Sections II  Definitions – terms used here

Acetyl-CoA (Acetyl coenzyme A):  its main function is to convey carbon atoms within the acetyl group to the Krebs (citric acid) cycle to be oxidized.  It also plays an essential role in the metabolism of glucose, degradation of fatty acids, and the metabolism of amino acids.  It also is one of two components of the common neural transmitter acetylcholine.

Adenosine triphosphate, see ATP

Amino acid:  biologically important organic compounds composed of amine (-NH₂) and carboxylic acid (-COOH)  functional groups, and are essential nutrients. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen.  There are 21 common amino acids, and are the building blocks of proteins and polypeptides. 

Anaerobic process:  one which occurs without the presence of oxygen

Aerobic process:  one which occurs in the presence of oxygen

Apoptosis is a process of programmed, orderly cell death that occurs in multicellular organisms.  Between 50 and 70 billion cells die this way in the average human adult.  Necrosis is unorderly cell death from acute injury.

ATP, Adenosine triphosphate, the body’s energy molecule:   is a nucleoside triphosphate that transports chemical energy created through metabolism in the mitochondria and used to power over 90% of the body’s chemical reactions, such as those which permit muscle contractions and the synthesis of compounds.  ATP goes from a high state of energy to a low state.  The main way ATP goes back to the high state of energy is through absorbing energy from the metabolism of carbohydrates or fats in the mitochondria, where ATP is restored to three phosphate groups (PO4). 

Beta oxidation:   is the catabolic process by which fatty acid molecules are broken down in the mitochondrial matrix of eukaryotes to liberate 2-carbon units, acetyl-CoA, or 3-carbon propionyl-CoA.  They condense with oxaloacetate to form citrate at the "beginning" of the citric acid cycle.

Cancer (neoplasm) a group of cells which have gross mutations in their mitochondria which alters their metabolism, so that they must rely upon by lactic acid fermentation glucose.  Having acquired this abnormal metabolism they attract macrophages, and in a rare fusion occurrence have gained the mitochondrial DNA of a macrophage and thereby have acquired various properties in their nuclear DNA that have been turned on by oncogenes to give that cell and its progeny certain properties of macrophage, which includes the ability to invade adjacent tissues and to colonize certain distant tissues without destruction by the immune system.  Also turned on are the tissue-healing properties (another function of the macrophage): rapid growth, angiogenesis (new blood vessels for the growing cancer, and unlimited reproduction; thus turned off or bypassed are the signals which limit all of those changes and bring about apoptosis.

Carbohydrates (carbs) a biological molecule consisting of a poly-hydrated ketone or aldehyde with carbon, hydrogen, and oxygen and a formula of ­C­n(H₂ O)_n (with a few exceptions); in biochemistry a saccharide.  Common ones are the starches, sugars, and fibers which are starches that resistant to the digestion except for a few insects and some bacteria.  Carbs and fats are the main sources used by the mitochondria and cytosol in the production of ATP and other energy supply molecules.

Citric acid cycle (TCA, Krebs cycle).  The aerobic metabolism of pyruvate (acetyl-CoA) to produce approximately 29 ATP energy molecules—see Krebs cycle for more info.

Cytosol (cytoplasmic matrix):  the water soluble components of cytoplasm, constituting the fluid portion that remains after removal of the organelles and otherintracellular structures.  In this plasma occurs protein biosynthesis, the pentose phosphate pathway, glycolysis (see below) and gluconeogenesis.  Note, the cytoplasm is the cytosol plus the organelles. 

