Tangled metabolic pathways.

Metabolic pathways are the succession of chemical changes which convert one compound into another within the body. There are many: the entire number is probably not known and there are even more subsidiary and partial pathways by which biochemical processes proceed.  The pathways themselves are highly complex and depend upon routing through enzymes, co-enzymes as well accelerating and retarding factors. These routes change with different ingestants and external factors, even unlikely factors such as sunlight, in their complexity as a manufactory.

That these pathways can “learn” to take increased loads and can be trained to be more efficient and act more rapidly can be demonstrated in enhanced metabolism (“adaption”) of drugs and alcohol. Mitochondria engineer these intra-cellular modifications. This “training” might be the basis of athletic fitness (other factors such as muscle hypertrophy and muscle memory training are clearly also involved)

At simplest these pathways allow the assembly of those carbon based substances which form biological structures and allow degradation of material in order to provide energy. Disassembly of “organic” components to be reused in growth, repair, adaptation and excretion of “waste” is further role.

These biochemical pathways can be compared with complex railroad transit systems having junctions, points, lay-bys, regular sites of loading and unloading as well as the ability to regulate the load carried.

Many disease processes can be attributed to aberrations or failures of these metabolic “transport systems”.  Many diseases probably occur as a result of unknown happenings in these biochemical pathways.

Therefore, if one considers nutrition, one must consider these pathways, by which ingestants are disassembled, transported through (usually) the intestinal boundaries.  In themselves, these intestinal transits are highly complex, selective and prone to disease or abnormality.

21st century humans ingest in very different fashions from their evolutionary predecessors.  Ingestants have changed and have become complex by a variety of manufacturing and industrial events.  What then is the likelihood that the biochemical pathways have become altered, “confused” or overloaded beyond design specification?  This would seem not only highly likely but to be accepted and guaranteed.

Therefore, let us look at the common ingestants, the basic feedstock of humans, and the source of their fuel-energy dynamics.  Preeminent is carbohydrate.   For practical purposes all carbohydrate is grown as vegetation.  ( some sugars, exemplified by lactose, have animal origins) So important is food to human behaviour and existence that the wealthiest nations have, as their economic foundation, successful agriculture.

The vegetative production of carbohydrate has been substantially altered over the centuries.  In broad terms, carbohydrate is not palatable and not an attractive ingestant but it has been altered to be more enticing, primarily by increasing the sugar.  The fruit which we eat now has been selectively bred and is considerably sweeter than the fruit provided to primitive man (as a generalisation).  Even substances like corn have been made softer, sweeter and probably fattier by selective breeding.  More recently the changes of selective breeding have been accelerated by genetic engineering, but the perspective must be retained that genetic engineering has had less influence on palatability than selective breeding.  Much of genetic engineering relates to enhanced production efficiency with greater yields and resistance to adverse events such as drought and disease.  Shelf life has been improved and methods of removing contaminants (including contaminating infections and their by-products such as the flavo-proteins) have been forcibly and successfully addressed.

Probably the single most influential change has been the enhanced production of sugars.  Not only has the feedstock been made sweeter but the sugars themselves have been produced in enormous quantities as a standalones or additives.

One result  of the “industrialisation” of food is that carbohydrate has been changed from the highly fibrous and cellulose wrapped (and therefore relatively unpalatable). Carbohydrate is now an easily accessed and addictively attractive substance with a long shelf life, made immediately available to millions of households. Because it does not deteriorate (assisted by long-life additives) it can be snacked at will, on impulse, as a consolation or a habit from the readily available stock in most hoseholds.

Other attracting and seductive foods have been mixed with carbohydrate to make carbohydrate relatively inexpensive and highly, if not addictively, desirable. Eminent are salt and fat.  Carbohydrate has been introduced into the diet of infants and children in this way and so probably changing their taste and purchase preferences forever.  One has only to look at breakfast cereals where the bulk is cheap carbohydrate but “flavoured” (and for the word flavour think behaviour changing) with the two most powerful enticers, fat and sugar.

Of concern also is the industrial removal of substances from food, such as “de-bittering”. That bitterness, nature’s negative attractant is caused by a variety of substances such as tannins. These would “normally” have the effect of binding molecules and making some foods non-digestible. Removing them will increase absorbable calories, and reduce colon bulk. There is evidence that some of these lost “bitter” components could prevent cancers.

Atheroma demonstrates an analogy with gout. The “pathological substance” of atheroma is cholesterol. This is a normal constituent of the biology of humans. Cholesterol plays a vital part in the structure of the neurological system, and much more. To suggest that cholesterol can be removed from human metabolism (by reducing intake) is ludicrous. What needs to be corrected is the deposition in arterial walls. Now look at gout where the pathological substance is uric acid – a perfectly normal constituent of human metabolism. In humans uric acid is converted, by a metabolic pathway, to urea. Urea is soluble and readily excreted in urine. However if the metabolic pathway is disrupted, uric acid accumulates and disease (gout) results. This metabolic pathway disruption can be caused by genetic factors, overload by ingestion, and other physical factors. Not unlike atheroma.

The physical factor in atheroma is reflected by vascular damage by high pressures of blood, areas of blood turbulence and perhaps loss of blood vessel wall elasticity. Yet another factor might be direct damage to the arterial wall by tiny shards of metal generated in the opening of metal cans. This might explain the high incidence of atheroma in young GIs in Viet Nam: They lived on canned food, probably injesting these metal shards which might be expected to damage arterial walls, especially in areas of is high turbulence of the blood.

Could excessive food volume alone confuse the metabolic pathways and produce disease? Could mixing different types of food taken at the same meal confuse the metabolic pathways and produce disease?


What about dieting? The analogy with the law of physics, “matter cannot be created or destroyed”, has lead to a dieting illusion. It is often held that losing weight can be worked on the basis “calories in = calories out (by exercise)”. Hence calorie counting. But that can be shown that is invalid as a way of reducing fat. More likely exercise (which undoubtedly can lead to loss of weight, particularly fat loss) changes the metabolic pathways (perhaps from glucose catabolism to fat catabolism), allowing selective burn of fat.


About jp

Orthopaedic Surgeon
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