Thyroxine 5-deiodinase also known as type III iodothyronine deiodinase (EC number 1.21.99.3) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''DIO3'' gene. This enzyme catalyses the following

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

: 3,3',5'-triiodo-L-thyronine +

iodide An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered as a component of iodized salt, which many governments mandate. Worldwide, iodine defic ...

+ A + H⁺

\rightleftharpoons

L-

thyroxine File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

+ AH₂ The protein encoded by this intronless gene belongs to the

iodothyronine deiodinase Iodothyronine deiodinases ( and ) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T4), the precursor of 3,5,3'-triiodothyronine (T3) is transformed into T3 by deiodinase activity ...

family. It catalyzes the inactivation of

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

by inner ring deiodination of the prohormone

(T₄) and the bioactive hormone 3,3',5-triiodothyronine (T₃) to inactive metabolites, 3,3',5'-triiodothyronine (RT₃) and

3,3'-diiodothyronine 3,3'-Diiodothyronine, also known as 3,3'-T2, is a metabolite of thyroid hormone. It is formed from the breakdown of triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the ...

(T₂), respectively. This enzyme is highly expressed in the pregnant uterus, placenta, fetal and neonatal tissues, suggesting that it plays an essential role in the regulation of thyroid hormone inactivation during embryological development.

Discovery

The gene was mapped to chromosome 14q32 using

fluorescence in situ hybridization Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed b ...

(FISH) in 1998.

Structure

This protein contains a

selenocysteine Selenocysteine (symbol Sec or U, in older publications also as Se-Cys) is the 21st proteinogenic amino acid. Selenoproteins contain selenocysteine residues. Selenocysteine is an analogue of the more common cysteine with selenium in place of the s ...

(Sec) residue, which is essential for efficient enzyme activity. The selenocysteine is encoded by the UGA

codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

, which normally signals translation termination. The 3' UTR of Sec-containing genes have a common stem-loop structure, the sec insertion sequence (SECIS), which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal.

Function

The ''DIO3'' gene codes for type 3

(D3), an enzyme that inactivates

thyroid hormones File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

and is highly expressed throughout

fetal development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

, peaking early and decreasing towards the end of gestation. Part of the

DLK1 Protein delta homolog 1, delta like non-canonical Notch ligand 1, fetal antigen 1 or preadipocyte factor 1 is a protein that in humans is encoded by the ''DLK1'' gene. It is expressed as a transmembrane protein, but a soluble form cleaved off by ...

-Dio3 imprinting control region, this gene is one involved in the

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

process that causes a subset of genes to be regulated based on their parental origin . Such imprinted genes are required for the formation of the

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...

as well as the development of cellular lineages such as those derived from the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

and

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...

. D3 is found in the pregnant uterus, placenta, and mammalian fetal tissues where it is thought to be involved in the transfer of thyroid hormone between the mother and fetus. Expression of D3 contributes to the development of the brain, skin, liver, bone, ovary, testis, intestine, and

brown adipose tissue Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). Brown adipose tissue is found in almost all mammals. Classification of brown fat refers to two distinct cell populations with si ...

. Introductory observations of D3-deficient mice indicate growth retardation and even some

neonatal death Perinatal mortality (PNM) refers to the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. Variations in the precise definition of the perinatal mortality exist, specifically concerning the issue of inclusion o ...

. Due to its ability to activate or inactivate thyroid hormone, Dio3 coding of D3 could be a target for therapeutic intervention in insulin-related illness such as

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

. In addition, an abnormal amount of Dio3 related to insufficient thyroid hormone levels could be responsible for the disruption of brain development in conjunction with alcohol exposure. Many factors modify genetic imprinting of Dio3, making it a potential aid in understanding prenatal insults and their production of spectrum disorders.

References

External links

* {{NLM content EC 1.21.99 Genes on human chromosome 14 Developmental genes and proteins

Discovery

Structure

Function

References

Further reading

External links