Fatty Acid Metabolism consists of catabolic processes that generate energy (ATP) and anabolic processes that create biologically important molecules (triglycerides, phospholipids, second messengers, local hormones and ketone bodies).  They are the main energy storage form for vertebrates..   Fatty acids (mainly in the form of triglycerides) are therefore the foremost storage form of fuel in most animals, and to a lesser extent in plants. In addition, fatty acids are important components of the phospholipids that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the cell wall, and the membranes that enclose all organelles within the cells, such as the nucleus, the mitochondria, endoplasmic reticulum, and the Golgi apparatus).  Fatty acid oxidation also occurs in peroxisomes when the fatty acid chains are too long to be handled by the mitochondria—greater than 22 carbon and branched chains.. The same enzymes are used in peroxisomes as in the mitochondrial matrix, and acetyl-CoA is generated. The ATP production in the oxidation cycle averages 12 per cycle which starts with acyl-CoA . 

Fermentation (lactic acid fermentation) is an anaerobic (without oxygen) process which turns pyruvate from glycolysis is turned into lactic acid.  The process takes place in the cytosol—not in the mitochondria.

Glucose a monosaccharide is the main energy storage molecule for plants; in animals, it is stored as long chain called glycogen.  Glucose is as one half of the disaccharide sucrose, also obtained by hydrolysis of starches which are long chains of glucose molecules.  Glucose and fat are the main sources for production of ATP.

Glutamine (Q, glutamate) is a nonessential α-amino acid that is used in the biosynthesis of proteins, and has many other functions including a as a necessary intermediate in the Krebs cycle—not a source of ATP, as thought by some.  Cancers can metabolize glutamate to produce ATP, the amount varies, but in general cancer is a glutamate hog.  Thus in starving cancer on a KD diet, there might be sufficient glutamate from proteins to sustain some of the cancer cells.   

Glycolysis from glycose the older term for glucose: is a process in the cytosol or mitochondria in which glucose is broken down into pyruvate in the presence of oxygen (Krebs cycle), or pyruvate to lactic acid (fermentation) in the absence of oxygen.  If anaerobic, glucose is converted to the 3 carbon molecule pyruvate a 10 step enzymatic (fermentation) process that produces 2 ATP molecules from ADP, and also produce NADH (reduced nicotinamide adenine dinucleotide).  Because of the lack of oxygen or damage mitochondria in cancer, the NADH can’t be used in the efficient aerobic Krebs cycle within the mitochondria which produces 29 ATPs.  Cancer because of damaged mitochondria must catabolize glucose to lactic acid, even if oxygen is present.  This anaerobic process occurs in the cytosol to produce only 2  ATP—see fermentation above. 

Ketone bodies are derived from fatty acid.  They aree water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone).   They are produced by during periods of low food intake (fasting, carbohydrate restrictive diets, starvation, sleep, and when not eating for several hours) and prolonged intense exercise,  They are converted into acetyl-CoA which then enters the citric acid cycle (Krebs) and is oxidized aerobically in the mitochondria to produce ATP.  Thus cancer can’t use them.  Unlike free fatty acids, ketone bodies can cross the blood-brain barrier and are therefore available as fuel for the cells of the central nervous system.  They act as a substitute for glucose in the brain.

Ketogenic diet (KD) is a high-fat, adequate-protein, very low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children, dementia, and to starve cancer. With short-term fasting, it is the best diet for obesity.  Because there are low carbs, the mitochondria must metabolize fats.  Carbohydrates are limited to 20 grams per day—some KDs go higher.

Krebs cycle (citric acid cycle): is a series of chemical 10 chemical reactions used to produce ATP through the oxidation of acetyl-CoA derived from carbohydrates, fats, and [insignificantly] proteins. In eukaryotic cells, the Krebs cycle occurs in the matrix of the mitochondrion. (Cancer because of damaged mitochondria can ‘t produce ATP in the mitochondria.)  The last step in this process results in the re-creation of the starting material acetyl-CoA, which is why it is called a cycle.  It is named after Hans Krebs (1937) who had worked in Otto Warburg laboratory--also a Noble Laurette.

