Copeptin (also known as CT-proAVP) is a 39-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

-long

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

derived from the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

of pre-pro-hormone of arginine

vasopressin Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the ''AVP'' gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It ...

, and copeptin. Arginine vasopressin (AVP), also known as the antidiuretic hormone (ADH), is encoded by the AVP gene and is involved in multiple cardiovascular and renal pathways and abnormal level of AVP are associated with various diseases. Hence measurement of AVP would be useful, but is not commonly carried out in clinical practice because of its very short

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

making it difficult to quantify. In contrast, copeptin can be immunologically tested with ease and therefore can be used as a vasopressin surrogate marker.

Synthesis and secretion

Copeptin is a 39-

-long, glycosylated

. It is synthesized mainly in the paraventricular neurons of the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

and in the

supraoptic nucleus The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 ...

. During axonal transport, pre-pro-AVP is proteolytically cleaved into vasopressin, and copeptin. These molecules are then stored in secretory granules in the

posterior pituitary The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. Unlike the anterior pituitary, the posterior pituitary is not glandular, but largely a collection of axonal projec ...

and released upon osmotic or non-osmotic ( hemodynamical; stress-related) stimuli.

Function

Once secreted into the bloodstream, there is no known biological role for copeptin. However, when pre-pro-vasopressin is processed during the axonal transport, copeptin may contribute to the 3D folding of vasopressin.

Surrogate vasopressin marker

The size and half-life of copeptin permit an easier immunological testing, compared to vasopressin, and hence copeptin is proposed as a reliable AVP surrogate. The clinical interest in copeptin testing is closely linked to the pathophysiological pathways in which vasopressin is involved: polydipsia-polyuria syndrome, hyponatremia,

syndrome of inappropriate antidiuretic hormone secretion Syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of Vasopressin, antidiuretic hormone (ADH) either from ...

(SIADH) as well as heart failure and acute coronary syndrome.

In blood

The

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

of copeptin in the

blood circulation In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart an ...

ranges from 1 to 12 p mol/L in healthy individuals. The levels of copeptin are slightly higher in men than in women and are not influenced by age. In response to serum osmolality fluctuations, the kinetics of copeptin are comparable to those of vasopressin. For example, patients with an electrolyte disorders such as diabetes insipidus with very low vasopressin concentrations also show very low copeptin concentrations in

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

. On the other hand, patients with

show high concentrations of both vasopressin and copeptin.

Acute myocardial infarction

Several studies have shown that copeptin is released very early during the onset of an acute myocardial infarction (AMI), raising the question of its potential value in the

diagnosis Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...

of AMI and particularly in ruling-out AMI. Indeed, copeptin is released much earlier than

troponin Troponin, or the troponin complex, is a complex of three regulatory proteins (troponin C, troponin I, and troponin T) that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-spe ...

, given that copeptin is actively released from the

, while

occurs in the bloodstream as a breakdown product from dying cardiomyocytes, making the interpretation of their complementary kinetics a useful tool to rule-out AMI. It has been shown that the combination of a negative result of troponin together with a negative result of copeptin can rule out AMI at

emergency department An emergency department (ED), also known as an accident and emergency department (A&E), emergency room (ER), emergency ward (EW) or casualty department, is a medical treatment facility specializing in emergency medicine, the Acute (medicine), ...

presentation with a negative predictive value ranging from 95% to 100%. These results have been confirmed in a randomised controlled trial.

Cardiogenic shock

High concentrations of vasopressin during

cardiogenic shock Cardiogenic shock is a medical emergency resulting from inadequate blood flow to the body's organs due to the dysfunction of the heart. Signs of inadequate blood flow include low urine production (<30 mL/hour), cool arms and legs, and decreased ...

have been widely described. It has been shown that the kinetics of copeptin are similar to vasopressin in that context.

Heart failure

The prognostic value of vasopressin for prediction of outcome in patients with

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

has been known since the 1990s. Patients presenting with high levels of vasopressin have a worsened outcome. Recently, a similar interest has been demonstrated for copeptin in heart failure.

References

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