We know that all proteins are collections of amino acids. Said another way, amino acids are the “building blocks” of proteins. Al¬though the final functional form of some proteins may contain minerals or other nonprotein components, the basis for these proteins is still amino acids. However not all amino acids are used to build protein by humans and other lifeforms. Let’s dig in on amino acids.

All amino acids have the same basic design, as shown in Figure 1. There is both a nitrogen-containing amino portion and carbox¬ylic acid portion attached to a central carbon atom. The presence of both an amino and an acid portion on each molecule led to the name amino acid for this family of molecules. There is also a hydrogen atom attached to the central carbon, as well as a “side group” often designated with a “R”.

The side group denotes the portion of an amino acid that will be different from one amino acid to the next. The side group portion of an amino acid may be as simple as a hydrogen atom, as in glycine, or much more complex to include carbon chains and rings, acid or base groups, and even sulfur (S). The structure of the twenty amino acids used to make protein is shown in Figure 2.

There are probably hundreds of different amino acids found in nature, but only twenty are incorporated into the proteins found in living things (see Table 1). This means that these twenty amino acids are the basis of protein found in birds, lizards, plants, bacteria, fungi, yeast, and so on. This is a very profound and convenient situation. First, it allows us to further appreciate that, despite the obvious structural and functional differences between the different life-forms on this planet, there is common ground and more than likely common ancestry. Second, it somewhat simplifies human protein nutrition as we can obtain all the amino acids we need to make our body proteins by eating the proteins of other life-forms.

Some proteins contain just a few amino acids linked together, while others contain hundreds of amino acids. Scientists often refer to the links of amino acids in the following manner:

• Peptides are two to ten amino acids including dipeptides, tripeptides, etc.
• Polypeptides are 11 to 100 amino acids.
• Proteins are > 100 amino acids.

Other scientists will describe protein size based upon the weight of the protein molecule (molecular weight) and sometimes use the term Daltons as a unit of weight. When we discuss proteins, we will only refer to protein size and design only if its helps us understand a protein’s unique function.

Individual amino acids can be used to make certain hormones and neurotransmitters such as epinephrine, serotonin, norepinephrine, and thyroid hormone (see Table 2). In fact, most neurotransmitters are derived from amino acids. Amino acids are also used to make other important substances such as creatine, choline, carnitine, nucleic acids, and the vitamin niacin. Last, amino acids can be used by some tissue as an energy source or can be converted to glucose or fat depending upon our current nutritional/metabolic state (i.e., fasting, fed, exercise).

The goal of protein digestion is to disassemble proteins to their constituent amino acids and smaller peptides that can be absorbed. Protein digestion begins in our stomach as swallowed food is bathed in the acidic juice. In fact, the presence of protein/amino acids along with distension of the stomach causes stomach juice to ooze from glands in the wall of the stomach. The acid serves to straighten out the complex three-dimensional design characteristic of many proteins. Scientists refer to this as denaturing the protein or changing its natural 3-dimensional design. This will make it easier for protein-digesting enzymes in the stomach and small intestine to do their job. This is analogous to straightening out a ball of yawn so that you easily can cut small lengths.

An enzyme called pepsin is found in stomach juice and begins to break the bonds between amino acids. The impact of pepsin is significant yet incomplete, as most of the bulk of protein digestion takes place further along in the small intestine. As partially digested proteins make their way into the small intestine, a battery of protein-digesting enzymes attack and break down protein into very small amino acid links and individual amino acids. Most of these enzymes come from the pancreas and include trypsin, chymotrypsin, carboxypeptidase A and B, elastase, and collagenase. These enzymes are made, packaged, and released by our pancreas in an inactive form. It is not till they reach the small intestine that these enzymes are activated by another enzyme produced by the small intestinal called enterokinase (enteropeptidase). The reason for this complex system is to protect the pancreas and the duct that connect to the stomach from the protein-digesting activity of these enzymes.

Amino acids are taken up by the cells that line the small intestine, then move out of the backside of those cells and enter the bloodstream. Meanwhile, small peptides, consisting of just a couple or a few amino acids linked together can also be brought into these cells where final digestion to amino acids will take place. Therefore, generally, the absorbed form of protein will be individual amino acids. Fragments of proteins can also be absorbed and are important in developing the immune system during infancy as well as are linked to many food allergies reactions.

Once absorbed, amino acids can enter circulation via the portal vein, which delivers the amino acids to our liver first, before flowing into the general circulation. In fact, it is typical for only about one-fourth of the absorbed amino acids to circulate beyond the liver, including a disproportionate level of the branched-chain amino acids (BCAAs), namely leucine, isoleucine, and valine. This is likely due the essential amino acids, and in particular leucine, play a key role in ensuring that protein manufacturing throughout the body is increased to help meet the protein needs of each cell and tissue to which they belong. This also helps replace the BCAAs used for energy if it has been several hours since a previous protein-meal (e.g., overnight).

