BioHack Metabolism
BioHack Metabolism
Biohacking is a term used to describe the integration of applied physiology, nutrition, exercise and lifestyle modification in order to manipulate one’s epigenetics to enhance quality of life, health and/or athletic performance. One easy approach to biohacking your metabolism is by following five simple principles based on the acronym S P E E D.
S – SLEEP
In a 2007 research review, Knutson et al. found that chronic partial sleep loss could increase the risk of obesity and diabetes via dysregulation of glucose metabolism (i.e., insulin resistance) and altered neuroendocrine control of appetite. The result was excessive food intake and decreased energy expenditure. The average adult needs between 7.5 and 8 hours of restorative sleep per night. This can vary based on health and additional needs for recovery, such as during periods of intense exercise.
Sleep Loss & Energy Expenditure
Energy expenditure plays an important role in the control of body weight and adiposity. The total amount of daily energy expenditure (TEE) can be divided into three components: Resting metabolic rate (RMR) – The energy expenditure of an individual resting in bed in the morning after sleep in the fasting state. RMR accounts for about 60% of TEE. Thermic effect of food (TEF) – The energy expenditure associated with the digestion, absorption, metabolism, and storage of food. TEF accounts for approximately 10% of TEE. Activity-related energy expenditure (AEE) – The energy expended in exercise as well as activities such as sitting, standing, walking and other occupational, volitional and spontaneous activities, collectively referred to as non-exercise activity thermogenesis (NEAT). Some biohackers advocate using cold-induced thermogenesis as a form of NEAT by taking cold showers or wearing less clothing during daily activities or to bed. A small reduction in ambient temperature, within the range of climate-controlled buildings, is sufficient to increase brown adipose tissue (BAT) activity, which correlates with the cold-induced thermogenesis (CIT) response. The enhancement of cold-induced BAT stimulation may represent a novel environmental strategy in obesity treatment.
Individuals with sleep problems and/or excessive daytime sleepiness report a significant reduction in their levels of physical activity and NEAT, which could reduce AEE. Sleep loss can also affect energy expenditure via its impact on the levels of leptin (a master hormone secreted by adipose tissue that controls hunger and feelings of satiety) and ghrelin (a neuropeptide that stimulates appetite). Leptin can increase energy expenditure, possibly via increased thermogenesis in brown adipose tissue, while ghrelin can decrease locomotor activity such as NEAT.
P – PSYCHOLOGICAL STRESS
Stress adaptation requires a coordinated series of responses mediated through the hypothalamus-pituitary-axis (HPA) and sympathetic nervous system, which act to maintain homeostasis and protect against chronic diseases. Chronic hyperactivation of the HPA axis, which can occur with low calorie dieting, has been linked to visceral fat deposition, insulin resistance, impaired glucose tolerance, altered lipid profiles, and coronary artery disease. Chronic stress can also lead to increased food intake, as well as relapses and overeating after weight loss has been achieved by hypocaloric dieting.
E – ENVIRONMENTAL
There are hundreds of synthetic chemicals currently used for industrial and agricultural applications that are leading to widespread environmental contamination. These include pesticides/herbicides, plasticizers, antimicrobials, and flame retardants. These endocrine-disrupting chemicals (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. In addition, some studies link EDC exposure to obesity, metabolic syndrome, and type 2 diabetes. The Environmental Working Group has a list of the “dirty dozen” endocrine disruptors and an app that identifies these toxic ingredients in cosmetics and other personal-care items. Limiting exposure to EDCs can be done by avoiding chemical laden products and choosing organic when it comes to produce that is highly sprayed and animals that are fed conventional feed.
E – EXERCISE
Muscle and Metabolism
The most effective tool for increasing or maintaining lean body mass (LBM) is resistance training. Resistance training has been shown to limit the loss of LBM during weight loss regimens. Maintaining or increasing LBM is essential for a healthy metabolism. It also reduces the tendency to regain weight and is important for maintaining adequate body function with aging. Resistance exercise has the potential to improve metabolic disorders and reduce the need for medications associated with being overweight (e.g., diabetes and blood pressure). It can also reduce abdominal adiposity and cardiovascular disease risk factors.
