Integrative Healthcare, Functional Medicine & Natural Health!
Metabolism and Metabolic Disorders
– Part One
Question anyone on the concept of metabolism, and you will surely receive responses supporting that everyone knows about it. Young children learn of its existence at school; science students worldwide study the intricate metabolic reactions of living cells, and the general public speaks this technical term during social banter around food and weight. However, metabolism is a facet of human health involving far more than the breakdown of food or the production of energy.
The Five Pillars of Health
Metabolism and the biomedical understanding of metabolic disorders is one of the five pillars of health, supporting the philosophy behind the MINDD Foundation. Over a series of articles, these five pillars will be presented and discussed to help you understand the importance of each for human health, including the biomedical, nutritional and lifestyle measures to improve your own health, your family's health and safeguarding the health of generations to come.
Research and education into the role of Metabolic Disorders in Pediatric health are fundamental to the work of the MINDD Foundation. This two-part article serves to explain the importance of metabolism to our overall state of health, list the conditions associated with errors in metabolism (including the cause of such errors) and what can be done to prevent the potentially devastating consequences of errors of metabolism.
Definition of Metabolism
Metabolism occurs at the cellular and even subcellular level within tiny structures known as organelles. It is usually defined and interpreted in biochemical terms, where all reactions of the metabolic system are considered together. In the most simplistic definition, metabolism is defined as the sum total of all chemical reactions in the body. Metabolism is composed of:
- Anabolism: chemical reactions where substances are synthesised or 'built-up'. For example, the synthesis of hormones, new tissue and antibodies, to name a few.
- Catabolism: chemical reactions where substances are degraded or 'broken down'. For example, the breakdown of food for energy production and the generation of metabolic waste products such as ketones, urea and lactate, to name a few.
Therefore, every single chemical reaction in your body is part of your metabolism. Every useful chemical substance your body makes for you and every waste product generated is part of your metabolism. These metabolic reactions differ depending on which organ of the body you are looking at. For example, the reactions of thyroid metabolism are completely different from reactions in skeletal muscle; every tissue and organ has a completely different role to play and their metabolic chemical reactions reflect this. Your metabolism represents far more than just weight loss and weight gain.
Errors in Metabolism + Causes
Inborn errors of metabolism are a very large group of rare and congenital disorders of metabolism, where babies are born with a genetic defect involving a specific aspect of their metabolism. These conditions are usually inherited. Most are due to single genetic mutations, where the faulty gene leads to the production of a faulty enzyme. The faulty enzyme produced is unable to catalyse its specific chemical reaction in the body (each enzyme in the human body is highly precise and usually only facilitates one specific chemical reaction). The resulting problems are incredibly varied, depending on the gene and enzyme product involved. Some conditions can be managed well, while others can be lethal errors. Depending on the actual condition inherited, symptoms can range from acute and late-onset acute, through to progressive, generalised and permanent symptoms.
List of Conditions
There are hundreds of inherited metabolic disorders, and most are exceedingly rare. As a whole, metabolic disorders usually involve a gene/enzyme product involved in:
- Carbohydrate metabolism: these are usually detected in infancy and cover a vast range of conditions where specific aspects of carbohydrate metabolism are impaired. Energy production in vital organs can be severely compromised. Depending on the exact problem, these conditions are often supported by dietary interventions. Some better-known examples in this category are galactosaemia, lactose intolerance and glycogen storage diseases.
- Amino acid metabolism: these metabolic conditions involve either the synthesis of vital amino acids or impairment of amino acid degradation. These are so many diseases in this category. However, Phenylketonuria (PKU), Homocysteinuria and Maple Syrup Urine disease are some well-known examples. If a vital amino acid is not synthesised, it is unavailable for its many roles within the body. If an amino acid is not degraded correctly, it can build up, causing damage to specific tissues and organs. Dietary interventions are often used to abate the effects of these diseases.
