Metabolites and their potential use for Human Augmentation

Guido Putignano
Yealthy
Published in
8 min readSep 15, 2022

Metabolites:

Asubstance is a product of metabolic action or that is involved in a metabolic process. A metabolite refers to any substance involved in metabolism. It is often regarded as the immediate by-product of a metabolic process. However, some references consider those involved in a metabolic reaction (not necessarily a by-product) as a metabolite. Metabolites are biomolecules that are relatively smaller in size than large biomolecules (e.g. proteins and nucleic acids). They are naturally occurring. However, they can be produced artificially for industrial and pharmaceutical uses.

Metabolites can be categorized into both primary and secondary metabolites. These metabolites can be used in industrial microbiology to obtain amino acids, develop vaccines and antibiotics, and isolate chemicals necessary for organic synthesis.

Primary Metabolites:

Primary metabolites are involved in the growth, development, and reproduction of the organism. The primary metabolite is typically a key component in maintaining normal physiological processes; thus, it is often referred to as a central metabolite. Primary metabolites are typically formed during the growth phase as a result of energy metabolism and are deemed essential for proper growth. Examples of primary metabolites include alcohols such as ethanol, lactic acid, and certain amino acids. Within the field of industrial microbiology, alcohol is one of the most common primary metabolites used for large-scale production. Specifically, alcohol is used for processes involving fermentation which produce products like beer and wine. Additionally, primary metabolites such as amino acids– including L-glutamate and L-lysine, which are commonly used as supplements– are isolated via the mass production of a specific bacterial species, Corynebacteria glutamicum. Another example of a primary metabolite commonly used in industrial microbiology includes citric acid. Citric acid, produced by Aspergillus niger, is one of the most widely used ingredients in food production. It is commonly used in the pharmaceutical and cosmetic industries as well.

Secondary Metabolites:

Secondary metabolites are typically organic compounds produced through the modification of primary metabolite synthases. Secondary metabolites do not play a role in growth, development, and reproduction like primary metabolites do and are typically formed during the end or near the stationary phase of growth. Many of the identified secondary metabolites have a role in ecological function, including defense mechanism(s), by serving as antibiotics, and by producing pigments. Examples of secondary metabolites with importance in industrial microbiology include atropine and antibiotics such as erythromycin and bacitracin. Atropine, derived from various plants, is a secondary metabolite with important use in the clinic. Atropine is a competitive antagonist for acetylcholine receptors, specifically those of the muscarinic type, which can be used in the treatment of bradycardia. Antibiotics such as erythromycin and bacitracin are also considered to be secondary metabolites. Erythromycin, derived from Saccharopolyspora erythraea, is a commonly used antibiotic with a wide antimicrobial spectrum. It is mass-produced and commonly administered orally. Lastly, another example of an antibiotic that is classified as a secondary metabolite is bacitracin. Bacitracin, derived from organisms classified under Bacillus subtilis, is an antibiotic commonly used as a topical drug. Bacitracin is synthesized in nature as a non-ribosomal peptide synthetase that can synthesize peptides; however, it is used in the clinic as an antibiotic [2].

Two processes of metabolism:

Our metabolism is complex – put simply it has two parts, which are carefully regulated by the body to make sure they remain in balance. They are:

  • Catabolism – the breakdown of food components (such as carbohydrates, proteins, and dietary fats) into their simpler forms, which can then be used to provide energy and the basic building blocks needed for growth and repair.
  • Anabolism – the part of the metabolism in which our body is built or repaired. Anabolism requires energy that ultimately comes from our food. When we eat more than we need for daily anabolism, the excess nutrients are typically stored in our body as fat.

Metabolic rate:

The body metabolic rate (or total energy expenditure) can be divided into three components, which are:

Basal metabolic rate (BMR) – even at rest, the body needs energy (kilojoules) to keep all its systems functioning correctly (such as breathing, keeping the heart beating to circulate blood, growing and repairing cells, and adjusting hormone levels). The body’s BMR accounts for the largest amount of energy expended daily.

Thermic effect of food (also known as thermogenesis) – our body uses energy to digest the foods and drinks you consume and also absorbs, transports, and stores their nutrients. Thermogenesis accounts for about 5–10 percent of our energy use.

Energy used during physical activity – this is the energy used by physical movement and it varies the most depending on how much energy you use each day. Physical activity includes planned exercise but also includes all incidental activity

Based on a moderately active person this component contributes 20 percent of our daily energy use.

Basal metabolic rate (BMR):

The BMR refers to the amount of energy the body needs to maintain homeostasis. BMR is largely determined by total lean mass, especially muscle mass because lean mass requires a lot of energy to maintain. Anything that reduces lean mass will reduce BMR. As BMR accounts for so much of total energy consumption, it is important to preserve or even increase lean muscle mass through exercise when trying to lose weight.

This means combining exercise with changes towards healthier eating patterns rather than dietary changes alone as eating too few kilojoules encourages the body to slow the metabolism to conserve energy. Maintaining lean muscle mass also helps reduce the chance of injury when training, and exercise increases daily energy expenditure.

An average man has a BMR of around 7,100 kJ per day, while an average woman has a BMR of around 5,900 kJ per day. Energy expenditure is continuous, but the rate varies throughout the day. The rate of energy expenditure is usually lowest in the early morning.

