Biochemistry of Hyperhypothyroidism
The hormones from the thyroid gland directly affect the mitochondria.
The action of these hormones on the mitochondria makes them control the changing of energy acquired from oxidation into a form that can be used by the cell and cell processes. Additionally, due to the direct action of the thyroid hormones on mitochondria, they are able to regulate the rate at which protein molecules are formed. This means that they regulate the quantity of the oxidative apparatus forum in the cell. The rationale used to discuss the effects of deficiency or overabundance is based upon research of the mode of action through which these hormones act. The deficiency of the thyroid hormones is referred to as hypothyroidism while the excess supply of thyroid hormones is referred to as hyperthyroidism.
This paper will discuss the biochemistry of hyperthyroidism as well and that of hypothyroidism (Gheri,2004). Hypothyroidism is exhibited by very minimal rate of fuel consumption. Due to this low rate of fuel consumption, hypothyroidism results in a slow release of energy that can be utilized by the body. On the other hand, hyperthyroidism is characterized by rapid fuel uptake which ultimately leads to a high output of energy that can be utilized by the body. However, as the efficiency of releasing energy decreases, the amount of energy that can be utilized decreases.
A Deficiency or excess of the quantity of thyroid hormones, results in severe chemical and clinical indications. These indications involve several metabolic systems as well and organs. The changes in the concentration of the thyroid hormones in vivo, results in a change,in the consumption of oxygen, growth and development and regulation of temperature. Additionally, it also leads to a change in the body’s response to other hormones, change in the metabolism of fats and carbohydrates, proteins, vitamins, nucleic acids and inorganic cations and anions. Triiodothyronine and thyroxin are quite simple in their structure and have a small size.
The size of molecules limits the number of reactive groups. This suggests that the different reactions that they take part are as a result of the few primary interactions or that the hormones undergo a transformation in the body to become analogues each with a specific and varied effect on the physiology (Yu, et al 2006). How Thyroid Hormones Act and their Effects After Magnus Levy proved that the rate at which mammals consumed oxygen was controlled by the thyroid gland, attention has shifted on proving that the hormone’s target are the oxidative processes of the body. Kendall was able to describe the structure of the hormone thyroxin and proposed that the hormone could be a coenzyme or sub component of oxidative enzyme. The oxidative enzyme passes through a redox cycle that revolves around the semiquinone and phenol forms.
Despite this proposition, there is no concrete evidence to back Kendall’s hypothesis between 1940 and 1950, it was discovered that over 90% of oxygen in a cell was used up in mitochondrial processes. Numerous experiments were carried out in vitro and in vivo on thyroid hormones in an attempt to determine the effect that they had on the mitochondria of a cell. It is prudent for one to differentiate between the effects and the actions of the thyroid hormones. The ‘actions’ of the hormones refer to the structural or functional changes which are dependent on the hormone’s presence at a particular location for interaction with specific molecules within the apparatus of the cell. Due to the effectiveness of hormones in very small quantities, it is assumed that these fundamental interactions within the molecules can be easily reversed so that the hormones do not become depleted. On the hand, ‘effects,’ refers to changes that are compositional, functional or structural and secondary.
Consequently, they are independent of the presence of the hormone and cannot be reversed when the hormone is extracted after it has acted (Gaw 2008). This differentiation however does not make a clear judgment of their importance in the cell. Thyroid hormones are especially important for the specification of secondary effects from the primary effects. This is because the iodine moieties that they contain can be utilized as a tracer in carrying out quantitative analysis in an experiment. The thyroid hormone can be shown experimentally to affect the mitochondria in a similar manner to 2,4-dinitrophenol. This agent is known to enhance respiration within the mitochondria.
