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The complete guide to protein anabolism and catabolism

Der vollständige Ratgeber zum Thema Protein Anabolismus und Katabolismus

This guide includes the following:

  • The exact meaning of the term metabolism.
  • Which are the primary factors that influence catabolism and anabolism.
  • What influence insulin has on protein synthesis.
  • What role nutrition plays in growth hormone, insulin and IFG-1 production.
  • How testosterone plays a significant role in the growth and maintenance of skeletal muscle tissue.
  • The role of the three primary estrogens produced in the human steroidogenesis pathway: Estradiol, estrone and estriol.
  • Why thyroid hormones are a key regulator of human metabolism.
  • Why stress hormones are not something to be avoided/suppressed at all costs.

The two terms thrown around the most in the bodybuilding subculture are "anabolic" and "catabolic". However, I could bet that most people don't know much about these terms beyond the fact that the first term has something to do with building and the second term has something to do with breaking down.

Considering that the primary focus of many competitive and recreational athletes is to improve their body composition, muscle hypertrophy and fat loss are often their primary interests. Therefore, it seems wise to cover the basics of what anabolism and catabolism mean in this context. Furthermore, it is important to understand what these classes of reactions mean in the grand scheme of things for a living organism.

This series of articles is designed to cover the primary factors of the human endocrine system and their role in protein anabolism and catabolism.

What is metabolism?

Metabolism is one of those terms that pretty much everyone knows (and uses) but few really understand, which is why this section will serve to give you a basic idea of what metabolism is exactly.

All living organisms are made up of the simplest living unit - the cell. Yes, this means that even simple microorganisms are "alive", although of course humans are made up of an enormous amount of cells (hundreds of trillions of cells) and are very brain-heavy, whereas many microbes are made up of only a single cell (and have no brain). But I digress...

But back to the topic at hand - chemical reactions are continuously occurring within these cells, consuming or releasing energy as part of the process. These reactions are divided into two classes, which we have already discussed in the introduction: anabolic and catabolic reactions. The former use energy to build cellular components and molecules, while the latter release energy as they break down complex structures.

Therefore, when we speak of metabolism, we are referring to the summation of all these physiological reactions within the cell that are necessary to sustain life. A multitude of variables such as hormonal signals, physical activity, nutrient availability and energy status influence how these reactions occur and when they take place. For now, it is only important that you know that metabolism is a highly intricate system of reactions in cells that sustains life and that there is an inherent energy uptake and an inherent energy release through these processes (hence the need for nutrients).

Improving body composition

The goal of most individuals in the gym is to improve their body composition (i.e. reduce their body fat percentage and/or increase their muscle mass). The complicated part is that improving body composition is a process of give and take. In the bodybuilding and fitness subculture, many people are obsessed with the idea of losing fat and building muscle at the same time.

However, these events are mutually exclusive, at least in theory, as one of the two scenarios requires an energy deficit and the other requires an energy surplus. When I come across one of these trainers or magical programs that guarantee they will help build muscle and lose fat at the same time, I know it's a pretty arrogant claim unless these people or programs manage to overcome the laws of thermodynamics.

One way to think of improving body composition is to swing back and forth between building muscle and losing fat - if you want to increase one of the two, the other must be reduced.

This is why the traditional approach of many gym-goers who want to improve their body composition is to alternate between phases of muscle building and fat loss. This is usually referred to as bulking and dieting. The other option is to be constantly in a maintenance phase (during which you neither gain nor lose muscle or fat). So let's take a look at the role of protein anabolism and catabolism when it comes to improving body composition.

Protein and the development of skeletal muscle tissue

Skeletal muscle tissue serves as the largest reservoir of amino acids in the human body. Many bodybuilders and health enthusiasts love to debate the topic of protein intake - mainly because proteins provide the "building blocks" / amino acids responsible for the synthesis of muscle tissue.

Many people misinterpret the message being sent when someone refers to protein synthesis. Proteins are basically macromolecules that play a variety of roles in humans. They are not only related to muscle tissue, but are ubiquitous in many body systems:

  • Whole body protein turnover - this is a measure of the synthesis and breakdown of all proteins in all organs and body tissues
  • Skeletal muscle protein turnover - this is a measure of synthesis and breakdown in the skeletal muscle area.

If we're looking to improve body composition, then intuitively it should make sense that we're trying to build skeletal muscle tissue specifically, as we're not looking to hypertrophy, say, kidney tissue (well, at least not chronically). Now of course this doesn't mean that whole body protein anabolism is a bad thing (which is ultimately a crucial part of human existence), just that exorbitant whole body protein anabolism over a prolonged period of time can lead to organ enlargement and ultimately health problems.