EPOC
In the recovery period after exercise, there is an increase in oxygen uptake known as excess post-exercise oxygen consumption (EPOC). The magnitude of EPOC depends on both the duration and intensity of exercise as well as the type (i.e., aerobic or resistance). There is a curvilinear relationship between the magnitude of EPOC and the intensity of the exercise, whereas the relationship between exercise duration and EPOC magnitude appears to be more linear. Training status and sex may also potentially influence the EPOC magnitude. Some of the mechanisms underlying EPOC include replenishment of oxygen stores, adenosine triphosphate/creatine phosphate resynthesis, lactate removal, and increased body temperature, circulation and ventilation. An increased rate of triglyceride/fatty acid cycling and a shift from carbohydrate to fat as substrate source are of importance for the prolonged EPOC component after exhaustive aerobic exercise. A high-intensity, Tabata-style workout is a great way to biohack your metabolism. This approach consists of eight rounds of 20 seconds of intense work, followed by 10 seconds of rest. Excluding warming up and cooling down, a session can be completed in just 4 minutes.
D – DIET
There are a number of ways to biohack your diet to increase your metabolism. Some of these include:
Don’t cut too many calories
When you eat less than you need for basic biological functions (about 1,200 calories), your body adjusts by slowing down your metabolism. In addition, it can elevate cortisol levels, which leads to catabolism of lean body mass and cravings for fat and sugary foods. Low calorie diets also run the risk of micronutrient deficiencies over time.
Take a Matcha
Caffeine is a central nervous system stimulant that can rev up your metabolism. The antioxidant catechin in green tea also provides a boost. Dulloo et al. (1989) found that a single-dose oral administration of 100mg caffeine increased the resting metabolic rate of both lean and obese human volunteers by 3-4% and improved diet-induced thermogenesis. 5 grams of Matcha can provide 68mg of caffeine.
Epic Matcha’s unique combination of nutrients works on several levels to help you lose weight, be healthier, and feel better every day.
1. Matcha Increases Your Metabolism
Your metabolism isn’t set in stone. Many factors can cause your metabolic rate to fluctuate, including aging, muscle mass, hormones, and diet. One group of nutrients that has been proven to increase metabolism are polyphenol catechins, a unique component of a weight loss superfood know as antioxidants that are found in abundance in matcha.
2. Matcha Blocks Fat Cells
Catechins also works with caffeine to inhibit fat cells from forming in your body in the first place. The nutrients in matcha block the ability of your body to break down fats, which then pass through the body instead of becoming part of it. Fat is eliminated instead of being stored.
3. Matcha Protects You Against Free Radicals
Antioxidants are an important part of a healthy diet because they protect your body from damage by free radicals. Free radicals are toxins that cause disease, aging, chronic conditions – and weight gain. Matcha’s high dose of antioxidants helps your body to resist the effects of the toxins. In fact, matcha contains more antioxidants per serving than almost any other food on the planet.
4. Matcha Gives You More Energy
Matcha contains l-theanine, an amino acid that helps your body to process caffeine differently. Matcha provides a more sustained energy boost that lasts 4-6 hours, without any of the crashing or jitters associated with coffee. When you feel more energetic, you’ll be motivated to get active and exercise. You’ll also enjoy the activity more, which makes you more likely to do it again in the future.
5. Matcha Reduces Your Stress
Drinking matcha stimulates the production of alpha waves in your brain, which is a sign of mental relaxation. Studies have proven that L-theanine reduces stress and anxiety by inhibiting cortical neuron excitation. Stress leads to inflammation, which makes you susceptible to weight gain. Matcha’s relaxation-promoting compounds keep you mentally balanced, and less likely to reach for the candy jar.
Don’t forget the fiber
Plant-based diets that are inherently high in fiber can increase fat burning. Colorful vegetables and fruits also have numerous phytonutrients, which can reduce inflammation, resulting in better health and the prevention of many diseases.
Water
A German study found that drinking 500ml of water increased metabolic rate by 30%. The study concluded that drinking 2 liters of water per day would augment energy expenditure and that the thermogenic effect of water should be considered in weight loss programs. I would suggest turning this water into a supercharged drink such as our three treasures tea.
Eat organic foods only
Researchers report that dieters who consume foods with the most organochlorines (chemicals from pesticides which are stored in fat cells) experience a greater than normal dip in metabolism because the toxins interfere with the energy-burning process. Other research hints that pesticides can trigger weight gain. Choose organic in place of highly sprayed foods whenever possible.
