Sum activity of peripheral deiodinases

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Reference excerpt

The sum activity of peripheral deiodinases (GD, also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as SPINA-GD) is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assumed to reflect the activity of deiodinases outside the central nervous system and other isolated compartments. GD is therefore expected to reflect predominantly the activity of type I deiodinase. GD is both a theoretical concept that is used in physiological theories of thyroid function and (as a calculated parameter) a biomarker for advanced diagnosis of thyroid disorders.

How to determine GD GD can be determined experimentally by exposing a cell culture system to saturating concentrations of T4 and measuring the T3 production. Whole body deiodination activity can be assessed by measuring production of radioactive iodine after loading the organism with marked thyroxine. However, both approaches are faced with draw-backs. Measuring deiodination in cell culture delivers little, if any, information on total deiodination activity. Using marked thyroxine exposes the body to thyrotoxicosis and radioactivity. Additionally, it is not possible to differentiate step-up reactions resulting in T3 production from the step-down reaction catalyzed by type 3 deiodination, which mediates production of reverse T3. Distinguishing the contribution of distinct deiodinases is possible, however, by sequential approaches using deiodinase-specific blocking agents, but this approach is cumbersome and time-consuming. In vivo, it may therefore be beneficial to estimate GD from equilibrium levels of T4 and T3. It is obtained with

G ^ D = β 31 ( K M 1 + [ F T 4 ] ) ( 1 + K 30 [ T B G ] ) [ F T 3 ] α 31 [ F T 4 ] {\displaystyle {\hat {G}}_{D}={{\beta _{31}(K_{M1}+[FT_{4}])(1+K_{30}[TBG])[FT_{3}]} \over {\alpha _{31}[FT_{4}]}}}

or

G ^ D = β 31 ( K M 1 + [ F T 4 ] ) [ T T 3 ] α 31 [ F T 4 ] {\displaystyle {\hat {G}}_{D}={{\beta _{31}(K_{M1}+[FT_{4}])[TT_{3}]} \over {\alpha _{31}[FT_{4}]}}}

[FT4]: Serum free T4 concentration (in pmol/L) [FT3]: Serum free T3 concentration (in pmol/L) [TT3]: Serum total T3 concentration (in nmol/L)

α 31 {\displaystyle \alpha _{31}} : Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 L−1)

β 31 {\displaystyle \beta _{31}} : Clearance exponent for T3 (8e-6 sec−1) (i. e., reaction rate constant for degradation) KM1: Binding constant of type-1-deiodinase (5e-7 mol/L) K30: Binding constant T3-TBG (2e9 L/mol) The method is based on mathematical models of thyroid homeostasis. Calculating deiodinase activity with one of these equations is an inverse problem. Therefore, certain conditions (e.g. stationarity) have to be fulfilled to deliver a reliable result. The product of SPINA-GD times the urinary iodine excretion can be used to assess iodine-independent factors affecting deiodinase activity, e.g. selenium deficiency.

Reference range

The equations and their parameters are calibrated for adult humans with a body mass of 70 kg and a plasma volume of ca. 2.5 L.

Clinical significance

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Worked examples

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Example 2 — changing one variable

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Example 3 — an exam-style question

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Applications of Sum activity of peripheral deiodinases

In research: Sum activity of peripheral deiodinases appears in mathematics research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Sum activity of peripheral deiodinases in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Sum activity of peripheral deiodinases is common in secondary-school and first-year university syllabi. It links to neighbouring topics Blood tests, Clinical chemistry, Endocrine procedures, so understanding it makes those chapters shorter.
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Frequently asked questions

What is Sum activity of peripheral deiodinases in simple terms?

The sum activity of peripheral deiodinases (GD, also referred to as deiodination capacity, total deiodinase activity or, if calculated from levels of thyroid hormones, as SPINA-GD) is the maximum amount of triiodothyronine produced per time-unit under conditions of substrate saturation. It is assum…

Why does Sum activity of peripheral deiodinases matter?

Because it connects several mathematics ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Sum activity of peripheral deiodinases?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

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