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Salt hypothesis' story

March 2010

Salt war

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Diabetes vs. drugs, 3:0?

February 2010

The MMR vaccine war: Wakefield vs. ?

Wakefield proceedings: an exception?

Who's afraid of a littl' 1998 study?
 

January 2010

Antibiotic children

Physical activity benefits late-life health

Healthier life for New Year's resolution

 

December 2009

Autism epidemic worsening: CDC report

Rosuvastatin indication broadened

High-protein diet effects

 

November 2009

Folic acid cancer risk

Folic acid studies: message in a bottle?

Sweet, short life on a sugary diet

 

October 2009

Smoking health hazards: no dose-response

C. difficile warning

Asthma risk and waist size in women

 

September 2009

Antioxidants' melanoma risk: 4-fold or none?

Murky waters of vitamin D status

Is vitamin D deficiency hurting you?

 

August 2009

Pill-crushing children

New gut test for children and adults

Unhealthy habits - whistling past the graveyard?

 

July 2009

Asthma solution - between two opposites that don't attract

Light wave therapy - how does it actually work?

Hodgkin's lymphoma in children: better alternatives

 

June 2009

Hodgkin's, kids, and the abuse of power

Efficacy and safety of the conventional treatment for Hodgkin's:
behind the hype

Long-term mortality and morbidity after conventional treatments for pediatric Hodgkin's

 

May 2009

Late health effects of the toxicity of the conventional treatment for Hodgkin's

Daniel's true 5-year chances with the conventional treatment for Hodgkin's

Daniel Hauser Hodgkin's case: child protection or medical oppression?

April 2009

Protection from EMF: you're on your own

EMF pollution battle: same old...

EMF health threat and the politics of status quo
 

March 2009

Electromagnetic danger? No such thing, in our view...

EMF safety standards: are they safe?

Power-frequency field exposure
 

February 2009

Electricity and health

Electromagnetic spectrum: health connection

Is power pollution making you sick?

January 2009

Pneumococcal vaccine for adults useless?

DHA in brain development study - why not boys?

HRT shrinks brains

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YOUR BODY    HEALTH RECIPE    NUTRITION    TOXINS    SYMPTOMS
                                                                                          

Body metabolism

Body metabolism    Cellular metabolism > Sugars > Amino acids > Fatty acids 
Metabolic type

Fatty acid metabolism

Catabolism

Unlike glucose, fatty acids that are burned for energy enter Krebs cycle after so called β-oxidation (due to these chemical reactions clipping off two carbons at the acid end of a fatty acid molecule, with the second carbon atom from that end being β-carbon). In order to undergo β-oxidation, fatty acid has to be

activated by CoA

(the same coenzyme A linking glycolysis to Krebs cycle). This takes place at the outer mitochondrial membrane, where CoA attaches to the alpha carbon of a fatty acid (the first carbon from its acid, or carboxyl group end) via sulfuric bond, replacing the hydroxyl (OH) group of the fatty acid, thus forming a compound called acyl CoA.

After the activation, fatty acid is converted to acylcarnitine and transported to mitochondrial matrix, where it is converted back to acyl CoA and subjected to β-oxidation enzymes located in the matrix.

β-oxidation pathway consists of four chain reactions ending with acetyl CoA molecule forming around alpha and β-carbons of the fatty acid and splitting away from it, while new acid (carboxyl) group forms at the shortened end of acyl CoA, now with two carbons (i.e. two CH2 - dicholomethane - groups) less. Acetyl CoA enters Krebs cycle, in which high-energy electron carriers, NADH and FADH2 are produced, supplying high-energy electrons to the mitochondrial electron transport chain.

Note that the acetyl portion of acetyl CoA is also acyl, with methyl group (CH3) single-bonded to the carboxyl group with its hydroxyl group replaced by CoA, but unlike acyls of fatty acids undergoing β-oxidation, without carbons (i.e. CH2 groups) in between.

Another CoA molecule attaches to the alpha carbon of the shortened acyl CoA, and another two carbon atoms are clipped off as a part of acetyl CoA in the same manner. This cycle repeats until all carbons are clipped off.

So, if "n" is the number of carbon atoms in a fatty acid molecular chain, and it is even,

it takes (n/2)-1 rounds of β-oxidation
to degrade its entire molecule to n/2 acetyl CoA molecules

For fatty acids with odd number of carbon atoms, the number of CoA molecules created equals the needed number of β-oxidation rounds, since the last round leaves behind the 3-carbon propionyl-CoA, which enters Krebs cycle through a different pathway.

This outlines degradation of saturated fatty acids, with single molecular bonds. β-oxidation of unsaturated fatty acids require additional enzymes (desaturases) altering their double bonds.

In addition to n/2 acetyl CoA molecules, each round of β-oxidation generates one molecule of each NADH and FADH2 high-energy electron donors, feeding electron transport chain. So, with the number of carbon atoms in fatty acids commonly ranging from 4 to 24, β-oxidation of an average 14-carbon chain fatty acid, with (14/2)-1=6 rounds, generates six NADH, six FADH2 and 7 acetyl CoA molecules.

