The following article was written by user ‘canal_of_schlemm‘ from r/steroids Reddit
Majority of people everywhere have a general idea about what metabolism is, but most have a hard time defining it. Metabolism, by definition, is the net sum of all chemical reactions of the body. We can differentiate metabolic actions based on two classifications: catabolism and anabolism. Catabolic reactions are exergonic reactions that break down complex organic compounds to provide energy. Anabolic reactions are endergonic reactions that synthesize complex molecules from small molecules. The energy exchanged between these two types of reactions requires the use of adenosine triphosphate (ATP).
ATP is a molecule made up of the nucleoside adenosine, a ribose molecule, and three phosphate groups. ATP is unstable and will hydrolyze into adenosine diphosphate (ADP) and a phosphate. We generate ATP through two main mechanisms: substrate-level phosphorylation and oxidative phosphorylation. Substrate-level phosphorylation occurs through many different metabolic processes and consists of the phosphorylation (direct addition of a phosphate group) of AMP or ADP molecules. Oxidative phosphorylation is a process that occurs during aerobic respiration through series of redox reactions in the electron transport chain. Our bodies use ATP for many things that are beyond the scope of this post, so I won’t go in depth into their function. To give you a better idea of the importance of ATP, each cell has about 1 billion ATP molecules which will sustain the cell for less than one minute.
In order to generate ATP, we utilize various metabolic pathways to turn carbohydrates, proteins, and lipids into energy. I will be writing all day if I explained all of the biochemistry behind these processes, so here are the main pathways and their yields:
Carbohydrate metabolism is the main source of ATP in our bodies. We utilize the processes of glycolysis, the tricarboxylic acid cycle, and the electronic transport chain to generate ATP through both substrate-level and oxidative phosphorylation. Glucose is the molecule that undergoes these processes. A six-carbon monosaccharide, glucose is the most simplest form of dietary carbohydrates that our body can utilize. By definition, simple carbohydrates are mono- and disaccharides, and complex carbohydrates are oligo- and polysaccharides. Their ability to be hydrolyzed comes down to the quantity and type of glycosidic linkages between monosaccharides. Our bodies are capable of both catabolic and anabolic reactions regarding glucose. Glycogenesis and gluconeogenesis are two anabolic pathways where glucose is involved. Glycogenesis is the conversion of glucose into glycogen, which is stored in the liver and skeletal muscle. Gluconeogenesis is the conversion of other macromolecules into glucose, specifically amino acids. Catabolic reactions involving glucose would be glycolysis and glygogenolysis. Glycolysis is the conversion of one molecule of glucose into two molecule of pyruvate with the intention of entering the TCA. Under anaerobic conditions, glycolysis can become lactic acid fermentation due to oxygen (which is used as the final electron acceptor in the ETC) being absent. Glycogenolysis is the conversion of glycogen to glucose, typically in order to provide glucose to skeletal muscle during anaerobic conditions. Under ideal conditions, one molecule of glucose can yield 32-34 molecules of ATP utilizing glycolysis, the TCA, and the ETC.
There are many anabolic and catabolic processes regarding lipid metabolism, but we are just going to focus on fatty acid metabolism. We can break this down into the anabolic process of lipogenesis, the deposition of triglycerides in adipocytes, and lipolysis, the breakdown of triglycerides in adipocytes. In ketogenic diets, dietary lipids broken down into monoglycerides and free fatty acids will be utilized in favor of glucose, but that is beyond the scope of this post. In lipogenesis, acetyl-CoA (an intermediate in aerobic respiration) is converted into free fatty acids, which are used to synthesize triglycerides which are stored in adipocytes for future energy needs. There are hormonal influences of where adipogenesis occurs. Likewise, lipolysis is hormone-dependent as well. Triglycerides are broken down into free fatty acids and glycerol through the activation of hormone-sensitive lipase. From here, free fatty acids can undergo the metabolic process of beta oxidation, where carbon-carbon bonds are hydrolyzed to form acetyl-CoA where it can either enter the TCA or be used in ketogenesis to produce acetoacetic acid, beta-hydroxybutyric acid, and acetone. Since fatty acids vary in number of carbon-carbon bonds, their ATP yield can vary, but theoretical yield is approximately 129 molecules of ATP per free fatty acid with 16 carbons.
Fat loss isn’t as simple as calories in vs calories out. Given that metabolism is heavily mediated hormonally and that not all macronutrients are created equally, I do not subscribe to the IIFYM school of thought. Diets like this do not account for the effects of glucagon and insulin on lipogenesis and lipolysis. Here I will discuss the various hormones that have an effect on metabolism:
Insulin is a peptide hormone synthesized and released from the beta cells of the pancreatic islets of Langerhans. Insulin is released in response to elevated blood glucose levels. Insulin binds to insulin receptors on cell membranes and induces translocation of Glut-4 transporters which transports glucose into the cytoplasm. Glycogenesis, gluconeogenesis, lipogenesis, lipolysis, and amino acid uptake are all regulated by insulin. Glycogenesis, lipogenesis, and amino acid uptake are increased and proteolysis, lipolysis, and gluconeogenesis are inhibited by insulin.
