All Topics  
Lysyl oxidase

 

 
   Email Print
   Bookmark   Link
 

 

Lysyl oxidase
 
 
  Topics Lysyl oxidase Topic Home

Lysyl oxidase also known as protein-lysine 6-oxidase is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 which in humans is encoded by the LOX gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
. Its inhibition can cause lathyrism
Lathyrism

Lathyrism or Neurolathyrism is a neurological disease of humans and domestic animals, caused by eating certain legumes of the genus Lathyrus....
, but at the same time, its upregulation by tumor
Tumor

A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be Benign neoplasm, Carcinoma in situ or malignant, whereas cancer is by definition malignant....
 cells may promote metastasis
Metastasis

Metastasis , or Metastatic disease, sometimes abbreviated mets, is the spread of a disease from one Organ or part to another non-adjacent organ or part....
 of the existing tumor, causing it to become malignant and cancerous
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
.

Function
Lysyl oxidase is an extracellular copper enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 that catalyzes formation of aldehydes from lysine
Lysine

Lysine is an a-amino acid with the chemical formula HO2CCH4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it....
 residues in collagen
Collagen

Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content....
 and elastin
Elastin

Elastin is a protein in connective tissue that is Elasticity and allows many tissues in the body to resume their shape after stretching or contracting....
 precursors.






Discussion
Ask a question about 'Lysyl oxidase'
Start a new discussion about 'Lysyl oxidase'
Answer questions from other users
Full Discussion Forum



Encyclopedia


Lysyl oxidase also known as protein-lysine 6-oxidase is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 which in humans is encoded by the LOX gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
. Its inhibition can cause lathyrism
Lathyrism

Lathyrism or Neurolathyrism is a neurological disease of humans and domestic animals, caused by eating certain legumes of the genus Lathyrus....
, but at the same time, its upregulation by tumor
Tumor

A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be Benign neoplasm, Carcinoma in situ or malignant, whereas cancer is by definition malignant....
 cells may promote metastasis
Metastasis

Metastasis , or Metastatic disease, sometimes abbreviated mets, is the spread of a disease from one Organ or part to another non-adjacent organ or part....
 of the existing tumor, causing it to become malignant and cancerous
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
.

Function


Lysyl oxidase is an extracellular copper enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 that catalyzes formation of aldehydes from lysine
Lysine

Lysine is an a-amino acid with the chemical formula HO2CCH4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it....
 residues in collagen
Collagen

Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content....
 and elastin
Elastin

Elastin is a protein in connective tissue that is Elasticity and allows many tissues in the body to resume their shape after stretching or contracting....
 precursors. These aldehydes are highly reactive, and undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This results in cross-linking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin.

Complex cross-links are formed in collagen (pyridinolines derived from three lysine residues) and in elastin (desmosine
Desmosine

A desmosine cross-link is formed from three allysyl side chains plus one unaltered lysyl side chain from the same or neighbouring polypeptides....
s derived from four lysine residues) that differ in structure.

The importance of lysyl oxidase-derived cross-linking was established from animal studies in which lysyl oxidase was inhibited either by nutritional copper-deficiency or by supplementation of diets with ß-aminopropionitrile (BAPN), an inhibitor of lysyl oxidase. This resulted in lathyrism
Lathyrism

Lathyrism or Neurolathyrism is a neurological disease of humans and domestic animals, caused by eating certain legumes of the genus Lathyrus....
, characterized by poor bone formation and strength, hyperextensible skin, weak ligaments, and increased occurrence of aortic aneurysms. These abnormalities correlated well with decreased cross-linking of collagen and elastin.

Clinical significance


LOX expression is regulated by hypoxia-inducible factors (HIFs) and hence LOX expression is often upregulated in hypoxic
Hypoxia (medical)

Hypoxia is a Pathology condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise....
 breast and head and neck tumors. Patients with high LOX-expressing tumors have poor overall survival. Furthermore, inhibition of LOX has been demonstrated to eliminate metastases in mice. Secreted LOX is responsible for the invasive properties of hypoxic cancer cells through focal adhesion kinase
PTK2

PTK2 protein tyrosine kinase 2 , also known as Focal Adhesion Kinase , is a protein which in humans is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes....
 activity and cell-to-matrix adhesion. LOX may be required to create a niche permissive for metastatic growth and thus may be required for hypoxia-induced metastasis.

In a rodent model of breast cancer, a small-molecule or antibody inhibitors of LOX abolished metastasis. LOX secreted by hypoxic breast tumor cells crosslinks collagen
Collagen

Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content....
 in the basement membrane
Basement membrane

The basement membrane is a sheet of cells and fibers that covers two other kinds of cells -- the epithelium, which lines the cavities and surfaces of organs, and the endothelium, which lines the interior surface of blood vessels....
 and is essential for CD11b+
Integrin alpha M

Integrin alpha M is one protein subunit that forms the heterodimeric integrin alpha-M beta-2 molecule, also known as macrophage-1 antigen or complement receptor 3 ....
 myeloid cell recruitment. CD11b+ cells in turn adhere to crosslinked collagen and produce matrix metalloproteinase-2
MMP2

Matrix metallopeptidase 2 , also known as MMP2, is a human gene. section_title =| summary_text = Proteins of the matrix metalloproteinase family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes,...
, which cleaves collagen, enhancing the invasion of metastasizing tumor cells. Conversely LOX inhibition prevents CD11b+ cell recruitment and metastatic growth.

Hence inhibitors of the LOX enzyme may be useful in preventing tumor progression and metastasis as well as treating other fibrotic disease involving remodeling of the extracellular matrix
Extracellular matrix

In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal Cell in addition to performing various other important functions....
 including neurodegenerative and cardiovascular diseases.

See also

  • oxidase
    Oxidase

    An oxidase is any enzyme that catalyst an redox reaction involving molecular oxygen as the electron acceptor. In these reactions, oxygen is reduced to water or hydrogen peroxide ....


Further reading



External links