However, the energy that was derived from the process was not converted into the normal form that can be utilized, but was rather converted into heat and dissipated. It is this observed catabolic, energy wasting and toxic effect that acted as the thyrotoxicosis rationale. However, it did not form the basis for the energy conserving, anabolic and non-toxic ffects that were observed by minimal doses of thyroid hormones that were exerted in hypothyroid or the subjects who were euthyroid (Ramakrishna 2004). Changes in Metabolism There are several fundamental features of experimental and clinical hyperthyroidism and hypothyroidism that are considered to be the manifestation of variations in how energy is transformed. However, there is more evidence on the relation between the basic changes and the manifestations in hyperthyroidism as compared to that in hypothyroidism.
Metabolism of Proteins Protein synthesis and breakdown is directly controlled by the thyroid hormones. The thyroid status of a subject determines the effect that the administered thyroid hormones will have on them. Protein synthesis is stimulated by low doses of hormone thyroxin while , on the other hand, high dose of the thyroxin hormone suppresses protein synthesis. A dose of L-T3 is known to decrease the rate of protein synthesis in humans who are euthariod. However, the same dose was seen to improve and increase the rate of synthesizing proteins among patients who were myxoedematous.
Humans who are hyperthyroid posses extremely low amounts of parenchymal protein. This is observed in their liver biopsies.These observations were consistent with the results obtained from experiments conducted upon rats that indicated a decreased peptide linkage synthesis. However, there was an increase in the free amino acid concentration,in blood, as well as in the muscle and the liver of rats that were thyrotoxic (Heymann 2008). Metabolism of Lipids Thyroid hormones also regulate the rate at which lipids are synthesized, oxidized and mobilized.
There are several biphasic effects on the synthesis of lipids that have been indicated on the synthesis of lipids. 20 micrograms of the hormone thyroxin resulted in an observable increase, in the rate at which cholesterol was synthesized from acetate by the fractions of rat livers that were cell free. 30-50 micrograms resulted in an observable decrease,in cholesterol synthesis. Humans and Rats who were treated with thyroxin exhibited a rapid rate of synthesizing cholesterol than is normal. Additionally, the rate at which fatty acids and cholesterol are synthesized in the tissues of rats that were treated with hormones was determined.
On the other hand, the rate of synthesis of cholesterol was observed to decline in the livers of preparations that were cell free as well as in homogenates obtained from rats that were thyrotoxic. The neutral fat content and the cholesterol content in the livers of rats treated with thyroxin and the human body’s fat content were observed to drop below the base value for hyperthyroidism. The process of thyroidectomy lowered the rate at which cholesterol was synthesized. Thyroid hormones raised the rate at which cholesterol was synthesized in subjects who were myxoedematous. However, the regulation of the process of synthesizing lipids by thyroid hormones. The observed increase and defects in the synthesis of lipids can be attributed to variations in the availability of Adenosine Tri-phosphate (ATP) at different stages of the process.
This is despite the fact that the mitochondria were not available during the preparation of synthesizing. Therefore, the observed effects due to thyroid hormones have been attributed to changes in the supply of acetyl-Co A. Thyroid hormones are also responsible for the regulation of concentration fatty acid in body tissues. This is done by mobilizing the fatty acids deposited in the adipose tissue (Gheri, et al 2004). Metabolism of Carbohydrate Thyroid hormones regulate the rate of glycogen synthesis and the rate of oxidation of hexose sugar. Additionally, thyroxin has a biphasic effect on the synthesis of glycogen.
Minimal thyroxin doses raise the rate at which glucose is produced in the diaphragms of rats. This happens either in vitro or in vivo. However, a larger dose of the hormone causes a reverse in this effect. This process depends only on the supply of ATP available. Evidence shows that glucose synthesis declines as a result of thyrotoxicosis.
Hyperthyroid humans show a decreased rate of synthesizing glycogen. The amount of glycogenin the muscles and the liver are extremely diminished in subjects who are hyperthyroid. This is especially evident for the forms of glycogen that are considered metabolically active. However, this low glycogen level cannot be entirely pegged on the hormone as it could also be as a result of rapid breakdown. The decrease in ATP levels in the muscles and the liver appears consistent when thyroid hormone is administered.
