EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

( An ISO 9001:2015 Certified International Journal )

An International Peer Reviewed Journal for Pharmaceutical, Medical & Biological Sciences

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

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 ISSN 2394-3211

Impact Factor: 6.222

 ICV - 79.57

Abstract

BIOCHEMICAL BASIS OF MITOCHONDRIAL DYSFUNCTION IN HYPOTHYROIDISM

Dr. Sadhna Ajay ?, Dr. Rajesh Pandey and Dr. S. K. Aggarwal

ABSTRACT

Thyroid hormones are required for normal function of most tissues of the body, playing essential roles in growth, development, differentiation and metabolism with major effects on O2 consumption and metabolic rate. Mitochondria by virtue of their biochemical function are natural candidates as the target for the calorigenic effects of thyroid hormone. Thyroid hormone might act at several sites in the mitochondria to regulate cell respiration. Site 1: Activity of ADP/ATP translocase. Site 2: Citric acid cycle intermediates. Site 3: Phosphate transporter. Site 4: F0F1 ATPase and Site 5: Electron transport chain. ANT, which exerts major control over the rate of oxidative phosphorylation maybe a direct target of T3 action on the mitochondria. Biochemical basis of the mitochondrial dysfunction related with low level of ANT in hypothyroidism is due to low level of cardiolipin. The activity of the crab cycle is not specifically affected by the hypothyroidism. There is a decrease in phosphate transporter activity in hypothyroidism and it can be due to an effect of thyroid hormones on lipid microenvironment of the phosphate carrier. The hepatic mitochondrial lipid composition is altered significantly in hypothyroidism. It is probably a nuclear effect of thyroid hormone, as it is on phosphate transport in kidney and liver. The electron transport chain complexes and F0F1 ATPase activity are decreased in many tissues in thyroid deficient conditions. Hypothyroidism affects the expression of mitochondrial proteins from respiratory chain. In state 3 respiration, the major effect of decrease in thyroid hormones is via changes in the reactions involved in the phosphorylation of ADP and the export of ATP, probably at the adenine nucleotide carrier. In state 4 respiration, the rate is controlled very largely by the proton leak across the mitochondrial inner membrane. Leak is depressed in hypothyroid mitochondria due to alterations in membrane fatty acid composition primarily in n-3 content. Fatty acids are not only inducers of uncoupling but they have also a regulatory function in this process. Thyroid hormone has an impact on membrane fluidity and lipid composition. Hypothyroidism causes decreased membrane rigidity and greater extent of mitochondrial membrane lipid damage. Chronic state of hypothyroidism is characterized with impairments in the redox potential leading to free radical chain reactions and to metabolic suppression of antioxidant capacity. Accumulation of ROS and loss of membrane integrity are two primary factors that potentially trigger apoptosis.

Keywords: ANT(Adenine nucleotide translocase), ROS(reactive oxgen species), Mitochondria, Hyporhyroidism.


[Full Text Article]

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Google Scholar Indian Science Publications InfoBase Index (In Process) SOCOLAR, China Research Bible, Fuchu, Tokyo. JAPAN International Society for Research activity (ISRA) Scientific Indexing Services (SIS) Polish Scholarly Bibliography Global Impact Factor (GIF) (Under Process) Universal Impact Factor International Scientific Indexing (ISI), UAE Index Copernicus CAS (A Division of American Chemical Society) USA (Under Process) Directory of Open Access Journal (DOAJ, Sweden, in process) UDLedge Science Citation Index CiteFactor Directory Of Research Journal Indexing (DRJI) Indian citation Index (ICI) Journal Index (JI, Under Process) Directory of abstract indexing for Journals (DAIJ) Open Access Journals (Under Process) Impact Factor Services For International Journals (IFSIJ) Cosmos Impact Factor Jour Informatics (Under Process) Eurasian Scientific Journal Index (ESJI) International Innovative Journal Impact Factor (IIJIF) Science Library Index, Dubai, United Arab Emirates Pubmed Database [NLM ID: 101669306] (Under Process) IP Indexing (IP Value 2.40) Web of Science Group (Under Process) Directory of Research Journals Indexing Scholar Article Journal Index (SAJI) International Scientific Indexing ( ISI )