wada prohibited substances and their biochemical mechanisms 1

WADA prohibited substances and their biochemical mechanisms

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M3 Gene doping

The following, with the potential to enhance sport performance, are prohibited: The transfer of polymers of nucleic acids or

nucleic acid analogues; 轉殖核酸聚合物或核酸類似物

DNA, RNA The use of normal or genetically modified cells. 使用正常或基因改造細胞。

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Anabolic Androgenic Steroids同化性代謝雄性荷爾蒙

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Anabolic Androgenic Steroids同化性代謝雄性荷爾蒙

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Danazol Gestrinone

nandrolone

androgen receptor modulators選擇性 雄激素受體 調節劑

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BMS-564,929

andarine

ostarine

Ex Biochem c25-act transcript 6

25.12 Binding to the Response ElementIs Activated by Ligand-Binding

Binding of ligand to the C-terminal domain increases the affinity of the DNA-binding domain for its specific target site in DNA.

Figure 25.19

S2 peptide hormonesErythropoietin (EPO)

binding to erythropoietin receptor  highly glycosylated 醣化 (40% of total

molecular weight) half-life in blood ~ 5 hr, vary between

endogenous and various recombinant 混合versions

Additional glycosylation or other alterations of EPO via recombinant technology have led to the increase of EPO's stability in blood (thus requiring less frequent injections).

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EPO binds to EpoR on red cell progenitor surface and activates Janus kinase 2 (JAK2) signaling cascade

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Jak-Stat Pathways. Jak-Stat pathways entail the receptor Janus kinase (Jak) and the signal transducer and activator of transcription (Stat).

EPO-related

Methoxy polyethylene glyco-epoetin beta (CERA) 超長效紅血球生成素 Continuous erythropoietin receptor activator 連續性紅血球生成素受體活化劑

 strucutre similar to the previous synthetic EPO drugs, except that it is connected to a chemical called polyethylene glycol (PEG), which makes it last 6-10 X longer in the body.

Non-erythropoietic EPO-Receptor agonists asialo EPO 無唾液酸紅血球生成素

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Hypoxia-inducible factors (HIF)

Transcription factors Functions: angiogenesis 血管增生 ,

development, metabolism HIF Stabilizers 穩定劑 HIF 活化劑 : 氬氣及氙氣

氮氣

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mechanism of HIF

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Peptide hormones

人類絨毛膜性腺激素 (Chorionic Gonadotrophin, CG), or human CG (hCG)

黃體化激素 (Luteinizing Hormone, LH) Both released during pregnancy 懷孕

也可幫助女性懷孕 Manny Ramirez

相關釋放因子 releasing factors

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CG and LH

stimulate testosterone production Failed drug test if urinary testosterone to

epitestosterone (T/E) > 6. hCG ↑endogenous production of testosterone

and epitestosterone without increasing the urinary T/E ratio above normal

hCG also be used following cessation of prolonged anabolic steroid use hasten a return to normal testicular function and

size, when circulating testosterone very low.

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生長激素 growth hormone

生長激素 (GH) 及相關釋放因子， 包括生長素釋素 (GHRH)

其他生長因子 Insulin-like Growth Factor-1 (IGF-l) 似 ( 類 )胰島素生長因子

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生長激素 growth hormone

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S3 beta-2 agonists 致效劑 Beta-2 adrenergic receptor 腎上腺素受體

agonists smooth muscle relaxation 平滑肌舒張 ( 鬆弛 )

dilation of bronchial 支氣管 passages 通道 vasodilation in muscle and liver  Used to treat asthma and other pulmonary

disorders. anabolic effects (↑ muscle mass, ↓body fat

percentage and faster recovery rates)? Most studies showed no ergogenic effect

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S3 beta-2 agonists 致效劑21

S4. Hormone and metabolic modulators 荷爾蒙及代謝調節劑 Aromatase inhibitors 芳香環轉化酶抑制劑

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Testosterone estradiol

androstenedione estrone

S4. Hormone and metabolic modulators 荷爾蒙及代謝調節劑 Selective estrogen receptor modulators

