Arginine and proline metabolism is one of the central pathways for the biosynthesis of the amino acids

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

and

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

from

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

. The pathways linking arginine, glutamate, and proline are bidirectional. Thus, the net utilization or production of these amino acids is highly dependent on cell type and developmental stage. Altered proline metabolism has been linked to metastasis formation in breast cancer.

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Proline is biosynthetically derived from the amino acid L-

Glutamate-5-semialdehyde Glutamate-5-semialdehyde is a non-proteinogenic amino acid involved in both the biosynthesis and degradation of proline and arginine (via ornithine), as well as in the biosynthesis of antibiotics, such as carbapenems. It is synthesized by the redu ...

is first formed by

glutamate 5-kinase In enzymology, a glutamate 5-kinase () is an enzyme that catalyzes the chemical reaction :ATP + L-glutamate \rightleftharpoons ADP + L-glutamate 5-phosphate Thus, the two substrates of this enzyme are ATP and L-glutamate, whereas its two prod ...

(ATP-dependent) and

glutamate-5-semialdehyde dehydrogenase In enzymology, a glutamate-5-semialdehyde dehydrogenase () is an enzyme that catalyzes the chemical reaction :L-glutamate 5-semialdehyde + phosphate + NADP+ \rightleftharpoons L-glutamyl 5-phosphate + NADPH + H+ The 3 substrates of this enzyme ...

(which requires NADH or NADPH). This can then either spontaneously cyclize to form

1-pyrroline-5-carboxylic acid 1-Pyrroline-5-carboxylic acid (systematic name 3,4-dihydro-2H-pyrrole-2-carboxylic acid) is a cyclic imino acid. Its conjugate base and anion is 1-pyrroline-5-carboxylate (P5C). In solution, P5C is in spontaneous equilibrium with glutamate-5-se ...

, which is reduced to proline by

pyrroline-5-carboxylate reductase In enzymology, a pyrroline-5-carboxylate reductase () is an enzyme that catalyzes the chemical reaction :L-proline + NAD(P)+ \rightleftharpoons 1-pyrroline-5-carboxylate + NAD(P)H + H+ The 3 substrates of this enzyme are L-proline, NAD+, and ...

(using NADH or NADPH), or turned into

ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...

ornithine aminotransferase Ornithine aminotransferase (OAT) is an enzyme which is encoded in human by the OAT gene located on chromosome 10. The OAT involved in the ultimate formation of the non-essential amino acid proline from the amino acid ornithine. Ornithine aminot ...

, followed by cyclisation by

ornithine cyclodeaminase The enzyme ornithine cyclodeaminase (EC 4.3.1.12) catalyzes the chemical reaction L-ornithine \rightleftharpoons L-proline + NH4+ This enzyme belongs to the family of lyases, specifically ammonia lyases, which cleave carbon-nitrogen bonds. Th ...

to form proline..

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 1 ...

is made from

and

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 syn ...

ornithine carbamoyltransferase 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 OT ...

. Arginine is then synthesized from citrulline 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 ...

by the sequential action of the cytosolic enzymes

argininosuccinate synthetase Argininosuccinate synthase or synthetase (ASS; ) is an enzyme that catalyzes the synthesis of argininosuccinic acid, argininosuccinate from citrulline and aspartic acid, aspartate. In humans, argininosuccinate synthase is encoded by the ''ASS ...

(ASS) and

argininosuccinate lyase The enzyme argininosuccinate lyase (EC 4.3.2.1, ASL, argininosuccinase; systematic name 2-(''N'' ω-L-arginino)succinate arginine-lyase (fumarate-forming)) catalyzes the reversible breakdown of argininosuccinate: :2-(''N'' ω-L-arginino)succina ...

(ASL).

References

{{reflist Proteinogenic amino acids Basic amino acids