Get adequate protein
There are a number of potential beneficial outcomes associated with protein ingestion, some of these include: Increased satiety – Protein generally increases satiety to a greater extent than carbohydrate or fat and may facilitate a reduction in energy consumption. Increased thermogenesis – Higher-protein diets are associated with increased thermogenesis, which also influences satiety and augments energy expenditure. Maintenance or accretion of fat-free mass – In some individuals, a moderately higher protein diet may provide a stimulatory effect on muscle protein anabolism, favoring the retention of lean muscle mass, while improving metabolism. Protein intake of 1.4 – 2.0 g/kg/day for physically active individuals is safe, and may improve adaptations to exercise training.
Eat some bugs.
Scientists took gut microbes from 4 sets of human twins in which one was lean and the other obese, and then introduced the microbes of each twin into different groups of mice and observed weight and metabolic changes in the mouse groups when fed the same diet. Mice populated with microbes from a lean twin stayed slim, whereas those given microbes from an obese twin quickly gained weight. The “lean” and “obese” microbes had different measurable effects on the body’s metabolism. A diet high in fruits and vegetables helps to create a favorable gut biome. Make sure to include prebiotics like sauerkraut and Kim chi.
METABOLISM – THE CORNERSTONE OF ENERGETIC LIFE
Metabolism is the continuous vital process of breaking down organic matter and forming new substances within the tissues of the body. The word is derived from the Greek word metabolemeaning “change.” Indeed, the body is in a constant state of change. The breakdown process is called catabolism whereas anabolism is the process by which living organisms synthesize new molecules. Metabolic reactions are affected by several reaction-accelerating body enzymes (biocatalysts). In addition, metabolism is regulated by hormones, various growth factors, vitamins, minerals, and the autonomic nervous system. Various chemical reactions form so-called metabolic pathways. Energy metabolism in particular is relevant to exercise. Metabolic pathways are crucial for the maintenance of homeostasis (the equilibrium of the body). The long-term imbalance of metabolic pathways may lead to various metabolic disorders. Genetic hereditary enzyme dysfunctions may also cause innate metabolic disorders (for example, a mutation in the MTHFR gene may cause an increased level of homocysteine and therefore an increased risk of cerebrovascular disorders). Examples of metabolism include the breaking down of carbohydrates, proteins and fats into energy (the citric acid cycle), the removal of superfluous ammonia through urine (the urea cycle) and the breakdown and transfer of various chemicals. The metabolic pathway that was first discovered was glycolysis in which glucose is broken down into pyruvate supplying energy (ATP and NADH) to cells.
AEROBIC ENERGY SYSTEM
The aerobic (requiring oxygen) metabolic process is also called cellular respiration. The processes involved in the aerobic energy system (cellular respiration) are glycolysis, pyruvate oxidation, the citric acid cycle and the electron transport chain. In practice, various cascades use glucose and oxygen to produce ATP (adenosine triphosphate) that acts as an energy source. Byproducts of these processes include carbon dioxide and water.
AEROBIC GLYCOLYSIS
The first metabolic phase, glycolysis, takes place in the cytoplasm. When glycolysis occurs under aerobic conditions, a glucose molecule is broken down into pyruvate, simultaneously producing two ATP molecules and two NADH molecules. Glycolysis also takes place under anaerobic conditions; however, the end result in this case is lactate, or lactic acid (see section “Anaerobic energy system”).
CITRIC ACID CYCLE
The citric acid cycle, or Krebs cycle (named after the Nobel prize winner Hans Adolf Krebs who discovered it), takes place in cell mitochondria.74 The primary metabolic compound of the citric acid cycle is acetic acid (acetyl coenzyme A) produced from fatty acids, carbohydrates and proteins. The various reactions of the citric acid cycle (see image) form hydrogen ions and electrons which are then transferred to the inner mitochondrial membrane for oxidative phosphorylation (binding energy to ATP molecules
through oxidation) and the electron transport chain. The reaction releases NADH and small amounts of ATP and carbon dioxide.
The citric acid cycle involves ten steps, each of them affected by B vitamins and certain minerals such as magnesium and iron as well as the liver’s main antioxidant, glutathione. The reactions are inhibited by heavy metals such as mercury, arsenic and aluminum.
