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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

-long

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

derived from the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein i ...

of pre-pro-hormone of arginine

vasopressin Human 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 then trave ...

, and copeptin. Arginine vasopressin (AVP), also known as the

antidiuretic hormone Human 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 then travel ...

(ADH), is encoded by the

AVP gene Arginine Vasopressin (AVP) Gene is a gene whose product is proteolytically cleaved to produce vasopressin (also known as antidiuretic hormone (ADH)), neurophysin II, and a glycoprotein called copeptin. AVP and other AVP-like peptides are found ...

and is involved in multiple cardiovascular and

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

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 (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

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 Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

. It is synthesized mainly in the paraventricular neurons of the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...

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 n ...

. During

axonal transport Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytopla ...

, 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. The posterior pituitary is not glandular as is the anterior pituitary. Instead, it is largely a collection of axonal ...

and released upon

osmotic Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region ...

or non-osmotic ( hemodynamical;

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

-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 (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 The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

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 Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced ...

with very low vasopressin concentrations also show very low copeptin concentrations in

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...

. On the other hand, patients with syndrome of inappropriate antidiuretic hormone secretion 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 A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may t ...

(AMI), raising the question of its potential value in the

diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...

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

troponin image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, ...

, 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 care of pati ...

presentation with a

negative predictive value The positive and negative predictive values (PPV and NPV respectively) are the proportions of positive and negative results in statistics and diagnostic tests that are true positive and true negative results, respectively. The PPV and NPV des ...

ranging from 95% to 100%. These results have been confirmed in a

randomised controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...

Cardiogenic shock

High concentrations of vasopressin during

cardiogenic shock Cardiogenic shock (CS) is a medical emergency resulting from inadequate blood flow due to the dysfunction of the ventricles of the heart.Textbooks of Internal MedicinHarrison's Principles of Internal Medicine 16th Edition, The McGraw-Hill Compan ...

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, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

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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