "psychostimulant" which has been used in France in the treatment of asthenia. It is the ''N''2,''N''5- diacetylated derivative of ...
*
3-Methylornithine 3-Methylornithine is an amino acid with the formula H2N(CH2)2CH(CH3)CH(NH2)CO2H. This amino acid contains two stereogenic centers, but only one stereoisomer (namely (3''R'')-3-methyl-D-ornithine) occurs in nature. It is produced from lysine by th ...


References


External links


Ornithine mass Spectrum
{{Non-proteinogenic amino acids Alpha-Amino acids Basic amino acids Urea cycle Diamines Non-proteinogenic amino acids