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Low-molecular-weight chromium-binding substance (LMWCr; also known as chromodulin) is an
oligopeptide An oligopeptide ('' oligo-'', "a few"), is a peptide consisting of two to twenty amino acids, including dipeptides, tripeptides, tetrapeptides, and other polypeptides. Some of the major classes of naturally occurring oligopeptides include aerugi ...
that seems to transport
chromium Chromium is a chemical element; it has Symbol (chemistry), symbol Cr and atomic number 24. It is the first element in Group 6 element, group 6. It is a steely-grey, Luster (mineralogy), lustrous, hard, and brittle transition metal. Chromium ...
in the body. It consists of four amino acid residues;
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 ...
,
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
,
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
, and
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
, bonded with four (Cr3+) centers. It interacts with the insulin receptor, by prolonging
kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
activity through stimulating the
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
pathway, thus leading to improved glucose absorption. and has been confused with glucose tolerance factor. The exact mechanisms underlying this process are currently unknown. Evidence for the existence of this protein comes from the fact that the removal of 51Cr in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
exceeds the rate of 51Cr formation in the
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
. This indicates that the transport of Cr3+ must involve an intermediate (i.e. chromodulin) and that Cr3+ is moved from the blood to tissues in response to increased levels of insulin. Subsequent protein isolations in rats, dogs, mice and cows have shown the presence of a similar substance, suggesting that it is found extensively in
mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
. This oligopeptide is small, having a
molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
of around 1 500 g/mol and the predominant
amino acids 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 Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
present are
aspartic acid 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 protei ...
,
glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) 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 ...
,
glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
, and
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
. Despite recent efforts to characterize the exact structure of chromodulin, it is still relatively unknown.


Nature of binding

From spectroscopic data, it has been shown that Cr3+ binds tightly to chromodulin ( Kf = 1021 M−4), and that the binding is highly
cooperative A cooperative (also known as co-operative, coöperative, co-op, or coop) is "an autonomy, autonomous association of persons united voluntarily to meet their common economic, social and cultural needs and aspirations through a jointly owned a ...
( Hill Coefficient = 3.47). It has been shown that holochromodulin binds 4 equivalents of Cr3+. Evidence for this comes from
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
studies which showed that apochromodulin exerts its maximal activity on insulin receptors when titrated with 4 equivalents of Cr3+. Chromodulin is highly specific for Cr3+ as no other metals are able to stimulate
tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...
activity. It is believed to stimulate the
phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
of the 3
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
residues of the β subunits of the insulin receptor. From electronic studies, the crystal field stabilization energy was determined to be 1.74 x 103 while the Racah parameter B was 847 cm−1. This indicates that chromium binds to chromodulin in the trivalent form. In addition,
magnetic susceptibility In electromagnetism, the magnetic susceptibility (; denoted , chi) is a measure of how much a material will become magnetized in an applied magnetic field. It is the ratio of magnetization (magnetic moment per unit volume) to the applied magnet ...
studies have shown that chromium does not
coordinate In geometry, a coordinate system is a system that uses one or more numbers, or coordinates, to uniquely determine and standardize the position of the points or other geometric elements on a manifold such as Euclidean space. The coordinates are ...
to any
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
amine groups but rather to
carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an anion, an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,... ...
s (although the exact the amino acids involved are still unknown). These magnetic susceptibility studies are consistent with the presence of a mononuclear Cr3+ center and an unsymmetric trinuclear Cr3+ assembly with bridging oxo ligands. In chromodulin isolated from bovine liver, x-ray absorption spectroscopy studies have shown that the chromium (III) atoms are surrounded by 6 oxygen atoms with an average Cr—O distance of 1.98 Å, while the distance between 2 chromium (III) atoms is 2.79 Å. These results are indicative of a multinuclear assembly. No sulfur ligands coordinate to chromium and instead, it has been proposed that a disulfide linkage between 2
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
residues occurs owing to a characteristic peak at 260 nm.


References

{{reflist Peptides