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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