Mitochondrion (mitochondria pl.) is a membrane bound organelle found in most eukaryotic cells.  These structures are sometimes described as "the powerhouse of the cell" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy.  A dominate role of the mitochondria is the production of ATP, which is done by oxidizing the major products of glucose, which are pyruvate and NADH, both of which are produced in the cytosol.  The pyruvate is converted to acetyl-CoA for the Krebs cycle. Their number of mitochondria varies, for instance, red blood cells have none, whereas liver cells can have more than 2000., about 1/5^th the volume of a hepatocyte.  Because of the reactive chemical produced in the production of ATP, they are enclosed to prevent seepage of reactive chemical that would damage the cell.  Their DNA is thus subject to much more damage than the DNA in the nucleus of the cells they are found in.  In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling, and cell death, as well as maintaining control of the cell cycle and cell growth.

Mitosis, process of cell division which produces two identical cells from one.

Pyruvate, Pyruvic acid:  it can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through a reaction with acetyl-CoA.^[3] It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation.

Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen which damage cells; includes peroxides, superoxide, hydroxyl radical, and singlet oxygen. Main sources are from the metabolism of glucose in the mitochondria, and from the further degradation of oxidized unsaturated oils in cell walls and from sugars, mainly fructose, that have attached to proteins.  ROS are the main cause for age related chronic conditions associated with the western diet (civilization).

Starch, is a chain or chains of glucose molecules that serve as an energy source for plants, and has varying degrees of digestibility--distinguished from the broader category of carbohydrate which includes other sugars.

Sugar (table sugar, sucrose): 1) a sweet, crystalline disaccharide obtained from the juice of sugar can or sugar beets.  2) In chemistry a class of carbohydrates with 3 or more carbons forming a backbone which to which are attached oxygen  and hydrogen.  Most of these carbon chains can form ring structures with one member of the ring being oxygen. They often form disaccharides that or easily hydrolyzed enzymatically into monosaccharides that usually exist in a ring formation.  3) A generalized name for sweet, short-chain, soluble carbohydrate--consisting of carbon, hydrogen, and oxygen--many of which are used in food.     

Warburg effect & hypothesis Otto Warburg 1924 postulated (Warburg hypothesis):   The key points are (i) insufficient respiration initiates tumorigenesis and ultimately cancer, (ii) energy through glycolysis gradually compensates for insufficient energy through respiration, (iii) cancer cells continue to ferment lactate in the presence of oxygen and (iv) respiratory insufficiency eventually becomes irreversible.

Section III Cancer basics 

All cancers have grossly defective metabolism (limited pathways) because of damage to their DNA in their mitochondria by reactive oxygen species (ROS) generated during metabolism; this is the primary cause.[1]

The damage effect both the appearance under a microscope and its pathways in the production of ATP.

While each cancer is unique, the norm is for their mitochondria to have lost the ability to metabolize glucose, fats, and protein aerobically (with oxygen).  Cancer metabolizes only glucose by anaerobic fermentation—with minor exceptions depending upon mutations and the fusion of mitochondrial DNA (see below).

The oncogenes are transcription factors which switch the cell from aerobic to metabolism without oxygen called fermentation (see Seyfried).  This is a response to the inability of the mitochondria to produce ATP in the Krebs cycle.  Without sufficient ATP the cancer cells—like all cells--will die.

An indolent borderline tumor with an abnormal mitochondria DNA, thus with abnormal metabolism; this defective clump of cells will attract macrophages to aid in the apoptosis of the abnormal (damaged) cells.  If a very rare event occurs in which the DNA of the macrophage’s mitochondria merges with the mDNA in the tumor’s mitochondria, the tumor will gain some of the properties of the macrophage, the deadly ones being to travel and promote healing.  These are the properties of a cancer:  namely to reproduce unlimited times, to grow new blood vessels to nourish the growing cancer, to deactivate signals for program cell death, to spread into adjacent tissue, and for some the ability to colonize in some types of distant tissues (thus not to be detected in tissue by immune cells as being foreign).  This process of mitochondrial DNA fusion converts a benign tumor into a cancer, and possible a deadly one.