Synthesis, breakdown, turnover, anabolism, catabolism, hypertrophy... "I'm lost, help!"

Before we continue, for those who find all the technical terms a little confusing, here is a brief overview of some of the terms used in this article:

  • Muscle protein synthesis-Thisterm refers exclusively to the synthesis of protein in skeletal muscle tissue
  • Muscleprotein breakdown-Thisterm refers exclusively to the breakdown of skeletal muscle tissue
  • Protein turnover-Theprotein turnover is a measure of the ratio of protein synthesis to protein breakdown
  • Muscle protein anabolism-Thisterm refers to a condition in skeletal muscle tissue in which muscle protein synthesis exceeds muscle protein breakdown, resulting in a build-up of muscle tissue
  • Muscleprotein catabolism-Thisterm refers to a condition in skeletal muscle tissue in which muscle protein breakdown exceeds muscle protein synthesis, resulting in muscle tissue buildup
  • Hypertrophy-Thisis another term for the growth of tissue (generally with regard to muscle)
  • Atrophy-Thisterm refers to a breakdown of tissue and is the opposite of hypertrophy

Primary hormones and factors to consider with regard to skeletal muscle protein anabolism and catabolism

Okay, now we have arrived at the actual topic of the article and are going to look at the factors that play a major role in protein anabolism and protein catabolism and thus ultimately have an impact on body composition. As previously mentioned, anabolic reactions serve to build cellular components and molecules, while catabolic reactions do the exact opposite. Also, remember that anabolic reactions require an energy input and catabolic reactions release energy. We'll take a more detailed look at what role protein anabolic and protein catabolic reactions play in terms of building skeletal muscle tissue - one of the most important components in improving body composition.

Here is a brief preview of the topics we will be looking at in this context:

  • Amino acid pool, transport and oxidation
  • Insulin
  • Insulin-like Growth Factor-1 (IGF-1) and IGF-Binding Protein-3 (IGFBP-3)
  • Growth hormones
  • Androgenic hormones
  • Oestrogenic hormones
  • Thyroid hormones
  • "Stress hormones" - glucocorticoids, glucagon and catecholamines

Keep in mind that many of the hormones and factors described in this article interact to some degree, making it nearly impossible to isolate these components.

Amino acid pool, transport and oxidation

As mentioned earlier, skeletal muscle tissue serves as the largest reservoir of amino acids in the body and also accounts for the largest mass of protein. There are basically two amino acid pools that are of interest to us: the circulating amino acid pool and the intracellular amino acid pool.

When the body is in a state of starvation (or other catabolic state), amino acids are released from muscle tissue into the bloodstream and used by other body tissues. In contrast, when protein anabolism is necessary, amino acids can be actively transported from the bloodstream into the intracellular space and incorporated into proteins (i.e., new proteins are synthesized).

In addition to the availability of intracellular amino acids, protein synthesis/anabolism is therefore also partly regulated by the transport of amino acids into and out of the cells.

In animals (mainly carnivores), amino acids provide a large amount of energy via the oxidation of amino acids. The oxidation of amino acids to ammonia and their carbon skeletons occurs when excess protein is supplied in the diet or in the presence of starvation, carbohydrate restriction and/or diabetes mellitus.

In humans, ammonia is excreted via the kidneys in the form of urea, while the carbon skeletons of the amino acids are used as substrates of the citric acid cycle for the purpose of energy production. Some people claim that increased kidney stress from high protein intake is against traditional bodybuilding diets, but even protein levels above four grams per kilogram of body weight appear to be safe and harmless for people with healthy kidney function (although this may be a rather exorbitant amount of protein for most exercisers).


Insulin is a peptide hormone secreted by the pancreas primarily in response to elevated blood glucose levels (as it upregulates the activity of glucose transport molecules). Unfortunately, thanks to the dramatic rise in type 2 diabetes in the Western world, insulin is generally considered the enemy of human physiology as we know it.

However, I can assure you that if your goal is to build a lean and muscular body, you would be well advised to let insulin work its anabolic magic rather than trying to avoid insulin spikes at all costs, as some carbohydrate opponents advocate.

Insulin is one of the most potent anabolic hormones in the human body and induces body-wide anabolism when amino acids are supplied. The key here is that a state of hyperinsulinemia (elevated insulin levels) without concomitant amino acid availability does not appear to increase total body protein synthesis (even though insulin reduces the body-wide rate of protein breakdown in this scenario) (1,2,3).

However, even though insulin reduces body-wide protein breakdown, it does not modulate the ubiquitin system, which is responsible for regulating muscle protein breakdown. Thus, insulin does not specifically reduce muscle protein breakdown (4).