Epinephrine has a hyperglycemic effect when mediated via an increasing cyclic-3′, 5′-AMP and the corresponding phophorylase. This depends on the state of the thyroid horrmone. When the thyroid hormone is administered, a significant biphasic effect is produced. A minimal T4 dose is observed to raise the hyperglycemia effect of the epinephrine that is administered. The quantity of glycogen in the liver is also observed to interfere with the hyperglycemic variation in response to the administered epinephrine.
If thyrotoxicosis is prolonged, the glycogen in the liver of the organism is depleted, and no hyperglycemia will accompany the administration of epinephrine. In the case of hypothyroidism, administration of epinephrine exhibited lower than the expected responses. Thyroid hormones influence the oxidation and phosphorylation of hexose sugar, by altering how the other hormones act. Hexose oxidation is sped up by administration of thyroid hormones either via an increase in the rate of glycolysis or through an equal raise in the glycolytic or the phopshogluconate pathways (Ramakrishna, 2004). Temperature Regulation The thyroid hormones play a crucial role in the regulation of body temperature. Up to 60% of the total amount of energy released from oxidations in the mitochondria is transformed into a form that can be utilized chemically by the body.
The remaining 40% is released as heat and is responsible for the maintenance of homeotherm’s body temperature. In hyperthyroidism, there are two factors that lead to the generation of heat. These factors are; an increased rate of oxidation and decreased energy conversion efficiency. Normally, the surplus amounts of heat energy are dispelled through means that are physiologically compensating such as sweating, flushing and an increase in the circulation. Most of the clinical indications of an individual suffering from hyperthyroidism are depicted by such compensations.
A thyrotoxic crisis is a situation in which the body fails to compensate due to an increase raise in the heat produced. This happens due to a decrease in the efficiency of the mitochondria. The body temperatures plummet to 1070 F or higher. Additionally, the patient may lose muscle tone and experience liver damage. Refrigeration of the body may serve to dissipate most of the heat and salvage the situation.
However, therapeutic mechanisms to initiate the secretion of adrenocortical hormones that would cause an antagonistic effect with the adrenomedullary hormones can be used successfully. Through experimental induction of hyperthermia, a condition exhibited during hyperthermia, during thyroid crisis, clearly depict the action of thyroid hormone physiologically. Large doses of thyroid hormone administered to animals results in a dramatic loss in the animal’s weight and eventually dies apathetically and not due to hyperthermic crisis. However, the administration of controlled amounts of thyroid hormone can result in a fatal state of hyperthermia, especially if accompanied by an agent that provides oxidative metabolism such as dinitro-o-cresol and methylen blue. In hypothyroidism, the production of heat is reduced by a declined rated of the oxidation of the mitochondria. Psychological compensations also serve to preserve the heat generated by the body.
The temperature of the body may fall below the normal body temperature. If infected by illnesses that cause fever and temperature raise, the hypothyroid’s temperature does not rise. If not treated in time, a severe case of myxoedema coma may result (Gheri 2004). Conclusion There are other clinical features that are associated with hypothyroidism and hyperthyroidism which are not directly manifested as a change in the energy transfers between the cells. These features can be classified into two. First, there are features that come about not due to the varying amounts of thyroid hormones, but as a result of phenomena that are related to a primary malfunction in the production of thyroid hormone.
Secondly, are the clinical features that seem to arise from varying amounts of the thyroid hormone tissue, but cannot be determined to be assumed to be due to cellular preparations since there is not enough information yet on them. Patients suffering from hyperthyroidism may exhibit hyper irritability. This effect on the nervous system is due to the role played by ATP in the process of nerve conduction as well as in the resynthesis of acetylcholine. This happens at the myoneural junction, and it involves Calcium, magnesium and Potassium ions. Thyroid hormones regulate growth and development as well as the chemical and structural changes that occur in anuran metamorphosis. All these processes rely upon the availability of energy.
Recent findings suggest thyroid hormones regulate the energy of the mitochondrial metabolism directly. Therefore, they regulate the synthesis of proteins and,therefore, offer the promise of a new and fundamental source of information on the medical and biological problems being faced currently.