Most of the energy generated during the citric acid cycle is captured by the energy-rich NADH molecules. For each acetyl coenzyme A molecule, three NADH molecules are generated and then used for energy in the reaction that follows (oxidative phosphorylation). The regulation of the citric acid cycle is determined by the availability of various amino acids as well as feedback inhibition (for example, if too much NADH is produced, several enzymes of the citric acid cycle are inhibited, slowing down reactions).
Oxaloacetate acts as a compound used to fulfill a sudden need to produce energy (for instance, in the brain or muscles). Taking an oxaloacetate supplement may therefore be useful, and it may even boost the regeneration of mitochondria in the brain, reduce silent inflammation in the body and increase the number of nerve cells. To put it simply, the body incorporates ingenious systems that convert consumed food into electrons which are used as energy for various needs.
OXIDATIVE PHOSPHORYLATION
Oxidative phosphorylation consists of two parts: the electron transport chain and ATP synthase. Oxidative phosphorylation produces most of the energy generated in aerobic conditions (ATP). It is a continuation of the citric acid cycle. In the electron transport chain, hydrogen ions (H+) are released into the mitochondrial intermembrane space. Through ATP synthase, the hydrogen ions released from the intermembrane space move back into the mitochondrion. Using the energy released in the process, ATP synthase converts the ADP used for energy into ATP again. Ubiquinone (coenzyme Q10) acts as a contributor to the electron transport chain. It has been used for decades as a dietary supplement. Low cellular ubiquinone levels may be a predisposing factor for various illnesses due to insufficient aerobic energy production in the cells. In addition, the use of cholesterol medication (statins) has been found to be a contributive factor to ubiquinone deficiency.
BETA-OXIDATION OF FATTY ACIDS
Fatty acids broken down in the digestive system are used for energy in the mitochondria. In this reaction (called beta-oxidation), the fatty acids are activated by being bound to coenzyme A. The result is acetyl coenzyme A (see above) which is used for energy production in the citric acid cycle. The oxidation of long-chain fatty acids requires carnitine acyl transferases in which the fatty acids are transported from the cytoplasm into the mitochondrion. Such transfer of short- and medium-chain fatty acids into mitochondria is unnecessary as they move there by diffusion.
ANAEROBIC ENERGY SYSTEM
The term “anaerobic” refers to reactions that happen without oxygen present. The anaerobic energy system is needed in circumstances in which oxygen is not immediately available in the quantities required, for example during high-intensity sports activity. In the anaerobic energy system, ATP is produced by breaking down glucose polymers (glycogens) stored in muscles and the liver as well as by utilizing the free ATP molecules immediately available in the muscle cells.
ANAEROBIC GLYCOLYSIS
During anaerobic glycolysis, glucose is broken down into pyruvate which is then converted into lactic acid (lactate) during the lactic acid fermentation process. The lactic acid fermentation takes place when oxygen is not available for energy production.
CREATINE PHOSPHATE SYSTEM
The creatine phosphate system is one of the main energy sources for muscles. It is estimated that approximately 95 % of the body’s creatine is located in the skeletal muscles. Creatine phosphate (phosphocreatine) is synthesized in the liver from creatine and phosphate (from ATP; see above). Red meat is a source of creatine, and it can also be synthesized from amino acids (arginine and glysine). Creatine is used as a dietary supplement (creatine monohydrate) as it significantly increases force generation in the skeletal muscles. Creatine is formed and recycled in the creatine phosphate shuttle (see image). The shuttle transports high-energy ATP molecule phosphate groups from mitochondria to myofibrils (muscle fibers), forming phosphocreatine (creatine phosphate) through creatine kinase. It is used by the muscles for fast energy production. Unused creatine is transported by the same shuttle into mitochondria where it is synthesized into creatine phosphate. Used phosphocreatine forms creatinine which exits the body in urine via the kidneys.
When determining the filtering capability of the kidneys, it is useful to measure the blood creatinine level. The higher a person’s muscle mass, the higher the volume of creatinine secreted. Because of this, the muscle creatine level and blood creatinine level of men are usually higher than those of women.
THE BODY’S MAIN ENERGY STORAGE SYSTEMS
The body utilizes two different types of energy storage. Energy-dense molecules such as glycogen (sugar) and triglycerides (fat) are stored in the liver, muscles and adipose tissue (fat; triglycerides only). Another important type of energy storage is comprised of the electrochemical ions located between cell membranes. Due to its complex nature, the latter is not covered here.
