Martin Eastwood
Nutrition Thoughts
The object of this blog is to extend the information in my text book
PRINCIPLES OF NUTRITION published by BLACKWELL, OXFORD

Dietary fibre has been and continues to be an exciting field to explore.
Looking back however, it was a mistake, possibly a necessary mistake to isolate fibre from the overall field of plant food nutrition. Possibly because clinicians were very active in this field and the medical training emphasises single treatment regimes.
However, fibre is a component of fruit , vegetable, nuts , cereals and legumes in the diet. Not necessarily a vegetarian diet, but plant foods. Plant whole foods are of fundamental import in our diet. Fibre is but one component of that plant food and to neglect the other components, whether this be the proteins, lipids, vitamins, minerals, anti-oxidants and the secondary metabolites is to seriously limit our understanding. Much of the effort on definition and the fibre isolate would have been better used if there had been a whole plant food approach. Whilst an attempt has been made to make life easy for the general public with the proposal of five fruit and vegetables a day, the value of this has been blunted by not indicating which five are the best. Are roots, stalks, seeds, cereals, red, green or yellow , winter, spring or summer grown plants best. There is no sensible logic here based on science. What components of these fruit, vegetables, nuts and legumes are important. My belief is that the identification of important fruit and vegetable components is only just beginning to be made. In the the future secondary metabolites will be seen to be important. When the important and relevant ones are identified, then they should be fitted into a holistic nutritional approach, rather than being heralded, as with fibre as isolates that have assumed unique properties. To make the future even more interesting and complicated coincidental with intensive farming the chemical make up of the the plants may vary . The other unexplored element is individual needs, dependent upon the genetic make up of that person.

GENETICS AND NUTRITION

I have always thought that the genetic make up of an individual is of paramount importance in how that individuaL metabolises their nutrient intake. The isoenzyme structure of an individual and the consequences for metabolism make for infinite permutations, and a unique individual. Which makes nutrition the fascinating science that it can be.

It can be seen how very difficult it is to identify the molecular biological basis of many of the diseases which have been attributed to poor or excessive nutrition. Though the reponse of plants to stress and shortage is a well studied field. It is assumed, possibly correctly that we deal or ather fail to deal with nutrient shortage on a macro or micro scale in a uniform manner. This may not be the case and is worth study.

The establishment of the Human Genome Project is of great importance for the nutritionist whose interest is inter individual variation, interaction with the environment and hence requirements and sensitivities to different nutrients and food ingredients.
As gene identification translates into gene function and the structure of gene products, there is much to be learnt about biochemical pathways and their regulation, which is of great relevance to nutrition. The metabolic process by which each nutrient is converted to energy or to structure and other functions will be individual and dependent upon the efficiency of the isoenzyme complexes in the metabolic pathways. This individual metabolic response will be genetically determined. Major nutrients ( glucose, fatty acids, amino acids ) and minor nutrients ( iron, vitamins ) are involved with hormones in the regulation of gene expression. All nutrients are involved in some manner in the control of gene expression and post translational events.
Variations in the genome structure and resultant protein allosteric variations will dictate the differences in an individual’s ability to metabolise individual nutrients, and this will in part dictate the well being of that individual. The effect of a single gene mutation on an individuals metabolic response to a nutrient may be obvious, though not always so. The effect of such mutations, increased when several genes are involved, may be considerable, in addition to which there are the complicating actions of secondary and tertiary modifiers and other coincidental nutritional factors. All contribute to a complicated interplay between the genome and diet where the impact of inheritance may be low and several dietary factors involved.
The enzyme and isoenzyme differences become important when there is an excess or deficiency of a nutrient when the important differences, and hence vulnerabilities, of individuals will be exposed. Starvation adversely affects individuals regardless of their genetic makeup. What is much more complicated is to understand the response of individuals and different populations to a sufficiency or excess of food. The population eating the food will be of different genetic constitution and the food eaten by different populations will be of differing constitution. Stark examples of populations being exposed to a radically new diet format are provided by the Aborigines of Australia, the Polynesian Islanders and the Native American changing from their accustomed traditional diet to a European type diet. It is recommended by some that we revert to hunter gatherer type diets from 40,000 years ago, yet our alleles may be more in accord with our current diet. The cultural element of taste has also to be taken into the equation.
It is becoming apparent that we the genome can be modieifed in that gens may be turned on and off. It is possible that nutrients , have a role in this on/off process. The likely candidates are amino acids, fatty acid metabolites , trace elements, vitamins and plant secondary metabolites.