With each acetyl-CoA generating three NADH and one of each, FADH2 and GTP during Krebs cycle, the total input of high-energy electron donors for electron transport chain by β-oxidation of this fatty acid is 27 NADH, 13 FADH2 and 7 GTP (guanosine triphosphate, another electron donor produced by Krebs cycle) molecules.

Recalling that these produce 3, 2 and 1 ATP units per molecule entering electron transport chain, respectively, the energy obtained from burning this fatty acid equals 114 ATP units.

Since 2 ATP units are needed for fatty acid activation, the

net energy gain from this fatty acid is 112 ATP molecules.

This compares favorably to 38 ATP units produced from a single glucose molecule. However, this fatty acid molecule is also heavier; per unit of weight, fat produces somewhat more than double the energy obtained from glucose (i.e. carbohydrates in general and, also, protein).
 

Anabolism (Synthesis)

And how do we synthesize fats that we need, including unsaturated fats that partly compensate for the lack of essential fatty acids, and those that accumulate as body fat?

How much of fatty acids are synthesized, and how much burned for energy, is determined by multiple regulatory mechanisms, both hormonal and enzyme-based (allosteric).

Hormones glucagon and epinephrine inhibit fat synthesis, while stimulating (beta) oxidation. To the contrary, insulin stimulates fatty acid synthesis, while inhibiting oxidation. Thus, it is the ratio of insulin vs. these other two hormones that plays significant role in determining the rate of fatty acid synthesis. Obviously, over-consumption of high glycemic index foods, such as sugars and refined complex carbohydrates,

stimulates fat synthesis by elevating cellular insulin levels,

in order to increase glucose uptake by the cells, and lower its blood level.

It also stimulates fat synthesis by elevating acetyl CoA. If it over-saturates Krebs cycle, at the first cycle conversion (oxaloacetate and acetyl CoA to citrate) more citrate will be exported out of mitochondria, to cytosol, via "citrate shuttle", where it feeds synthesis of palmitate (form of palmitic acid, a saturated fatty acid) after reverse conversion to acetyl CoA and, then, to malonyl CoA (the latter requiring biotin as cofactor).

Acetyl CoA conversion to malonyl CoA requires acetyl CoA carboxylase enzyme, which is the limiting factor in fat synthesis. This enzyme is activated by citrate, but inhibited by palmitoyl CoA, the acyl form of palmitate, which is the starting point for synthesis of other (longer) fatty acids, phospholipids for the outer cellular membrane and triacylglycerols - triglyceride form which liver cells (where most of fat synthesis takes place) load onto VLDL (very low-density lipoproteins) for transport to body's adipose tissues.

Thus, as a balancing factor, high cytosolic citrate level, by elevating palmitoyl CoA, indirectly inhibit acetyl CoA carboxylase, which stimulates citrate conversion to oxaloacetate, then malate, and return to mitochondria via malate-pyruvate cycle.

The acetyl CoA carboxylase enzyme itself modulates the rate of fat synthesis by its degree of phosphorylation; its affinity for citrate varies from high to low from unphosphorylated to fully phosphorylated form, respectively.

In addition, as another allosteric feedback mechanism, high palmitoyl CoA level inhibits citrate shuttle and, by that, the process of fat synthesis.

On the other hand, high NADH/ATP level - in other words, high level of cellular energy - inhibit β-oxidation, thus the cellular intake of fat as well, with the excess ending mainly in adipose tissues.

Evidently, there is nothing simple about body's regulation of fat metabolism. The actual mechanism is much more complex than the above brief outline, and a number of factors, both internal and external to the mechanism itself - can influence its final outcome.

Build up of fatty acids from acetyl CoA is accomplished by the large enzyme complex called fatty acid synthase (FAS). Part of it is acyl carrier protein (ACP), needed to activate acetyl CoA - as well as malonyl CoA - by transforming them to acetyl ACP and malonyl ACP. After that, in 4-step reaction analogous to a reverse β-oxidation (which also means it starts at the opposite, methyl end), two carbons at a time, supplied by malonyl CoA, are added to the forming fatty acid chain, until it reaches 16 carbon length - palmitic acid (leaving water and carbon dioxide residue).

Palmitic acid is then converted to its acyl form, palmitoyl CoA, for modification to other fatty acids. This takes place at the cytosolic side of endoplasmic reticulum in liver cells, which have the enzymes necessary for these reactions (fat catabolism takes place in other body cells as well, mainly in the muscles).

The above summary of the cellular fat metabolism, just as those for the other two major macronutrients (proteins and sugars), barely scratches the surface of cellular metabolism. With billions of molecules actively interacting in every cell every single moment, it is the greatest miracle of all that the cell manages to find and preserve that incredibly complex set of reactions maintaining its homeostasis.

All this is taking place within a speck of living tissue smaller than 0.02mm - the size of average human cell. And this microcosm is only one among many trillions of them making up much greater entity, with many complex levels of physiological and functional structure - the human body.

We are still students of its wonder, with much left to learn. But knowing as much - or little - as we know, is enough to draw some logical conclusions with respect to individual metabolism - yours and mine - that do not quite agree with some common perceptions. This is the subject of the following, last article on body metabolism - your metabolic type.

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