GLYCOGEN
Glycogen is a large-size molecule formed of several (up to 30,000) glucose molecules. Glycogen is stored in the liver (10 % of the weight), muscle cells (2 % of the weight) and, to a lesser extent, red blood cells. In addition to glucose, glycogen binds triple the amount of water. Because of this, a person’s body weight may fluctuate by several kilograms within a 24-hour period depending on the fill level of the glycogen reserves. The glycogen storage in the liver acts as an energy reserve for the entire body’s energy production needs, and those of the central nervous system in particular. The glycogen storage in the muscles is only used for the energy production of muscle cells. The amount of glycogen present is determined by physical exercise, the basal metabolic rate and eating habits.
The glycogen reserves are especially important for the regulation of blood sugar between meals and during intensive exercise. Glucose may also be used for energy under anaerobic conditions. Conversely, fatty acids are broken down into energy only under aerobic conditions. The brain needs a steady level of glucose although it is able to utilize, for example, the ketone bodies produced by the liver during fasting. A metabolically active glycogen breakdown product is glucose 6-phosphate in which the glucose molecule binds with one phosphate group. It may be used for energy in a muscle under either aerobic or anaerobic conditions, utilized via the liver as glucose elsewhere in the body or converted into ribose and NADPH for use in various tissues (for example in the adrenal gland, red blood cells, mammary glands and the fat cells in the liver).
ADIPOSE TISSUE
Adipose tissue (fat) is the body’s main long-term energy storage system. In addition to fat cells (adipocytes), it consists of connective tissue cells and vascular endothelial cells. Fat cells contain a lipid droplet consisting of triglycerides and glycerol. Adipose tissue is located under the skin (subcutaneous adipose tissue), in bone marrow, between muscles, around internal organs (visceral fat) and in the breast tissue. Visceral fat is particularly detrimental to health as it increases the risk of type 2 diabetes, coronary heart disease and various inflammatory diseases. Adipose tissue is also a hormonally active (endocrine) organ. Adipose tissue produces for example, leptin, adiponectin and resistin that regulate the energy metabolism and body weight. Adipose tissue is ever changing, storing or breaking down free fatty acids for use by the body. The process of breaking down adipose tissue into energy is called lipolysis. In lipolysis, triglycerides of the adipose tissue are oxidized by lipase and triglyceride lipase into free fatty acids and glycerol. Fatty acids are used for energy in the muscles, liver and heart; glycerol is mainly used in the liver.
Conversely, insulin inhibits lipolysis. If the body’s stored insulin levels are consistently elevated, the fatty acids circulating in the blood are stored in the adipose tissue. This is called lipogenesis. In particular, the secretion of insulin is stimulated by high blood sugar levels and a carbohydrate-rich diet. An abundant protein intake also increases insulin secretion.
Mitochondria
Mitochondria are often referred to as the powerhouses of the cell. They help turn the energy we take from food into energy that the cell can use. But, there is more to mitochondria than energy production. Present in nearly all types of human cell, mitochondria are vital to our survival. They generate the majority of our adenosine triphosphate (ATP), the energy currency of the cell. Mitochondria are also involved in other tasks, such as signaling between cells and cell death, otherwise known as apoptosis.
The structure of mitochondria
Mitochondria are small, often between 0.75 and 3 micrometers and are not visible under the microscope unless they are stained. Unlike other organelles (miniature organs within the cell), they have two membranes, an outer one and an inner one. Each membrane has different functions. Mitochondria are split into different compartments or regions, each of which carries out distinct roles.
Some of the major regions include the:
Outer membrane: Small molecules can pass freely through the outer membrane. This outer portion includes proteins called porins, which form channels that allow proteins to cross. The outer membrane also hosts a number of enzymes with a wide variety of functions.
Intermembrane space: This is the area between the inner and outer membranes.
Inner membrane: This membrane holds proteins that have several roles. Because there are no porins in the inner membrane, it is impermeable to most molecules. Molecules can only cross the inner membrane in special membrane transporters. The inner membrane is where most ATP is created.
Cristae: These are the folds of the inner membrane. They increase the surface area of the membrane, therefore increasing the space available for chemical reactions.
