Nutrient Transport

What is nutrient transport?

Simply put, nutrient transport requires numerous complex systems to move and deliver nutrients to their intended destinations throughout the mind and body.

Nutrient transport systems are vital and complex however, the purpose of this page is to merely introduce you to a component of human nutrition you probably never heard about.

Why should you care? If you are like most, you continue to spend a lot of money on “healthy foods” and supplements to the point of frustration looking for results. If so, this page will be helpful. Read on.

Nutrient transport systems do not detract from the critical importance of Nutrient Interrelationships that remain applicable for the complexity of nutrient transporters as well.

However, before we begin, because the terms nutrient transport or transporters may be unfamiliar, a commonly known and promoted term in nutritional supplement marketing is absorption. It is a tremendous marketing hook, and you constantly hear claims such as “our supplements are the most scientifically proven absorbable nutrients! Malabsorption is also a familiar term that may easily associated with nutrient transporters as well.

Albeit properly formulated supplements do increase the potential for absorption, don’t be completely misled by such claims. Here’s why,

Simply put, if you DO NOT have the nutrient transporter, cotransporters or any combination of the nutrient transport system for any particular nutrient, you have NO absorption of that nutrient! Yes, it is that simple.

To begin, all nutrients require some means of transport to move from one place to another once they enter the body.

For example, as in our society, we have multiple means available to transport people or products from one place to another. Transport Systems include cars, trucks, planes, boats, trains, pipelines, animals, rivers, and so on as well as a combination of as many transporters (and cotransporters) as needed.

In the world of human nutrition, as in our society, nutrient transport systems are needed to move and deliver nutrients to specific places throughout the mind and body. Also, in the same manner as society, there are many diverse types of transporters, and each nutrient requires a specific transporter or combination of specific transporters. Hence, nutrient transport systems.

Obviously, blood is the major transporter for all products (i.e., nutrients, hormones, waste products and so on) throughout the mind and body. However, we must ask, how did a nutrient enter the blood stream? If it was consumed orally, numerous transporters are located throughout the digestive tract that are required to transport each nutrient into the blood stream.

Keep in mind, once a nutrient is successfully transported into the blood stream (which is the first step and extremely important!), it now must be transported into the cell because we live and die at the cell level.

Note: To reiterate, nutrient transport systems are extremely complicated and would require an enormous amount of information on this page in an effort to explain to any degree. As such, my aim is to simply introduce you to one of the most vital components of human nutrition.

Even if you consume a diet based explicitly on nutrient interrelationships, it will not be as successful as desired if you do not have the exact transporter/s required for each nutrient to be absorbed into the bloodstream and then into the cell for cellular absorption and thus, cellular utilization.

Nutrient transporters are commonly referred to as families!

First, there are many distinct types of transporters, and each type contains additional transporters and cofactors. As such, nutrient transporters are grouped into different families that are classified under several different headings based on the structure, actions, or methods of transport for each independent transporter.

For example, transporters use different means for transport that includes;

• The ATPase Family of Transporters
• E-type ATPases
• F-type ATPases
• P-type ATPases
• V-type ATPases
• A-type ATPases (numerous A-type ATPases family members)
• Na+/K+-ATPases
• Ion Channels (numerous Ion Channels family members)
• Ligand-Gated Ion Channels (numerous Ligand-Gated Ion Channel Family Members)
• Calcium Channels and Transporters
• Voltage-Gated Calcium Channels
• Cav1 Family
• Cav2 Family
• Cav3 Family
• Calcium Release Channels
• Calcium Reuptake Transporters
• Potassium Channels
• Voltage-Gated Potassium Channels (Table of the Voltage-Gated Potassium Channels)
• The ABC Family of Transporters (Table of ABC Family Transporters)

As you can see from this truly short preview sourced from The Medical Biochemistry Page, Biological Membranes and Membrane Transport Processes, https://themedicalbiochemistrypage.org/biological-membranes-and-membrane-transport-processes/#slc, the complexity of nutrient transporters becomes evident very quickly.