Scientific studies suggest that insulin does not directly alter the transmembrane transport of most amino acids, but instead increases muscle protein synthesis by utilizing the active intracellular amino acid pool (5). The exception to this is amino acids that use sodium-potassium pumps (primarily alanine, leucine and lysine), as insulin causes hyperpolarization of muscle cells by activating these pumps (2).

This suggests that elevated insulin levels in combination with elevated plasma amino acid levels should be quite conducive to promoting muscle protein synthesis. Indeed, this is the reason that patients in a critical state of cachexia (generalized physical decline) often receive an infusion of amino acids and insulin.

Insulin Summary:

All the scientific hoopla can sometimes cause us to lose sight of the big picture. The bottom line of this section is that insulin is indeed a highly anabolic hormone that is conducive to skeletal muscle protein synthesis, but exogenous (external) amino acid delivery is necessary to elicit this effect.

As mentioned earlier, a state of hyperinsulinemia (i.e. elevated insulin levels) and hyperaminoacidemia (i.e. elevated plasma amino acid levels) will promote protein synthesis, and what better way to create such a state than to consume protein and carbohydrates in combination.

However, you should be careful not to take the message as "the more insulin the better", which does not seem to be the case in physiological terms. Scientific research seems to suggest that even though some insulin will increase the muscle protein synthesis response to a food intake, there is a point of satiety beyond which further increases in insulin levels will not cause a greater increase in protein synthesis (6).

Many people believe that a superfluous boost of fast-acting carbohydrates in combination with whey protein - especially post-workout - is ideal to maximize the muscle protein synthesis response. The reality is that you don't need insulin spikes - a weak and transient insulin response (as seen with low-glycemic carbohydrates) will provide pretty much the same muscle protein synthesis benefits as a rapid massive insulin response.

Insulin-like Growth Factor-1 (IGF-1) & IGF-Binding Protein-3 (IGFBP-3)

As the nomenclature suggests, IGF-1 is a peptide hormone that is quite similar in structure to insulin and has effects on human growth. IGF-1 is mainly produced in the liver following the docking of growth hormones and acts locally in certain tissues or systemically (body-wide). Thus, IGF-1 is a mediator for the effects of growth hormones. IGF-1 is a potent inhibitor of the AKT signaling pathway within cells, which has effects on cell growth and maturation.

For practical purposes, it is important to consider the actions of IGFBP-3 because almost all IGF-1 is bound to one of the 6 protein complexes and IGFBP-3 accounts for 80% of all such binding.

IGF-1 is believed to have similar effects to insulin on protein metabolism due to its ability to bind to and activate the insulin receptor, although the effect of IGF-1 at these receptors is significantly weaker than insulin itself (about 1/10th of the effect) (7).

Thus, it is not surprising that IGF-1 increases protein anabolism in skeletal muscle and throughout the body (8,9). A unique property of IGFBP-3 is that it appears to inhibit skeletal muscle atrophy (i.e., it is anti-catabolic (10).

IGF-1/IGFBP-3 Summary:

Considering that IGF-1/IGFBP-3 are useful in terms of stimulating protein synthesis and maintaining skeletal muscle tissue during periods of muscle wasting/cachexia, the question most are likely asking is "How do I increase circulating levels of these compounds?"

Well, there are several factors that influence the amount of IGF-1/IGFBP-3 (and growth hormones) present in the blood at any given time. These include genetic predisposition, biorhythm, age, training, nutritional status, stress, health status and ethnicity.

Many people assume that an increase in insulin levels may interfere with a subsequent increase in IGF-1 levels, but this is not the case (remember that insulin and IGF-1 are structurally and functionally similar in some ways, but they are produced in different ways). Since an increase in growth hormone levels ultimately leads to the production of IGF-1 (roughly 6 to 8 hours after growth hormone release), it intuitively makes the most sense to focus on increasing endogenous growth hormone levels (which we will look at in the section on growth hormones).

*Quick side note on supplements: Deer Antler Velvet Supplements and other supplements that claim to increase endogenous IGF-1 levels by containing natural IGF-1:

In recent years, some supplement manufacturers have made the claim that products such as Deer Antler Velvet (deer antler extract) can promote muscle growth due to the high levels of IGF-1 naturally contained in these extracts. However, in reality, such products are completely ineffective as IGF-1 is a peptide hormone and is completely destroyed in the digestive tract when taken orally. Apart from that, such complex peptides cannot be absorbed into the body via the digestive tract.

In the second part of this article, we will take a closer look at the influence of growth hormones, androgens, oestrogens, thyroid hormones and stress hormones on protein metabolism.


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