Matrix: This is the space within the inner membrane. Containing hundreds of enzymes, it is important in the production of ATP. Mitochondrial DNA is housed here (see below).
Different cell types have different numbers of mitochondria. For instance, mature red blood cells have none at all, whereas liver cells can have more than 2,000. Cells with a high demand for energy tend to have greater numbers of mitochondria. Around 40 percent of the cytoplasm in heart muscle cells is taken up by mitochondria. Although mitochondria are often drawn as oval-shaped organelles, they are constantly dividing (fission) and bonding together (fusion). So, in reality, these organelles are linked together in ever-changing networks. Also, in sperm cells, the mitochondria are spiraled in the midpiece and provide energy for tail motion.
Mitochondrial DNA
Although most of our DNA is kept in the nucleus of each cell, mitochondria have their own set of DNA. Interestingly, mitochondrial DNA (mtDNA) is more similar to bacterial DNA. The mtDNA holds the instructions for a number of proteins and other cellular support equipment across 37 genes. The human genome stored in the nuclei of our cells contains around 3.3 billion base pairs, whereas mtDNA consists of less than 17,000. During reproduction, half of a child’s DNA comes from their father and half from their mother. However, the child always receives their mtDNA from their mother. Because of this, mtDNA has proven very useful for tracing genetic lines. For instance, mtDNA analyses have concluded that humans may have originated in Africa relatively recently, around 200,000 years ago, descended from a common ancestor, known as mitochondrial Eve.
What do mitochondria do?
Mitochondria are important in a number of processes. Although the best-known role of mitochondria is energy production, they carry out other important tasks as well. In fact, only about 3 percent of the genes needed to make a mitochondrion go into its energy production equipment. The vast majority are involved in other jobs that are specific to the cell type where they are found. Below, we cover a few of the roles of the mitochondria:
Producing energy
ATP, a complex organic chemical found in all forms of life, is often referred to as the molecular unit of currency because it powers metabolic processes. Most ATP is produced in mitochondria through a series of reactions, known as the citric acid cycle or the Krebs cycle. Energy production mostly takes place on the folds or cristae of the inner membrane. Mitochondria convert chemical energy from the food we eat into an energy form that the cell can use. This process is called oxidative phosphorylation. The Krebs cycle produces a chemical called NADH. NADH is used by enzymes embedded in the cristae to produce ATP. In molecules of ATP, energy is stored in the form of chemical bonds. When these chemical bonds are broken, the energy can be used.
Cell death
Cell death, also called apoptosis, is an essential part of life. As cells become old or broken, they are cleared away and destroyed. Mitochondria help decide which cells are destroyed. Mitochondria release cytochrome C, which activates caspase, one of the chief enzymes involved in destroying cells during apoptosis. Because certain diseases, such as cancer, involve a breakdown in normal apoptosis, mitochondria are thought to play a role in the disease.
Storing calcium
Calcium is vital for a number of cellular processes. For instance, releasing calcium back into a cell can initiate the release of a neurotransmitter from a nerve cell or hormones from endocrine cells. Calcium is also necessary for muscle function, fertilization, and blood clotting, among other things. Because calcium is so critical, the cell regulates it tightly. Mitochondria play a part in this by quickly absorbing calcium ions and holding them until they are needed. Other roles for calcium in the cell include regulating cellular metabolism, steroid synthesis, and hormone signaling.
Heat production
When we are cold, we shiver to keep warm. But the body can also generate heat in other ways, one of which is by using a tissue called brown fat. During a process called proton leak, mitochondria can generate heat. This is known as non-shivering thermogenesis. Brown fat is found at its highest levels in babies, when we are more susceptible to cold, and slowly levels reduce as we age.
Mitochondrial disease
If mitochondria do not function correctly, it can cause a range of medical problems. The DNA within mitochondria is more susceptible to damage than the rest of the genome. This is because free radicals, which can cause damage to DNA, are produced during ATP synthesis. Also, mitochondria lack the same protective mechanisms found in the nucleus of the cell. However, the majority of mitochondrial diseases are due to mutations in nuclear DNA that affect products that end up in the mitochondria. These mutations can either be inherited or spontaneous. When mitochondria stop functioning, the cell they are in is starved of energy. So, depending on the type of cell, symptoms can vary widely. As a general rule, cells that need the largest amounts of energy, such as heart muscle cells and nerves, are affected the most by faulty mitochondria. The following passage comes from the United Mitochondrial Disease Foundation:
“Because mitochondria perform so many different functions in different tissues, there are literally hundreds of different mitochondrial diseases. […] Because of the complex interplay between the hundreds of genes and cells that must cooperate to keep our metabolic machinery running smoothly, it is a hallmark of mitochondrial diseases that identical mtDNA mutations may not produce identical diseases.”