This is an excellent website that I recommend investigating, even if it is for a short amount of time, to gain a true understanding of the complexity of nutrient transporters that are essential to human nutrition. Simply scroll through the site for 10-seconds just to see what this is about!

What you just reviewed is actually the simpler aspect of nutrient transporters. Now for the rabbit hole. When you investigate the transporter proteins, the Solute Carrier Group (SLC, aptly described as a superfamily), the genius of human nutrition now boggles the mind.

Briefly explained, a SLC protein may, depending on the nutrient to be transported, may consist of several amino acids, let’s say ten, and these amino acids are strictly and specifically sequenced from 50 to 2,000 or more times (e.g., the sequence would look like: ABECAADDEAACCBACFFCCAB and so on throughout the completed specific sequence). Some proteins are known to be sequenced up to 5,000 times! Of extreme importance is that if any amino acid is not in the proper position sequentially for any specific transporter, it makes the transporter ineffective!

In this article, the role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson’s diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenerative disorders.

Ayka A, Şehirli AÖ. The Role of the SLC Transporters Protein in the Neurodegenerative Disorders. Clin Psychopharmacol Neurosci. 2020 May 31;18(2):174-187. doi: 10.9758/cpn.2020.18.2.174. PMID: 32329299; PMCID: PMC7236796. https://pubmed.ncbi.nlm.nih.gov/32329299/

Note: There are several different protein types that include antibodies, contractile proteins, enzymes, hormonal proteins, structural proteins, storage proteins, and transport proteins. We are referring to transport proteins on this page.

Membrane transporter proteins are encoded by numerous genes that can be classified into several superfamilies, on the basis of sequence identity and biological function.

Sadée W, Drübbisch V, Amidon GL. Biology of membrane transport proteins. Pharm Res. 1995 Dec;12(12):1823-37. doi: 10.1023/a:1016211015926. PMID: 8786953. https://pubmed.ncbi.nlm.nih.gov/8786953/

What do nutrient transporters actually do?

To briefly reiterate, they transport nutrients throughout the mind and body where they need to be. Every nutrient entering the body requires some form of transport system or systems to enter into the bloodstream and then into the cell.

Nutrient transporters are solely responsible for nutrient absorption (especially at the cell level)! However, nutrient interrelationships are pivotal for synergistic relationships and cofactors required to facilitate absorption. As such: here is a simple formula:

Nutrient Interrelationships + Nutrient Transporters = Nutrient Absorption

Nutrients entering the body orally (foods, liquid, supplements, etc.) and digested properly in the stomach, require different transporters to enter the blood stream. Absorption into the bloodstream during the digestive process is the first level or the absorption phase. Absorption at this level is extremely competitive due to the competition between nutrients, naturally occurring substances (e.g., phytates, oxalates, etc.), toxins (elements and chemical), and so on.

For example, folate/thiamine transporters in the Solute Carrier Group include SLC19A1, SLC19A2, SLC19A3 and perform the following,

• SLC19A1: cellular uptake of reduced folate and thiamine mono- and di-phosphate but not free thiamine
• SLC19A2: intestinal uptake of thiamine
• SLC19A3: cellular uptake of thiamine; mutations in gene associated with a Wernicke-like encephalopathy

Absorption into the bloodstream also occurs by other means than the digestive tract such as through the lungs when you breathe, skin absorption (e.g., topical, transdermal, etc.), shots, suppositories, and so on. Regardless of the point of entry, these nutrients also require transporters.

SLCs are responsible for transporting extraordinarily diverse solutes across biological membranes, including inorganic ions, amino acids, lipids, sugars, neurotransmitters and drugs. Most of these membrane proteins function as coupled symporters (co-transporters) utilizing downhill ion (H+ or Na+) gradients as the driving force for the transport of substrate against its concentration gradient into cells.

