Mitochondria: Fuel, Fluxxx and Heat (NSFW)

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Fuel and Fluxxx...

Why do we store fat? Why do we eat?  A scientist who wrote about reproduction, fuel, photoperiods and fecundity wrote the below abstract...[1]

"While there is a relatively direct connection between
circulating levels of metabolic fuels and the GnRH [gonadotropin releasing hormone] pulse generator [in SCN behind the retina], this might not be the only energy-related pathway influencing the secretion of this neuropeptide. The overall control of energy balance is an immensely complex process and a number of pathways involved in it might secondarily influence the activity of GnRH neurons. Peripheral signals influencing energy balance and thus possibly GnRH secretion could come from the liver, pancreas, stomach, duodenum or adipose tissue, and these signals could be sent to the brain via the vagus nerves or by hormones such as leptin, insulin, insulin-like growth factor 1 or ghrelin. These hormones could act directly on the neural circuits controlling the GnRH neurons or they could act by modulating the availability of metabolic fuel. Likewise, the neuropeptides regulating GnRH secretion in the forebrain could also include galanin, orexin, the urocortins and endogenous opioids. Recent interest has focused on kisspeptin, the product of the KISS1 gene. The presence of kisspeptin is necessary for normal reproductive development and it can override the reproductively detrimental effect of mild food restriction."

Obviously how we expend fuel is highly complex and humans are ruled by a big, big, big, hungry, hot brains... Grow or growl? Feast or fast? F-ck or forage? Repair or repast?





HEAT: Cellular Bioenergetics Creates Wildly Explosive, Exothermic Reaction Generating Water



CALORIES IN  ≠  CALORIES OUT

...we are not neat bomb-calorimeters, but open, conserved, networked metabolic and energy systems...

Photos credit: [2].













The Evolution of Body Heat?

When oxidized, the great majority of our food and stored energy goes to the production of HEAT.      What governs this? It is multifactorial but adrenaline, thyroid, cortisol and mitochondria quality are just a few [2]. Active tissues contain more mitochondria. Heat makes us mammals and birds. We have hot bodies, precisely 37C for the great majority.


In the 'Hot Brain:  Survival, Temperature, and the Human Body' the authors theorized that temperature gave us advantages over eukaryotic infections (yeast, fungal origins -- we are eukaryotic) which plagued bird/reptile species which were not armed with high 37C temperatures or fever-inducing capabilities [3].  It is a very interesting theory. Control of thermoregulation (heat loss v. heat gain) is believed to have evolved in the brain of therapsids. Our sinuses are larger. Mammalian brains have a Circle of Willis where 4 arteries (internal carotids and vertebral arteries) provide a complete internal brain circulation with collaterals, such that despite blockage of one or more of the 4 major arteries circulation in the brain and to the body remains intact.  Unfortunately only 25-33% of us have a 'perfect' classic circle of Willis; others have degrees of narrowing or asymetry in certain areas or another. Photos courtesy: Hot Brain, pp. 44, 142.

Recently a microbiologist, Casadevall, from Albert Einstein had the same theory that the rise of mammals can be attributed to 'endothermy and homeothermy [which] are thought to contribute to mammalian resistance to mycosis by creating a thermal exclusionary zone that inhibits most fungal species. The remarkable resistance of mammals to mycotic diseases is probably a combination of a vertebrate immune system, with both innate and adaptive arms, and elevated body temperatures... The currently favored hypothesis for the demise of dinosaurs and end of the age of reptiles is a bolide impact approximately 65 million year ago with the possibility that other events, such as increased volcanism, contributed to disrupting the cretaceous ecosystem. That ecological calamity was accompanied by massive deforestation, an event followed by a fungal bloom, as the earth became a massive compost. Although one cannot know which spores were present at the time, the likelihood that pathogenic fungi existed at the K-T boundary is enhanced by the finding that the potential for pathogenicity probably arose independently several times in evolution...'[3]

'Although we do not know the timeline for the recovery of the planet climate, it is estimated that photosynthesis was shut down for 6 months and climate cooling persisted for at least 9 years, and the occurrence of a fungal bloom sufficient to have left fossil evidence implies that surviving animals were exposed to massive numbers of fungal spores. The darkened skies and cooler temperatures that accompanied the K-T cataclysm would have shielded the sun and reduced the ability of ectothermic creatures such as reptiles to induce fevers by insolation, a necessary activity for protection against fungal diseases. Hence, it is reasonable to posit that ectothermic creatures unable to induce behavioral fevers and in weakened states from environmental stress would have been at a severe disadvantage relative to small mammals with their innate thermal exclusionary zones for fungal growth. Further complicating the situation for reptiles is that eggs can be vulnerable to fungal attack, whereas mammalian progeny would be protected in placentae.'[3]

I think it has merit. We generate a lot of HEAT and it comprises a cr*pload of our total energy losses (as many in NY know without electricity due to Storm Sandy and no heat to fight night time drops to freezing temperatures). As Casadevall reported  'the mammalian lifestyle is energetically costly.'






