Triene/tetraene ratio

Fig. 7. Effect of dietary linoleate upon triene tetraene ratio in total fatty acids of serum lipids of infants.

Fig. 11. Changes in triene tetraene ratio of serum phospholipids in response to fat-free intravenous feeding and intravenous feeding with fat emulsion.

Collins and his colleagues reported the induction of essential fatty acid deficiency in a 44 year old man fed intravenously with a fat-free preparation (Collins et al., 1971). This individual developed erythema and dermatitis and the trieneitetraene ratio of his serum phospholipids increased dramatically over approximately 100 days on fat-free preparation, as is shown in Figure 11. When an intravenous emulsion was fed providing essential fatty acids, the ratio dropped dramatically and when the intravenous emulsions were stopped, the triene tetraene ratio again rose to high levels. A second course of treatment with the intravenous emulsions maintained the triene tetraene ratio for approximately seven weeks. This was the first report of essential fatty acid deficiency in humans caused... 

Press et al., 1974) to be effective in correcting essential fatty acid deficiency in humans. Sufficient oil was absorbed through the skin to reverse the pattern of essential fatty acid deficiency in serum phosphatidyl choline. Their data are plotted in Figure 16. At the end of 12 weeks of cutaneous application of sunflower seed oil, the triene tetraene ratio in serum phosphatidyl choline was in the order of 0.02. The phenomenon has been tested with rats (Bohles et ai., 1976) and found that sufficient oil was absorbed through the skin of rats to reverse the pattern of essential fatty acid deficiency. In our laboratory, an attempt to relieve essential fatty acid deficiency in infants was not successful. Cutaneous application of safflower seed oil at approximately the same dose level used by Press et al. (1974) caused no real change in triene tetraene ratio of serum phospholipids. Press et al. (1974) have e i ressed some doubt that the phenomenon they observed was effective over a longer period of time (private communication). 

Certain biochemical indices are available for determining the presence of either total EFA deficiency or -3 fatty acid deficiency. Linoleic, linolenic and oleic (18 l -9) acids compete for the same desaturation and elongation enzymes that convert these fatty acids to long chain polyunsaturated fatty acids (see Figure 2.3). The desaturases prefer co-3 over -6 over -9 fatty acids (Tinoco et al., 1979). Normally, with sufficient EFA in the diet, tissue levels of eicosatrienoic acid (20 3 -9) are very minor despite the abundance in tissues of its precursor, oleic acid. With total EFA deficiency, tissue levels of eicosatrienoic acid rise concomitant with decreased levels of AA. An increase in this triene/tetraene ratio (20 3 -9/20 4 -6) in blood and tissues is characteristic of total EFA deficiency, but not of -3 fatty acid deficiency (Holman et al., 1964). 

The measurements of the total amount of various essential fatty acids as co-3 fatty acids in plasma, serum, or erythrocyte membrane phospholipids have been indicated as useful markers of essential polyunsaturated fatty adds. Essential fatty acid deficiency is a clinical condition that derives from inadequate status of co-3 and co-6 fatty acids however, the symptoms are nonspecific and may not present prior to marginal essential fatty acid status. Widely used biomarkers for bicx hemi( essai-tial fatty acid deficiency are mead acid and the triene/tetraene ratio. Howcvct, the total plasma triene/tetraene ratio has been considered the gold standard for essential fatty acid deficiency. Mead acid, or 5,8,11-eicosatrienoic acid (5,8,11-20 3 co-9) is synthesized from endogenous oleic acid and is increased when there is insufficient concentrations of linoleic and a-linolenic acid to meet the needs of polyunsaturated fatty acids. Under normal conditions only trace amounts of mead acid are found in plasma. EPA and DHA inhibit mead acid synthesis. Mead acid measurement is an indicator of essential fatty acid deficiency state, while essential fatty add depletion is associated with a decrease in plasma hnoleate and arachidonate percentages. Assessment of long-term essential fatty acid intake is measured in adipose tissue, and it is considered the best indicator because of its slow tumover. - Cutoff values for the assessment of essential fatty adds and to-3 fatty acid status in erythrocytes have been reported. Proposed cutoff values for children older than 0.2 years are 0.46 mol% 20 3 co-9 (mead acid) for early suspicion of essential fatty acid defidency, 0.068 mol/mol docosapentaenoic/arachidonic acid... 