Bai X, Moraes TF, Reithmeier RAF. Structural biology of solute carrier (SLC) membrane transport proteins. Mol Membr Biol. 2017 Feb-Mar;34(1-2):1-32. doi: 10.1080/09687688.2018.1448123. Epub 2018 Apr 13. Erratum in: Mol Membr Biol. 2017 Feb – Mar;34(1-2):65. PMID: 29651895. https://pubmed.ncbi.nlm.nih.gov/29651895/

Cellular transport – the ultimate goal for cellular health!

We live and die at the cellular level! Therefore, all but a limited few of the nutrients absorbed into the bloodstream now require various and specific transporters and mechanisms to actually enter into the cell for cellular health.

At this point, we must keep in mind that many factors are involved for nutrient absorption into the cell. However, a crucial factor includes the integrity and permeability of the cell membrane. The cell membrane is another complex subject in and of itself. Frankly, I don’t believe there is anything simple involving human nutrition!

One of the functions of the cell membrane is to provide an optimal level of resistance for permeability into or out of the cell. The permeability of the membrane (membrane potential – electrical) is a function of the Na/K ATPase (commonly referred to as the sodium-potassium pump) that maintains a gradient electrical charge on the membrane. Interestingly, sodium, potassium, and the sodium-potassium pump are also well recognized nutrient transporters independently.

However, if the membrane integrity is compromised (especially excesses and deficiencies of sodium or potassium that also effect function of the sodium-potassium pump; Na/K ATPase), it will not provide the optimal level of resistance for proper permeability and the result will be that nutrients (hormones, waste products, etc.) may either enter the cell too easily or that nutrients are facing too much resistance for entry.

The sodium and potassium levels are subject to excesses and deficiencies during various stages of stress. As such, the sodium-potassium ratio becomes imbalanced which may interfere with effectiveness of the sodium-potassium pump and therefore, cell permeability.

There are a handful of crucial ions which contribute to the resting potential, with sodium (Na+) and potassium (K+) providing a dominant influence. Various negatively charged intracellular proteins and organic phosphates that cannot cross the cell membrane are also contributory. To understand how the resting membrane potential gets generated and why its value is negative, it is crucial to have an understanding of equilibrium potentials, permeability, and ion pumps.

Steven M. Chrysafides; Stephen J. Bordes; Sandeep Sharma, Physiology Resting Potential, Last Update: April 14, 2022.  https://www.ncbi.nlm.nih.gov/books/NBK538338/

Remember, I mentioned a limited few nutrients do not require specific transporters to enter the cell. That is because of passive transport. This simply means that the nutrient is absorbable into the cell without assistance. However, the permeability of the cell membrane is important for passive transport.

Cell membrane integrity is a completely different topic; however, it is another critical component of nutrition because it affects nutrient/hormone entry due to the functions of cellular receptors as well as the removal of waste products from the cell.

Note: I am certain you notice I use several different adjectives throughout this website in an effort to establish some form of hierarchy of importance to the topic at hand. The reality is that every detail of every topic on this website is of equal importance!

Nutrient Transporters – blood analysis or cellular analysis?

First, due to the diverse types and structures of transporters, various analyses would be required for different transporters per se. In this instance, we are addressing transporters that are associated with and dependent on a variety of elements revealed in our analysis.

Transporters for vitamin C and its oxidized form dehydroascorbic acid (DHA) are crucial to maintain physiological concentrations of this important vitamin that is used in a variety of biochemical processes. The human SLC23 family consists of the Na(+)-dependent vitamin C transporters SVCT1 (encoded by the SLC23A1 gene) and SVCT2 (SLC23A2) as well as an orphan transporter SVCT3 (SLC23A3).

Bürzle M, Suzuki Y, Ackermann D, Miyazaki H, Maeda N, Clémençon B, Burrier R, Hediger MA. The sodium-dependent ascorbic acid transporter family SLC23. Mol Aspects Med. 2013 Apr-Jun;34(2-3):436-54. doi: 0.1016/j.mam.2012.12.002. PMID: 23506882. https://pubmed.ncbi.nlm.nih.gov/23506882/

As seen, just because a nutrient may be present in the blood, it does not necessarily mean that it is present in the cell or at the proper cellular level (nutrient excesses and deficiencies). In addition, many nutrients such as magnesium and potassium are intracellular which means the majority exists inside the cell – not in the blood.