Mitochondria: Water (H2O) = 286 kJ of P-O-W-E-R

Many obesity researchers appear to forget these multiple evolutionary and hormetic factors in their Big Pharma funded, tenure-track equations. One did not (though partly Joslin funded which is Big Pharma).


In a Nature article, Tseng et al discuss mechanisms to find a drug target to increase cellular bioenergetics and energy expenditure as an anti-obesity strategy [2]. (But... Drug targets are always silly, no?) They discuss PPAR-delta, AMPK and several other pathways with potential promise.  A succinct explanation of how mitochondria produce energy on demand by harnessing the energy from the formation of water in the cellular bioenergetics of mitochondrial metabolism of fuel is provided. They define bioenergetics as the 'Studies the flow of chemical bond energy within organisms. In a living cell, the principal reactions of fuel metabolism take place in the mitochondria, where food energy is released,oxygen is consumed, and water and carbon dioxide are produced.'

All life on earth utilizes the energy formed from water formation to power pathways and metabolism. Remember the Calvin Cycle/Photosynthesis where carbs (glucose) are formed from air (CO2), and energy of the sun? In the mitochondria, the opposite reaction occurs. Energy from the exothermic reaction of water forming from air (O2) and the enzymatic burning of fuel (oxidizable food, glucogen, glucose, fat) result in HEAT and ATP. When one mole of H2O is created from one H2 (hydrogen) and half O2 (oxygen), 286 kJ of power are released (in other words, 68 kcal, which is about one small potato).... FROM FORMATION OF ONLY ONE MOLE OF WATER.

CO2 1/2 O2  =   one mole H2O (~18 grams water = 3.5 teaspoons)  =  286 kJ

Photo Credit: The Art, Mystery and Science of Water

Fuel Efficiency of Our Mitochondrial Cellular Respiration

With cellular respiration, instead of an enormous, exothermic explosion (like a hydrogen bomb), the electrons and protons are added step-wise on a gradient known as the electron transport chain (ECT) in plants and animals.  A biological mitochondrial 'battery' is created with the 'anode' on the inner mitochondrial membrane side and the 'cathode' on the other.  Heat is energy released when oxygen is the final proton acceptor and coupled to the enzyme (F1F0-ATPase) that forms ATP, the universal currency of cellular energy in the body. When the protons fall across the proton channel, ATP is formed.  We use ATP as fuel every minute every day for all cellular work, then recycled back to ADP.  In one day, it is estimated that our mitochondria may produce our own weight in ATP [5].

Efficiency of the theoretical transfer of energy from oxidizable fuel to ATP and heat is pretty darn good: 39% ATP and 61% heat [5]. Mitochondria are energy rockstars. Obviously many biolgical factors determine true efficiency: iron status (cytochromes are composed of heme), ubiquinol, oxidative and inflammatory state, thyroid, HPA axis function, hormones, etc.

Plants (chloroplasts) get 3-6% efficiency from transfer of solar energy to the energy bonds of plant starches and fatty acids. Particular C4 plants can get 7-8% (sugarcane) and one super cyanobacteria strain Chlorobaculum tepidum achieves 10%. Various modern fuel efficiencies are approximately -- for coal (~20-30s%) and solar (20%). Photo credit: [5].



References

1. Climate change and seasonal reproduction in mammals. Bronson FH.Philos Trans R Soc Lond B Biol Sci. 2009 Nov 27;364(1534):3331-40.

2. Cellular bioenergetics as a target for obesity therapy.Tseng YH, Cypess AM, Kahn CR. Nat Rev Drug Discov. 2010 Jun;9(6):465-82. [Free PDF here]

3. The Hot Brain: Survival, Temperature, and the Human BodyCarl V Gisolfi, Francisco Mora Teruel. MIT Press (Bradford Book), 2000. [Free SCRIBD text here]

4. Fungi and the rise of mammals.Casadevall A. PLoS Pathog. 2012 Aug;8(8):e1002808.  [PDF]

5. http://highered.mcgraw-hill.com/sites/dl/free/0073525502/930160/mad25502_ch08.pdf