For people who exercise, it will help replace those amino acids, like BCAAs, which is used for energy during endurance training/competition, as well as support protein manufacturing during recovery from any type of hard exercise. BCAAs have long been a popular supplement for athletes worldwide. Moreover, essential amino acids (EAAs), which BCAAs are a component are also popular and can have some advantages over BCAAs alone with certain applications.

Amino acids entering the body can play several roles, however the most obvious will be to serve as building blocks for protein manufacturing. In addition, some amino acids are used to make other important substances like creatine, carnitine, glutathione, and certain hormones and neurotransmitters. Amino acids circulate, enter and exit cells, and collectively only about one percent of the total amino acids are not part of protein. Said differently, 99 percent of the amino acids in the body are part of proteins.

Free amino acids are found in the body because of digestion of food protein liberates amino acids for absorption into the body from the digestive tract. In addition, amino acids are liberated as body proteins are broken down daily. Free amino acids account for about one percent of the amino acids in our body, while the remaining 99 percent of amino acids are components of body peptides and proteins. Most cells in the body have a small assortment of free amino acids, meaning they are independent and not linked to other amino acids as part of peptides and proteins. In addition, there is a small amount of amino acids circulating in the blood which, although this increases after a protein containing meal and wanes as amino acids enter tissue.

Circulation provides a deliver system for diet derived amino acids to get to all tissue as well as a means for amino acids to be exchanged between tissue such as during fasting and exercise. Free amino acids in cells and in the blood are collectively referred to as the “amino acid pool” and these amino acids are available to make new body protein or amino acid-derived substances (e.g. neurotransmitters, hormones, metabolic factors, etc.).

Amino acids that enter our blood from our digestive tract promote a release of insulin from our pancreas. This is especially true for the BCAAs (leucine, isoleucine, valine) and threonine. In addition, some partially digested protein fragments can also increase insulin release as well. However, the ability of elevated blood amino acid concentrations to cause the release of insulin is nowhere near as potent as elevation in blood glucose. Regardless, the increased presence of circulating insulin will promote the uptake of amino acids in certain tissue, including muscle, as well as promoting a net positive protein balance whereby protein production exceeds breakdown. Here, the main effect of insulin is to lower muscle protein breakdown over promoting synthesis.

The increase in insulin will help lower circulating glucose levels after a meal. Thus, amino acids, and some peptides derived from food proteins, can have a glycemic lowering effect.

The increase in the level of circulating amino acids after a meal can slightly increase the level of glucagon as well. Considering this, aren’t the actions of insulin and glucagon opposite, thus making this scenario counterproductive? Consider the following scenario from our distant past. What if our sole source of food was animal flesh? Having the effects of insulin and glucagon would allow the conversion of some amino acids to glucose in the liver while insulin would promote the formation of glycogen and muscle protein as well as promote the production and storage of some fat if enough protein is consumed. All these efforts would leave that person in better shape for enduring an extended period of time before they ate again. This certainly may have been the case for our distant ancestors when enduring winters or prolonged dry seasons when vegetation might not have been available.

Amino acids from diet protein, exceeding the immediate needs of cells throughout the body are not stored as protein. Said differently, once the more immediate needs for amino acid needs of cells to make proteins and other non-protein substances, like creatine, epinephrine, serotonin, etc., reserves are not made as a matter of metabolic efficiency. So, unlike fat, we do not store excessive diet protein as body protein. So, what does happen? Much of the answer lies in what else is being eaten as well as the nourishment state of the body.

Different amino acids can have different fates, however all 20 amino acids that serve as building blocks for protein can be used for energy purposes. Said differently, protein derived amino acids are broken down and eventually feed into the same energy systems as carbohydrate and fat. However, along the way, some amino acids can be used to make glucose and/or ketones. So, the outcome will be based on additional factors such as what else is being eaten, and whether amino acids need to be converted to other energy nutrients first. We will talk about different scenarios when we talk about protein supplements or ketogenic diets, etc.

One additional consideration is whether the excess protein is part of mixed food meals. In this scenario, digestion, and absorption of all the protein would take place over a longer period of time. This allows opportunity for more of the protein derived amino acids to be used to make body protein or other vital substances. Also, some amino acids will still be used for energy, so in this case it could take the place of some fat. Over time this could contribute to increases in body fat but only if caloric intake consistently exceeded expenditure during that time. Meanwhile the true efficiency of converting dietary protein to body fat is still debated and numerous considerations.