Diseases that generate different symptoms but are due to the same mutation are referred to as genocopies. Conversely, diseases that have the same symptoms but are caused by mutations in different genes are called phenocopies. An example of a phenocopy is Leigh syndrome, which can be caused by several different mutations. Although symptoms of a mitochondrial disease vary greatly, they might include: loss of muscle coordination and weakness, problems with vision or hearing
learning disabilities, heart, liver, or kidney disease, gastrointestinal problems, neurological problems, including dementia, Other conditions that are thought to involve some level of mitochondrial dysfunction, include: Parkinson’s disease, Alzheimer’s disease, bipolar disorder, schizophrenia
chronic fatigue syndrome, Huntington’s disease, diabetes & autism.
Cellular Respiration: Glycolysis, Krebs Cycle, Electron Transport Chain
Atp Production & Kreps Cycle Summary:
The Krebs cycle uses the two molecules of pyruvic acid formed in glycolysis and yields high-energy molecules of NADH and flavin adenine dinucleotide (FADH2), as well as some ATP. The Krebs cycle occurs in the mitochondrion of a cell.
The citric acid cycle (CAC) – also known as the TCA cycle (tricarboxylic acid cycle) or the Krebs cycle– is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins, into adenosine triphosphate (ATP) and carbon dioxide. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically.[3][4] Even though it is branded as a ‘cycle’, it is not necessary for metabolites to follow only one specific route; at least three segments of the citric acid cycle have been recognized.
The name of this metabolic pathway is derived from the citric acid (a type of tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD+ to NADH, and produces carbon dioxide as a waste byproduct. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP.
In eukaryotic cells, the citric acid cycle occurs in the matrix of the mitochondrion. In prokaryotic cells, such as bacteria, which lack mitochondria, the citric acid cycle reaction sequence is performed in the cytosol with the proton gradient for ATP production being across the cell’s surface (plasma membrane) rather than the inner membrane of the mitochondrion. The overall yield of energy-containing compounds from the TCA cycle is three NADH, one FADH2, and one GTP.
Although cancer has historically been viewed as a disorder of proliferation, recent evidence has suggested that it should also be considered a metabolic disease. Growing tumors rewire their metabolic programs to meet and even exceed the bioenergetic and biosynthetic demands of continuous cell growth. The metabolic profile observed in cancer cells often includes increased consumption of glucose and glutamine, increased glycolysis, changes in the use of metabolic enzyme isoforms, and increased secretion of lactate. Oncogenes and tumor suppressors have been discovered to have roles in cancer-associated changes in metabolism as well. The metabolic profile of tumor cells has been suggested to reflect the rapid proliferative rate. Cancer-associated metabolic changes may also reveal the importance of protection against reactive oxygen species or a role for secreted lactate in the tumor microenvironment.
Discoveries of Otto Warburg
Otto Warburg’s pioneering work in the 1920s established that tumor cells exhibit altered metabolism. Warburg discovered an important distinction between the relative use of different modes of energy production in normal cells and tumors. In normal tissues, most of the pyruvate formed from glycolysis enters the tricarboxylic acid (TCA) cycle and is oxidized via oxidative phosphorylation. In tumors, in contrast, the pyruvate is largely converted to lactic acid and energy is produced anaerobically. This finding seemed counterintuitive. Surely, a rapidly proliferating cancer cell would prefer the 36 ATPs that can be claimed by complete oxidation of a glucose molecule to the two ATPs available through glycolysis. Furthermore, this shift in metabolism in which pyruvate is converted to lactate and secreted, rather than being oxidized, occurred in tumors even when there was sufficient oxygen to support mitochondrial function. The conversion of most pyruvate to lactate through fermentation, even when oxygen is present, is called aerobic glycolysis or the Warburg effect.
