Thyroxine isolation

When thyroxine (57) was irradiated through a Coming filter which cut out wavelengths below 340 nm, photolysis was slower and it was possible to isolate reasonable yields of 3,3, 5-triiodothyronine. This was resistant to further loss of iodine, but 3,5-diiodothyronine slowly accumulated on prolonged exposure... 

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

Thyroxine and triiodothyronine have many effects, a major one in mammals and birds being stimulation of energy metabolism in tissues. It has long been recognized that a deficiency of thyroid hormone is reflected in an overall lower basal metabolic rate (Chapter 6). Maley and Lardy observed that thyroxine uncouples oxidative phosphorylation (Chapter 18) in isolated mitochondria.117 When mitochondria from animals receiving extra thyroxine were compared with those from control animals, an increased rate of electron transport was observed. However, there was little or no change in the P / O ratio. Thus, the hormone apparently increased the rate of electron transport... 

The second alternative function of PDI again comes from sequence analysis. This time a clone isolated as a lodothyronine 5 -monodeiodinase (5 -MD, thyroxine deiodinase) from rat codes for a protein that is identical to PDI in all but two residues (Boado et ai, 1988). The clone was isolated by screening a library with polyclonal antibodies raised against rat liver microsomal proteins. Clones coding for 5 -MD were selected by... 

In 1914 he isolated thyroxine, the active principle of the thyroid gland. Kendall isolated and identified a series of compounds from the adrenal gland cortex and, with Merck Co., Inc., prepared cortisone by partial synthesis. He also investigated the effects of cor-... 

C. Pantos, I. Mourouzis, S. Tzeis, P. Moraitis, V. Malliopoulou, D.D. Cokkinos, H. Carageorgiou, D. Varonos, D.V. Cokkinos, Dobutamine administration exacerbates postischemic myocardial dysfunction in isolated rat hearts An effect reversed by thyroxine pre-treatment, Eur J Pharmacol 460,155-161 (2003). 

The role of thyroid hormone in the response of the heart to ischemia and reperfusion has not been extensively investigated due to the fact that thyroid hormone accelerates heart rhythm and increases oxygen consumption, effects which could be detrimental in the setting of ischemia and reperfusion. However, accumulating experimental evidence shows that either acute or chronic pretreatment with thyroid hormone can lead to cardioprotection. In an isolated working rat heart model, cardiac work and cardiac efficiency were increased after no-flow global ischemia and reperfusion in hearts acutely pretreated with Tr74 Furthermore, thyroxine pretreatment for two weeks resulted in increased recovery of function in isolated rat hearts subjected to zero-flow... 

Figure 3. Lcll ventricular pressure recordings obtained from isolated rat hearts subjected to zero-flow global ischemia and reperfusion. Ischemic contracture is exacerbated in thyroxine treated hearts (13) and is suppressed in the hypothyroid hearts (C) as compared to normal hearts (A). Recovery of left ventricular developed pressure is increased in both hypothyroid and hyperthyroid as compared to normal hearts. LVDP is defined as the difference between systolic and diastolic left ventricular pressure (data from our laboratory).

The science of endocrinology was developing rapidly at this time. Outstanding was the isolation of insulin for treatment of diabetes by Banting in the early 1920s. Continuing research in this field led to the development of many hormones for treatment of a wide variety of disorders, especially the adrenal cortical steroid hormone (ACTH), cortisone, and thyroxine. 

Riley, W.W. and J.G. Eales. Characterization of L-thyroxine transport into hepatocytes isolated from juvenile rainbow trout (Oncorhynchus mykiss). Gen. Comp. Endocrinol. 90 31-42, 1993. 

Thyroxine is one of the few hormones for which unequivocal effects on isolated biochemical systems can be observed in particular, it has been shown that thyroxine at high concentrations has a direct effect on mitochondrial oxidation. Tissues from animals which have been injected with thyroid extracts or purified thyroxine show a raised oxygen consumption, particularly in liver and muscle. Similarly the addition of thyroxine to tissue slices of the same organs results in increased oxidation. Thyroxine seems to be especially trapped by the mitochondria, where it stimulates the... 

Synthroid is a synthetic form of the thyroid hormone thyroxine (T-4). Thyroxine was the first thyroid hormone isolated by scientists, who at first mistakenly thought it was the primary thyroid hormone. Later we have come to find however that T-3 is the hormone which displays the most activity. Thyroxine is actually looked at as a relatively inactive thyroid product in its initial state, and exerts most of its action by converting to T-3. 80% of blood T-3 actually comes from... 

B14a. Becker, D. V., and Prudden, J. F., The metabolism of I-labelled thyroxine, tri-iodothyronine and di-iodotyrosine by an isolated perfused rabbit liver. Endocrinology 64, 136-148 (1959). 

---