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Mitochondria

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Mineral Fix notes

Minerals Driving Energy Production

In total, there are up to 22 vitamins and minerals that support mitochondrial enzymes and are needed for energy production. Minerals also help to activate antioxidant enzymes that protect the mitochondria from oxidative stress. Deficiencies in these minerals can lead to a reduction in ATP production, mitochondrial degradation and can accelerate mitochondrial aging.

Importantly, magnesium is needed as a cofactor in several electron transport chain complex subunits, including methylenetetra-hydrofolate dehydrogenase 2 and pyruvate dehydrogenase phosphatase, and controls GLUT4 translocation to the cell membrane surface. GLUT4 is a glucose transporter that helps bring glucose into the cell for energy production. Thus, magnesium deficiency can contribute to a lack of ATP production in the mitochondria. 

The inner mitochondrial membrane contains the electron transport chain (ETC), which is a series of 5 complexes that transfers electrons and protons across the membrane. This drives the creation of ATP by complex V (otherwise known as ATP synthase). Energy containing cofactors like NADH and coenzymes like FADH are used to deliver electrons to the electron transport chain for ATP production.

In the electron transport chain, NAD+ functions as an electron transfer molecule. NAD has two forms: NAD+ and NADH which both govern electron transfer reactions:

  • NAD+ is an oxidizing agent that picks up electrons from other molecules and thus becomes reduced.
  • NADH is a reducing agent that forms from reduced NAD+ and it can then be used to donate electrons to other molecules, thus becoming NAD+ again.

There are 5 membrane-bound complexes in the mitochondrial electron transport chain – complex I, II, III, IV and V. They are all embedded inside the inner mitochondrial membrane. Here is an overview of their role and function:

  • Complex I – In complex I, NADH gets stripped of two electrons that get transported to a lipid-soluble carrier called ubiquinone (Q). Every electron passes through an iron-sulfur cluster. As electrons become oxidized and reduced, an electron current gets formed, which powers the transport of 4 protons per 2 electrons of NADH into the intermembrane space.
  • Complex II – In complex II, additional electrons are delivered to Q by succinate dehydrogenase (SDHA), fatty acids, glycerol 3-phosphate, and other electron donors. Complex II doesn’t carry any protons into the intermembrane space, thus contributing less total energy to the electron transport chain.
  • Complex III – In complex III, electrons are carried to cytochrome c within the intermembrane space through a proton movement system called the Q-cycle. It works by sequential oxidation and reduction of coenzyme Q10 (CoQ10).
  • Complex IV – In complex IV, 4 electrons are removed from the 4 molecules of cytochrome c and transported to molecular oxygen (O 2). This creates 2 water molecules.
  • Complex IV contains copper ions and multiple heme groups.
  • Complex V (ATP synthase) – Complex V is also called ATP synthase because it generates ATP from ADP and inorganic phosphate created by the proton electrochemical gradient. ATP synthase consists of two sub-units FO and F1, which work as a rotational motor. Calcium stimulates ATP synthase.

Carbohydrates, proteins, fatty acids and ketones will ultimately be broken down into acetyl-CoA, which then delivers the acetyl group into the citric acid cycle (TCA or Krebs cycle). Acetyl-CoA created from carbohydrates happens via glycolysis and via beta-oxidation from fatty acids. These pathways require zinc, magnesium and chromium, which ensure the capacity for energy expenditure and muscle performance.

  • Zinc is required to form pyruvic acid from lactic acid – the metabolic product of glucose metabolism.
  • Selenium deficiency causes defects in mitochondrial structure, integrity, and electron transport chain function.
  • Removal of extracellular magnesium ion inhibits glycolysis and limits glucose transport by red blood cells.
  • The availability of zinc, iron and chromium are necessary for the synthesis of insulin and glucose utilization, which contributes to ATP production by the mitochondria.
  • Mitochondrial fat oxidation, which also contributes to ATP production, is initiated by calcium. Calcium is a key regulator of mitochondrial function because it is involved in many mitochondrial enzymes, such as pyruvate dehydrogenase and α-ketoglutarate dehydrogenase as a cofactor.

The entry of acetyl-CoA into the TCA cycle needs magnesium and manganese, which creates NADH and FADH2 to then feed into the electron transport chain (which needs iron and copper) to produce adenosine triphosphate (ATP) the energy currency of cells. All reactions where ATP is involved require magnesium ions. The magnesium ion is an integral part of the last enzyme in the respiratory chain, which initiates reduction of molecular oxygen. As a component of membranes and nucleic acids, magnesium is present in the mitochondria.

  • Magnesium and copper are the star minerals for making ATP and without enough ATP or energy this can lead to fatigue. By binding to ATP and releasing the terminal phosphate, magnesium activates ATP and liberates its energy.
  • A deficiency in magnesium can lead to mitochondrial damage and decreased ATP formation through potassium depletion and sodium and calcium overload. Administrating magnesium can improve symptoms of chronic fatigue and these benefits are associated with increasing low magnesium levels in red blood cells in these patients. Patients treated with magnesium report improved energy levels, better emotional state and less pain. Thus, it might be that people with chronic fatigue or burnout are actually deficient in magnesium or other minerals involved with energy production.

Zinc, selenium, iron, copper, manganese, magnesium and iodine are all needed for proper thyroid functioning.

Magnesium:

  • Essential for nerves and muscle function
  • Co-factor in over 600 enzymatic reactions
  • Required for ATP production and transportation

Calcium:

  • Essential for nerves and muscle function
  • Initiates fat oxidation
  • Carries ATP with magnesium

Phosphorus:

  • Structural component of ATP and creatine phosphate
  • Part of energy metabolism as it makes up ATP

Copper:

  • Involved in iron metabolism and balance
  • Copper is a co-factor for respiratory complex IV in the mitochondria. A copper deficiency impairs immature red blood cell bioenergetics, which alters the metabolic pathways, turning off the mitochondria and switching over to more glycolysis (sugar burning). As a result, there is a reduction in energy production and excessive lactate production from glycolysis. Lactic acidosis or the buildup of lactic acid is associated with several cancers and inflammatory diseases. During oxygen shortage, which can accompany copper deficiency anemia, lactic acid can begin to accumulate.
    • Copper also plays a role in burning fat. Obese patients require more copper than the RDA (typically exceeding 1.23 mg/day). Norepinephrine, the hormone that promotes fat burning and alertness, requires copper for its synthesis. The transcription factor in the hypothalamus called HIF-1 alpha, is also copper-dependent, and it has a role in preventing obesity.

Chromium:

  • Potentiates the actions of insulin and thus glucose uptake
  • Needed for glycolysis and ATP production

Iron:

  • Essential part of hemoglobin for oxygen transport
  • Facilitates transfer of electrons in the respiratory chain
  • Necessary for red blood cell function

Manganese:

  • Co-factor of enzymes involved in carbohydrate metabolism and gluconeogenesis

Zinc:

  • Essential for glycolysis and beta-oxidation
  • Part of over 100 enzymes involved in energy metabolism
  • Needed for producing thyroid hormones

Selenium:

  • Needed for producing thyroid hormones
  • Needed for glutathione and antioxidant production

Iodine:

  • Needed for producing thyroid hormones
  • Affects metabolic rate and energy metabolism

Having enough DHA in the cardiolipin of the mitochondria is extremely important for a cell’s ability to induce apoptosis and controlled cell and/or cancer cell death.

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