Also, nutrients such as calcium are tightly regulated to maintain a specific level in the blood. This is known as homeostasis.

As such, what does a blood analysis reveal for cellular nutrient status? Basically, the blood simply reveals the presence of nutrients in the blood that should be available for cellular transport. How do you know your cells are properly nourished?

Let us look at two examples.

Interestingly, valuable information that may be garnered by comparing a blood and cellular analyses is that, in both examples, one may be experiencing a transporter problem. For instance, if a blood analysis reveals a high level of any of these nutrients in the examples yet a cellular analysis reveals a deficiency, it may indicate a potential transporter problem.

How can hair analysis help with transporters?

Our hair analysis can be a very useful tool that may help reveal the potential for nutrient transporter problems. As seen in the ABC transport group, many transporters consist of elements analyzed in our hair analysis.

In addition, several elements tested (calcium, sodium, potassium, zinc) are important for the parietal cells in the stomach to produce hydrochloric acid. Your stomach must maintain the proper pH level (e.g., 1-3.5 pH) for the proper digestion of foods that provide the nutrients required (especially amino acids for the SLC group) and by other transporters previously mentioned.

Also, sodium, potassium, and the sodium/potassium ratio (Na/K ATPase) are important transporters individually and in conjunction with other nutrients to produce additional types of nutrient transporters. Remember the importance of the sodium/potassium pump (Na/K ratio) for cell permeability.

In addition, as seen in nutrient interrelationships, many of the elements analyzed in our hair analysis are important cofactors required by other nutrients (vitamins, amino acids, fatty acids, and derivatives) to function and are required by many different transporters as well as cellular membrane health.

Note: This is an extremely condensed page about the enormity of science about nutrient transporters. This page (and website) is intended to reveal the overwhelming complexity of human nutrition that cannot be overstated.

Every aspect of today’s world further contributes to this complexity; however, you can overcome many of today’s pitfalls with truthful information and the use of nutritional testing through laboratory means! Remember,

If you are not testing, you are guessing!

Would you like some insight into many of your nutrient transporters?

Click here to Order Your Hair Analysis Today!

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REFERENCES – NUTRIENT TRANSPORTERS

Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy of the chemical gradient of another molecule (secondary transport). Primary transporters include the rotary motor ATPases (F-, A-, and V-ATPases), P-type ATPases and a large family of integral membrane proteins referred to as “ABC” (ATP binding cassette) transporters. (“Structure and mechanism of ABC transporters – PubMed”)

Wilkens S. Structure and mechanism of ABC transporters. F1000Prime Rep. 2015 Feb 3;7:14. doi: 10.12703/P7-14. PMID: 25750732; PMCID: PMC4338842. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338842/

In this review, we will describe how the Na+/K+ ATPase maintains a Na+ gradient utilized by multiple sodium-dependent transport mechanisms to regulate glucose uptake, excitatory neurotransmitters, calcium signaling, acid-base balance, salt-wasting disorders, fluid volume, and magnesium transport. We will discuss how several Na+-dependent cotransporters and Na+-dependent exchangers have significant roles in human health and disease. Finally, we will discuss how each of these Na+-dependent transport mechanisms have either been shown or have the potential to use Na+ in a secondary role as a signaling molecule. (“Sodium Transporters in Human Health and Disease – PubMed”)

Gagnon KB, Delpire E. Sodium Transporters in Human Health, and Disease. (“Risk factors for hyponatremia in acute exacerbation chronic obstructive …”) Front Physiol. 2021 Feb 25;11:588664. doi: 10.3389/fphys.2020.588664. PMID: 33716756; PMCID: PMC7947867. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947867/

The resting membrane potential is the result of the movement of several different ion species through various ion channels and transporters (uniporters, cotransporters, and pumps) in the plasma membrane. These movements result in different electrostatic charges across the cell membrane. (“Physiology, Resting Potential – PubMed”)

Chrysafides SM, Bordes SJ, Sharma S. Physiology, Resting Potential. [Updated 2022 Apr 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538338/

In this review, we present an overview of these mechanisms and the growing evidence that the lipid bilayer is a major determinant of the fold, form, and function of membrane transport proteins in membranes.