 Fusion can occur more than once, thus years later an indolent cancer that has invaded adjacent tissue can become metastatic,

To repeat:  This fusion process changes the tumor in two ways:  1) to acquire properties of the macrophages that permit travel to distant tissues and evade destruction because of being foreign to that tissue; 2) the properties that a macrophage confers to a tissue subsequent to injury, namely to reproduce rapidly and to acquire blood vessels to nourish the newly formed tissue during the repair process.

Like sufficient oxygen to live, a cell must have sufficient ATP to maintain their internal structure, otherwise it quickly dies and undergoes apoptosis (orderly, programmed dismantling).

Because of the abnormal metabolism of cancer, by cutting off the supply of glucose, cancer cells will quickly die, while normal cells will switch to fat metabolism—minor sources of ATP are insufficient. 

Section IV Cancer Metabolism Basics

The mitochondria in cancer cells make ATP by a very inefficient anaerobic fermentation process (without oxygen).  About 1/15^th the amount of ATP is made per glucose molecule compared to the aerobic Krebs cycle.  Thus a cancer cell is a glucose hog; it uses (in part depending on the rate of mitosis) 8 to 200 times the amount of glucose of a normal cell.

Cancer can’t because of damage to their mitochondrial DNA use oxygen, the Krebs cycle is cut off, and thus processes which produce compounds which enter the Krebs cycle, such as from fats and amino acids.  At best these compounds can be utilized in lactic acid fermentation.  Fats are totally cut off and amino acids as building blocks of proteins for cell reproduction. 

Without sufficient ATP cells soon die.  Cancer cells main source of ATP is from formation of glucose (not fats and proteins like normal cells); thus cancer cannot produce sufficient ATP during a fast or probably when on a strict ketogenic diet.  This shortage of ATP will bring about apoptosis to cancer cells[2] while normal cells will switch to fat metabolism via the Krebs cycle (aerobically) in the mitochondria.  

Glutamine and glutamate are hogged by most cancers (NOT secondary sources of ATP for cancer cells, as some claim).  They are used and converted to other compounds that are used for other cellular vital functions including aerobic metabolism.  (The percentages of usage, I need to do a literature research.)  

Fiber and some other resistant carbs are a secondary source of energy, though we can’t digest them.  There are bacteria that can digest these carbs and thus produce glucose.  A modest amount of bacterial-produced glucose is absorbed through the intestine walls (the same too occurs with bacterial produced ethanol as a product of their digestion of glucose--about 2 grams a day are produced). 

The liver will still synthesize some glucose from fats and proteins; however, most of it is used by the liver; erythrocytes (red blood cells) and about 3% of brain cells are dependent on glucose.  The cytosol of cells can produce glucose from protein; however, it too is minimal to sustain a cancer during fasting.

The ketogenic diet might sufficiently starve the cancer, and might not because of the fibers and amino acids on the diet being used to produce ATP.  The same too for energy restricted diet,[3] but not with fasting.

Some cancers might retain some ability to metabolize aerobically glucose or some of the ketones produced in fat metabolism.  It is for this reason that even with prolonged fasting and adherence to the fasting protocol that a small percentage might not be cured. 

Because of damaged mitochondrial DNA that block steps involved in the production of ATP by the aerobic Krebs cycle, oncogenes are turned on so the cell can produce ATP by anaerobic glycolysis in the cytosol  (see appendix 1 for more details)

Having acquired this abnormal metabolism they attract macrophages, and in a rare fusion occurrence have gained the DNA of a macrophage and thereby have acquired turned on various properties in their nuclear DNA that has given that cell and its progeny certain properties of macrophage, which includes the ability to invade adjacent tissues and to colonize certain distant tissues without destruction by the immune system.  They also term on some of the genes that promote tissue healing (a function of macrophages), in particular angiogenesis, and rapid growth.