- Organic acid metabolism: these involve the branched-chain amino acids (isoleucine, leucine and valine). If a specific amino acid cannot be broken down, its build-up can lead to academia (dangerously low blood pH) and vital organ damage. Specific dietary interventions are required, and these often commence in infancy.
- Fatty acid metabolism: many enzymes are required to break down fatty acids for energy; a problem with any one of these enzymes is known as an inborn error of lipid (fat) metabolism. Some involve carnitine (which helps transport fatty acids to your mitochondria for energy production), while others prevent correct lipid storage. Yet another vast category.
- Mitochondrial metabolism: these have a huge array of presentations, but ultimately involve impairment of mitochondrial function and ultimately the production of energy as a whole.
- Porphyrin metabolism: porphyrin rings are specific chemical structures found in vital substances such as haeme (predominantly found in red blood cells) and cytochromes (found in mitochondria for energy production and also in hepatic tissue for detoxification). When not synthesised or degraded properly, they are classified as metabolic diseases known as Porphyrias. It is believed that Pyrrole Disorder may belong to this category.
- Purine and pyrimidine metabolism: purines and pyrimidines are essential chemicals produced by the body and contribute to the structure of DNA, RNA and energy molecules such as ATP to name just a few. Defective enzymes governing purine and pyrimidine metabolism affect the normal sequences of human DNA, meaning harmful mutations are common in this group of metabolic diseases.
- Peroxisomal metabolism: peroxisomes are organelles involved in breaking down very-long-chain fatty acids for energy.
- Steroid metabolism: human steroid hormones include oestrogen, progesterone, testosterone, cortisol, and aldosterone. All steroid hormones are derived from cholesterol. Each condition varies, depending on the exact enzyme and hormone involved. Disorders of secondary sexual characteristics, ambiguous genitalia and adrenal insufficiency all come under this category.
- Lysosomal storage diseases. Lysosomes are organelles and can be described as the recycling centre of the cell. Unwanted substances can be converted into useful substances for a cell by lysosomes. Metabolic disorders involving lysosomes result in the accumulation of cellular waste, leading to cellular and organ damage.
Difficulty of Diagnosis
Due to the overwhelming number of metabolic disorders, diagnosis in a clinical setting can be difficult. The range of signs and symptoms that could possibly present is enormous. In general, infants and children who present with the following signs/symptoms may be investigated for congenital metabolic disease, depending on their entire clinical picture and medical case history:
- Failure to thrive
- Growth failure
- Developmental delay
- Delayed or precocious puberty
- Ambiguous genitalia
- Seizures
- Cardiac issues: cardiac failure, myocardial infarction and both high and low blood pressure
- Skin: abnormal pigmentation, lack of pigmentation, excess body hair growth
- Some childhood cancers
- Haematological issues: low platelets, low red cell count, splenomegaly and lymphadenopathy
- Diabetes
- Musculoskeletal pain, weakness and cramping
- Congenital malformations, especially involving facial features
In part 2 of this article: treatment and prevention, and where to seek help for metabolic disorders.
Written by Annalies Corse BMedSc, BHSc
References
Fernandes, John; Saudubray, Jean-Marie; Berghe, Georges van den (2013-03-14). Inborn Metabolic Diseases: Diagnosis and Treatment. Springer Science & Business Media. p. 4. ISBN9783662031476
Jorde, et al. 2006. Carbohydrate metabolism. Medical Genetics. 3rd edition. Chapter 7. Biochemical genetics: Disorders of metabolism. pp139-142
Ogier de Baulny H, Saudubray JM (2002). "Branched-chain organic acidurias". Semin Neonatol. 7 (1): 65–74.
Rosemeyer, Helmut (March 2004). "The Chemodiversity of Purine as a Constituent of Natural Products". Chemistry & Biodiversity 1 (3): 361–401.
Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35.
Vernon, H. (2015). Inborn Errors of Metabolism. Advances in Diagnosis and Therapy. JAMA Pediatrics. 169(8): 778-782
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