Glucagon is a peptide hormones synthesized and released from the alpha cells of the pancreatic islets of Langerhans. Glucagon acts in opposition to insulin. Glucagon is stimulated primarily by low blood glucose concentrations, although ephinephrine and cholecystokinin also stimulate its release. Glucagon is primarily utilized in glycogenolysis, stimulated by second messenger systems and kinase cascades initiated by glucagon binding to glucagon receptors. Similarly, glucagon initiates hormone-sensitive lipase in adipocytes to breakdown triglycerides into free fatty acids.
Epinephrine is a catecholamine synthesized and released in the adrenal medulla and is stimulated by physiologic stress. This is regulated by both the sympathetic nervous system as well as ACTH. Epinephrine binds to adrenergic receptors and can stimulate lipolysis, glycogenolysis, and inhibits glycogenesis. These mechanisms provide increased glucose and free fatty acids in the blood as part of the sympathetic response.
Cortisol is a glucocorticoid steroid synthesized and released in the zona fasciculata or the adrenal cortex. It is in a negative feedback loop with ACTH and CRH. Similar to epinephrine, physiological stress can increase cortisol levels. Cortisol will stimulate gluconeogenesis and glycogenolysis to elevate blood glucose levels. Similarly, cortisol inhibits the Glut-4 translocation initiated by insulin, this is why long term glucocorticoid exposure can lead to type II diabetes. Cortisol will also increase proteolysis, potentially leading to muscle wasting. Adversely, cortisol does have a lipolytic effect, activating hormone-sensitive lipase. This can be seen in patients with Cushing’s disease, where peripheral adipose tissue is minimal while deposition of adipose tissue around the midsection, face, and neck can be increased. This is potentially due to decreased insulin sensitivity, leading to lipolysis to initiate beta oxidation for energy, similar to diabetic ketoacidosis.
Triiodothyronine (T3) is an amino acid-derived hormone that is synthesized and released by follicular cells in the thyroid under stimulation by TSH and TRH. T3, despite not being a steroid hormone, will diffuse into cells and bind to nuclear thyroid hormone receptors. This directly initiates gene expression and protein synthesis. T3 increases basal metabolic rate by increasing synthesis of Na+/K+ ATPase in cells while maintaining normal electrical chemical gradients. Na+/K+ ATPase uses a significant amount of ATP in the body, thus increasing the need for more ATP synthesis. Similarly, T3 increases lipolysis.
Other hormones have a less direct effect on metabolism but are generally well discussed on this sub. Obviously, hGH and estrogen have a large impact on body fat but their effects are typically generated through stimulation of the aforementioned hormones.
Fat loss agents
I am going to address the most commonly used fat loss agents. There are many research chemicals that exist, however, there is a major gap in research explaining their mechanisms and it is a very niche market.
DNP is considered an ionophore, which is a type of lipid soluble molecule that transports ions across a cell membrane. DNP uses this mechanism to interrupt the proton gradient used in oxidative phosphorylation that drives the action of ATP Synthase. By dissipating this gradient in the inner membrane of mitochondria throughout the body, majority of the ATP typically generated through cellular respiration is lost, and the dissipation of the proton gradient is lost as body heat. This is referred to as oxidative phosphorylation uncoupling, which does occur naturally via uncoupling proteins, but nowhere to the extent of the mechanism behind DNP. This excessive heat that is generated can obviously be lethal, as hyperthermia can lead to the unfolding of critical proteins and enzymes in the body. One of the negative effects of DNP is the increase of free intracellular calcium from mitochondria as a result of uncoupling, which increases body temperature and induces spastic paralysis. If this ever occurs, Dantrolene should be administered.
As stated above, exogenous T3 will increase basal metabolic rate by inducing a greater demand for ATP through its expenditure due to T3’s increased synthesis of Na+/K+ ATPase.
Beta-2 adrenergic agonists
Adrenergic receptors are receptors that bind epinephrine and norepinephrine. Alpha-1 and Beta-1 adrenergic receptors produce excitation while Alpha-2 and Beta-2 receptors cause inhibition. In a1 and b1 receptors, binding of epinephrine and norepinephrine will induce smooth muscle contraction, where a2 and b2 receptors will induce smooth muscle relaxation. Beta-2 adrenergic agonists are prescribed to induce bronchodilation in asthmatic patients. When it comes to fat loss agents, clenbuterol and albuterol are used. Albuterol is a short-acting b2 agonist (SABA) and clenbuterol is a long-acting b2 agonist (LABA). Since these agonists are sympathomimetics of epinephrine, their effects will be similar.
Much like beta-2 adrenergic agonists, ephedrine is a sympathomimetic that works by increasing efficacy of norepinephrine on adrenergic receptors.
Buying Fat-Loss Agents
I use email@example.com – they stock DNP, Clenbuterol, T3 and Ephedrine. Shipping to the UK usually takes 1-2 days and they do ship internationally too. Just send them an email explaining that you got their email address from this website and ask for a price list and they will send over a full list of products and prices.