(SERMs) 選擇性雌激素受體調節劑 anti-estrogenic substances 抗雌激素物質

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S4. Hormone and metabolic modulators – myostatin inhibitors

Agents modifying myostatin 肌肉生長抑制素 function myostatin inhibitors 肌肉生長抑制素抑制劑

Disabled myostatin gene increase muscle size

https://www.youtube.com/watch?v=yw4Ci6UrOK0

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Ex Biochem c9-genetics 25Myostatin mutations in animals

Ex Biochem c9-genetics 26

5. Metabolic modulators 代謝調節劑 5.1 腺苷單磷酸活化蛋白激酶調節劑

AMP-activated kinase, AMPK 例如 AICAR

過氧化體增生劑活化受體 delta 致效劑 peroxisome proliferator-activated receptor delta,

PPARdelta 例如 GW 1516

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Ex Biochem c5-CHO metabolism 28AMP-activated protein kinase activation

Effect of AICAR on AMPK

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Pokrywka, 2015

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Pokrywka, 2015

Ex Biochem c25-act transcript 32

PPARs pathway

Ex Biochem c25-act transcript 33GW501516, GW1516PPARdelta agonist

Cause cancer in rats, development stopped by GSK

Effects of GW501516 on PPARdelta

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Pokrywka, 2015

Ex Biochem c25-act transcript 35

Wang YX, PLOSB 2004

WT: wild type

TG: transgenic, 基因轉殖 expression of an activated form of PPARdelta in skeletal muscle

Ex Biochem c25-act transcript 36

Wang YX, PLOSB 2004

GW501516: PPARdelta agonist

Ex Biochem c25-act transcript 37

GW1516 ↑endurance running performance after 5 weeks of training in mice

V: vehicle only, GW: GW1516Narkar, Cell 2008

Ex Biochem c25-act transcript 38

GW1516 in combination with training↑oxidative enzyme expression in mouse quadriceps

V: vehicle only, GW: GW1516, Tr: training, Tr+GW: training + GW1516Narkar, Cell 2008

Ex Biochem c25-act transcript 39Proposed mechanismPGC-1alpha

Narkar, Cell 2008

AICAR5-aminoimidazole-4-carboxamide ribonucleotide

Ex Biochem c25-act transcript 40

粒線體生合成的基因調控機制

Reznick et al, 2006

5. Metabolic modulators 代謝調節劑 5.2 胰島素 5.3 Trimetazidine

可代謝成 amphetamine 安非他命 興奮劑

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Ex Biochem c5-CHO metabolism 42

S5 Diuretics and masking agents利尿劑與干擾劑 血漿擴張劑

甘油及靜脈注射 albumin dextran, hydroxyethylstarch, 甘露醇 mannitol

利尿劑 Acetazolamide 一種利尿劑 , inhibitor of

carbonic anhydrase HCO3- + H+ H2CO3 H2O + CO2 In kidney, allowing the reabsorption of HCO3-,

sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, 

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S6 Stimulants 興奮劑prohibited in-competition 賽內禁用 Amfetamine (amphetamine): 安非他命 Cathine去甲偽麻黄鹼； mephedrone 甲氧麻黄酮 : 可轉換為安非他命

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Cathinemephedrone

amphetamine

S6 Stimulants 興奮劑prohibited in-competition 賽內禁用 Ephedrine 麻黃 Pseudoephedrine  偽麻黃鹼

一種「血管收縮劑」。過敏或感冒 ( 流感 ) 所引起的鼻塞，主要因鼻腔內微血管充血而腫脹的關係。此藥使鼻子內層的血管收縮，使充血腫脹的鼻腔恢復正常，而達到呼吸順暢的目的。可以紓解因為鼻竇腫脹而引起的不舒服﹑疼痛和呼吸不適。

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ephedrine

pseudoephedrine