Different Factors affect BMR:

BMR is influenced by multiple factors working in combination, including:

  • Body size: larger adult bodies have more metabolizing tissue and a larger BMR.
  • Amount of lean muscle tissue: muscle burns kilojoules rapidly.
  • Amount of body fat: fat cells are ‘sluggish’ and burn far fewer kilojoules than most other tissues and organs of the body.
  • Crash dieting, starving, or fasting: eating too few kilojoules encourages the body to slow the metabolism to conserve energy. BMR can drop by up to 15 percent and if lean muscle tissue is also lost, this further reduces BMR.
  • Age: metabolism slows with age due to loss of muscle tissue, but also due to hormonal and neurological changes.
  • Growth: infants and children have higher energy demands per unit of body weight due to the energy demands of growth and the extra energy needed to maintain their body temperature.
  • Gender: Generally, men have faster metabolisms because they tend to be larger.
  • Genetic predisposition: our metabolic rate may be partly decided by genes.
  • Hormonal and nervous controls: BMR is controlled by the nervous and hormonal systems. Hormonal imbalances can influence how quickly or slowly the body burns kilojoules.
  • Environmental temperature: if the temperature is very low or very high, the body has to work harder to maintain its normal body temperature, which increases the BMR.
  • Infection or illness: BMR increases because the body has to work harder to build new tissues and create an immune response.
  • Amount of physical activity: hard-working muscles need plenty of energy to burn. Regular exercise increases muscle mass and teaches the body to burn kilojoules at a faster rate, even when at rest.
  • Drugs: like caffeine or nicotine, can increase the BMR.
  • Dietary deficiencies: for example, a diet low in iodine reduces thyroid function and slows the metabolism.

Thermic effect of food:

BMR rises after you eat because you use energy to eat, digest and metabolize the food you have just eaten. The rise occurs soon after you start eating, and peaks two to three hours later. This rise in the BMR can range between two percent and 30 percent, depending on the size of the meal and the types of foods eaten. Different foods raise BMR by differing amounts. For example:

Fats raise the BMR by 0–5 percent.

Carbohydrates raise the BMR 5–10 percent.

Proteins raise the BMR by 20–30 percent.

Hot spicy foods (for example, foods containing chilli, horseradish, and mustard) can have a significant thermic effect.

Energy used during physical activity:

During strenuous or vigorous physical activity, our muscles may burn through as much as 3,000 kJ per hour. The energy expenditure of the muscles makes up only 20 per cent or so of total energy expenditure at rest, but during strenuous exercise, it may increase 50-fold or more.

Energy used during exercise is the only form of energy expenditure that we have any control over. However, estimating the energy spent during exercise is difficult, as the true value for each person will vary based on factors such as their weight, age, health and the intensity with which each activity is performed.

As a rough guide:

  • Moderate exercise means you can talk while you’re exercising, but you can’t sing.
  • Vigorous exercise means you can’t talk and exercise at the same time.

The Host response against metabolism:

The role of the microbiome in influencing the host response is important to how we experience diseases caused by pathogens. Part of the experience of pathogenic diseases like the flu, and Lyme disease is damage caused by the pathogen. Another part of our experience is the host response, like fever and inflammation. The microbiome helps regulate this response.

The interplay between host cells and the microbiome starts before birth when the mother’s microbiome affects the likelihood of a full-term pregnancy. Research on mice raised without a microbiome found that they never develop a mature immune system. The microbes that are with us from our first days are necessary to develop a healthy immune system. Specific metabolites from bacteria have been identified in the regulation of immune cell formation.

Primary metabolites have a key role in the survival of the plant and generally play an active role in respiration and photosynthesis, while secondary metabolites are not involved in the normal growth and development of the plant. Although the absence of secondary metabolites doesn’t cause immediate death, it can lead to the impairment of the survivability of the plant in the long run.

Secondary metabolites are mostly produced by plants for defense purposes. They include alkaloids, steroids, phenolics, resins, essential oils, tannins, flavonoids, lignin, etc. examples of primary metabolites include lipids, carbohydrates, and proteins. In plants, secondary metabolites are limited to an occurrence, and some are restricted to specific taxonomic groups’ species, genera, or families. They are generally accumulated by the plant cells in much smaller quantities than the primary metabolites and are synthesized in specialized cells at different developmental stages. As such, their extraction and purification are often difficult.

Five major human organs are involved in metabolism:

Liver:

If we were a car, and our life would be like an engine. It is vital and essential to keep you running. Over 600 known metabolic functions happen via the liver, and virtually every nutrient, every hormone, and every chemical must be bio-transformed, or made active, by the liver. It’s basically our workhorse.

The liver creates bile, that powerful solution that breaks down fats and the nitrites and nitrates in our meats and bacon. Hormones get secreted from glands all over the body, but it is the liver that breaks down the hormones and makes them biologically active so they can go to work for us. Liver influences electrolyte balance, swelling, dehydration, and water weight. It also acts as a filter for the blood coming through the digestive tract. It converts b-vitamins into co-enzymes and metabolizes nutrients such as proteins, fats, and carbohydrates.

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Guido Putignano
Yealthy
Editor for

Synthetic Biology + Quantum Computing for drug discovery