Ernst M, Robertson JL. The Role of the Membrane in Transporter Folding and Activity. J Mol Biol. 2021 Aug 6;433(16):167103. doi: 10.1016/j.jmb.2021.167103. Epub 2021 Jun 15. PMID: 34139219; PMCID: PMC8756397. https://pubmed.ncbi.nlm.nih.gov/34139219/

SLC transporters serve as ‘metabolic gate’ of cells and mediate the transport of a wide range of essential nutrients and metabolites such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation… SLCs contribute to the transmembrane transport of various substrates such as inorganic ions, amino acids, fatty acids, neurotransmitters, and saccharides.

Yong Zhang, Yuping Zhang, Kun Sun, Ziyi Meng, Ligong Chen, The SLC transporter in nutrient and metabolic sensing, regulation, and drug development, Journal of Molecular Cell Biology, Volume 11, Issue 1, January 2019, Pages 1–13, https://doi.org/10.1093/jmcb/mjy052

The SLC superfamily does not contain active transporters that directly use the energy released by ATP hydrolysis to drive the transport of substances against their concentration gradient. Rather, these proteins act as passive facilitative transporters or secondary active transporters.

Pizzagalli, M.D., Bensimon, A. and Superti-Furga, G. (2021), A guide to plasma membrane solute carrier proteins. FEBS J, 288: 2784-2835. https://doi.org/10.1111/febs.15531

There have been several recent discoveries of new transporters that likely contribute to the absorption of oligopeptides and fatty acids. In addition, details are being clarified about how transporters work and in what forms nutrients can be absorbed. The enzymes that digest basic carbohydrates, proteins, and fats have been identified in various segments of the GI tract, and details are becoming clearer about what types of bonds they hydrolyze.

Goodman BE. Insights into digestion and absorption of major nutrients in humans. Adv Physiol Educ. 2010 Jun;34(2):44-53. doi: 10.1152/advan.00094.2009. PMID: 20522896. https://pubmed.ncbi.nlm.nih.gov/20522896/

Because of the key functions of thiamin, uptake and transport through the body are crucial. Its uptake route is relatively complex, encompassing a variety of protein families, including the solute carrier anion transporters, the alkaline phosphatase transport system, and the human extraneuronal monoamine transporter family, some of which are multispecific proteins.

Biochemistry 2014, 53, 5, 821–835, Publication Date:January 24, 2014,https://doi.org/10.1021/bi401618y, Copyright © 2014 American Chemical Society

Intestinal transport and sensing processes and their interconnection to metabolism are relevant to pathologies such as malabsorption syndromes, inflammatory diseases, obesity and type 2 diabetes. Constituting a highly selective barrier, intestinal epithelial cells absorb, metabolize, and release nutrients into the circulation, hence serving as gatekeeper of nutrient availability and metabolic health for the whole organism. Next to nutrient transport and sensing functions, intestinal transporters including peptide transporter 1 (PEPT1) are involved in the absorption of drugs and prodrugs, including certain inhibitors of angiotensin-converting enzyme, protease inhibitors, antivirals, and peptidomimetics like β-lactam antibiotics.

Zietek Tamara, Giesbertz Pieter, Ewers Maren, Reichart Florian, Weinmüller Michael, Urbauer Elisabeth, Haller Dirk, Demir Ihsan Ekin, Ceyhan Güralp O., Kessler Horst, Rath Eva, Organoids to Study Intestinal Nutrient Transport, Drug Uptake and Metabolism – Update to the Human Model and Expansion of Applications, Frontiers in Bioengineering and Biotechnology, VOLUME=8, 2020; DOI=10.3389/fbioe.2020;577656 ISSN=2296-4185 https://www.frontiersin.org/articles/10.3389/fbioe.2020.577656