Four fifths of known natural products are of plant origin, either primary or secondary metabolites. Plant primary metabolites eg amino acids, sugars, fatty acids, vitamins are involved in plant metabolism , growth , maintenance and survival. The primary metabolites are important in nutrition and metabolism across all the kingdoms.
Plants also contain a group of chemicals called secondary metabolites. These are a group of chemically diverse natural products synthesised and stored only in plants, often peculiar to a few plant species and even parts of the plants, root, shoot , leaf or storage organ. Secondary metabolites are synthesised from a few key intermediates of primary metabolism and include non-protein amino acids, alkaloids, phenols and isoprenoids. Many have no immediately obvious function in cell growth and are produced by cells which have stopped dividing.
Secondary metabolites are regarded as being either toxins or attractants to predators or potential pollinators. They have a role in protection in the struggle with the animal world. They also may have important hormonal and other central roles in the plant in regulating physiological function. The plant hormones or phytohormones is a diverse group of chemicals and includes abscisic acid, auxins, ethylene, cytokinins and gibberllins. It is possible that the function of secondary metabolites also extends across the kingdoms. They have effects on the mammalian central nervous system and cardiovascular system of which plants have no obvious equivalent. Such metabolites include opium, cannabis, digitalis and oubain.
Chemistry
Alkaloids
Alkaloids are a vast family of more than 5000 different chemicals occurring naturally in plants, structurally the most diverse class of secondary metabolites ranging from simple structures such as coniine to the exceedingly complex. The alkaloids are usually classified by the amino acid or derivatives from which they arise. The most important classes are derived from the amino acids ornithine and lysine or from the aromatic amino acids phenylalanine and tyrosine or from tryptophan. Othe alkaloids are derived from anthranilic acid , nicotinic acid , polyketides or terpenoids.
Phenolics
Phenolics are aromatic compounds with hydroxyl substitutions. The parent compound is phenol but most are polyphenolic. In addition to the monomeric and dimeric there are the lignins of plants cell wall, melanin compounds and tannins. These are also substituted phenolic terpenoids eg D1- tetrahydrocannibol. Phenols are classified according to the number of carbon atoms in the basic skeleton. Simple phenols include phenol and catechol (1,2-dihydroxybenzene ). There are derived classes with one, two or three side-chains for example salicylic acid, p-hydroxyphenylacetic acid and hydroxycinnamic acid and caffeic acid.
Flavonoids
Flavonoids are polyphenolic glycosides which occur in edible plants, e.g. citrus fruits, berries, root vegetables, cereals, pulses, tea and coffee. They are hydrolysed by bacteria in the saliva and intestine to quercetin, kaempferol and myricetin.
Isoprenoids
The common denominator in this diverse array of compounds is their universal 5-carbon building block. They are compounds with C5, C10, C15, C20 ….C40 skeletons , monoterpenes, sesquiterpenens and diterpenes. Steroids are a separate catergory. Mevalonic acid a C6 acyclic compound is the precursor of all isoprenoids. Isoprenoids that are classified as primary metabolites include sterols, carotenoids, growth regulators and the polyprenol substitutions of dolichols, quinone and proteins. These compounds are essential for plant membrane integrity, photoprotection, and orchestration of devlopmental programmes.
Metabolic regulation role.
How might these diverse chemicals be relevant to animal metabolism? Earlier in this book in the section on Genetics the concept of shared evolutionary ancestry is mentioned. That is that mammals and plants have conserved genes and proteins which are wholly or partially similar.
Ancient, Conserved Proteins are preserved through evolution either almost intact or in the functional domains of the protein. About 900 ancient conserved regions may account for most of the similarities observed between different phyla. Although eukaryotes as divergent as yeast and humans have a total gene repertoire that differs in size by a factor in excess of 19 , most proteins are likely to be members of only a few thousand gene families.
These proteins are often regulated by secondary metabolites in plants. The secondary metabolites will act in physiological amounts in the plants but are subsequently stored. The secondary metabolites may be stored in seeds and other organs in significantly large amounts, oxalic acid in rhubarb leaves, opium in poppy seed, nicotine in tobacco seed, salicylic acid in willow tree.
The concentration of these metabolites will increase in the plant. When ingested by other creatures, the effect will vary between the physiological, the pharmacological and even the toxic depending upon the amount.
Biological functions may be regulated by coarse and fine control systems. Coarse control requires changes in the regulatory genes which orchestrate transcription, structural genes coding for biosynthetic enzymes, the control of catabolic reactions or the secretion and intracellular targeting of a compound. Fine control involves post translational mechanisms that are on / off switches for biosynthetic processes but which also ensure that the synthetic rate is consistent with the immediate demands of a cell. These include modulation of enzyme activity through protein modification eg protein phosphorylation, feed back regulation through a reaction product or pathway end-product and other kinetic controls which affect the catalytic efficiency of a biosynthetic enzyme. Secondary metabolites in plants can regulate gene and protein function.
Plant secondary metabolites have at least two properties
(1) Type one function where the plant uses the secondary metabolites to interact with other organisms in a protective or attractive manner.
kairomones are members of a heterocyclic group of chemical messengers emitted by organisms of one species which benefit members of another species. These include attractants, phagostimulants and other substances that attract predators to their prey, herbivores to their food plants and parasites to their hosts.
allomone is any chemical substance produced by an organism that when it contacts an individual of another species in nature evokes in the receiver a behavioural or developmental reaction adaptively favourable to the transmitter.
(2) Type two function is where the secondary metabolite acts as a
ectocrine a metabolite that when released from the generating organism, differentially affects other organisms of the same or a different species. Such a metabolite might be harmful to some members of a community and beneficial to others.
The secondary metabolites with type one properties tend to be non-protein amino acids and alkaloids, type two are phenolic and terpenoid families. Type two are probably the family which has nutritional and metabolic benefits to humans.
The systems affected are
1. Genes and protein regulation. Promotors of gene activity include monoterpenes, abscinic acid, methyl jasmonate, flavonoids, gibberillic acid, okadaic acid and 2,4-dichlorphenoxyacetic acid..
2. Mevalonic acid. This is the precursor of the animal and plant sterols of all forms. HMG-CoA reductase is controlled by a number of chemicals including plant secondary metabolites eg brassinosteroids.
3. Transmembrane channel receptors. These can be modulated by a number of chemicals including secondary metabolites eg opiates, cardiac glycosides and abscisic acid.
4. Kinase family of enzymes. The important control enzymes which in turn are controlled by phosphorylation.
5. Cytochrome P450 superfamily. This central haemoprotein enzyme system in the liver has evolved from the same ancestor throughout the kingdoms. Human p450 activity can be altered by plant secondary metabolites.

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