From this discussion it will be apparent that while all EFA are polyunsaturated, not all polyunsaturated fatty acids are EFA. Nutritionists and biochemists have used the ratio of 5,8,11-20 3/5,8,11,14-20 4 (often called the triene tetraene ratio) as a biochemical index of essential fatty acid status (Figure 5.5). For many years, it was held that a ratio greater than 0.4 was diagnostic of EFA deficiency but recent work has suggested that it may be prudent to revise this figure downwards to nearer 0.2. 

Figure 5.5 Influence of dietary linoleic acid on the ratio of 20 3(n-9) to 20 4(n-6) [the triene tetraene ratio ] in different species. The relative scales are similar In all plots the Inset plots are to indicate the similarity in relationship over a wide range of tissues and species. Reproduced with kind permission of Professor R.T. Holman and Pergamon Press Ltd, from Progress in the Chemistry of Fats and Other Lipids (1970), 9, 607-82.

The study of fetal conservation of EFA in ruminants is extremely rewarding since the availability of EFA to the mother is severely limited by rumen hydrogenation (section 3.2.5). The triene/tetraene ratio in fetal lamb tissues is about 1.6, a value that in simple stomached animals would be associated with extensive signs of EFA deficiency. By 10 days after birth, the ratio has fallen to 0.4 and by 30 days to 0.1. These values are well within the normal range despite the extremely low concentration of linoleic acid in ewe s milk (0.5% of energy). Ruminants are, therefore, able to conserve... 

A functional method for detection depends upon competition for the activity of the and desaturases between a non-essential fatty acid (e.g. oleic acid) and an essential fatty acid (see above). If the latter is deficient, oleic acid is readily converted, via the desaturases, to Mead acid, since there is little competition (Figure 11.14). Hence the amount of the latter can be used as a marker for deficiency of essential fatty acids, although it is better to use the ratio of double bonds only three are present in Mead acid (i.e. a triene) but four are present in arachidonic acid (i.e. a tetraene). A ratio in plasma, triene/tetraene >4.0 is an indication of a deficiency of essential fatty acids. This method has shown that a deficiency can occur in a number of conditions which can lead to disease (Table 11.5). 

Essential fatty acid deficiency Deficiency of linoleic acid, linolenic acid, and/or arachidonic acid, characterized by hair loss, thinning of skin, and skin desquamation. Long-chain fatty acids include trienes (containing three double-bonds [e.g., 5,8,11-eicosatrienoic acid, or Mead acid trienoic acids) and tetraenes (containing four doublebonds [e.g., arachidonic acid]). Biochemical evidence of essential fatty acid deficiency includes a trieneitetraene ratio greater than 0.4 and low linoleic or arachidonic acid plasma concentrations. 

With respect to the carbene, arylcyclopropane formation occurs with rather low stereospecificity. In most cases the ewt/o-isomer predominates, which is in accordance with the general observation made when arylmethylenes from other sources are added to alkenes. Thus, photolysis of phenyldiazomethane dissolved in cyclohexene gave 7-phenylbicyclo[4.1.0]heptane (2) in 34% yield with a endojexo ratio of 1.1. Preference for the e (/o-isomer is also observed when monoarylcarbenes are reacted with cyclohepta-l,3,5-triene, but when 1-naphthylcar-bene, 2-naphthylcarbene and 9-anthrylcarbene are reacted with cycloocta-l,3,5,7-tetraene the exo-isomer predominates. ... 

Linoleic acid normally is converted to arachidonic acid (a tetraene fatty acid). If linoleic acid is unavailable, oleic acid will be substituted, which results in production of eicosatrienoic acid (atriene fatty acid) as the metabolic end product. Therefore essential fatty acid deficiency can be detected on the basis of decreased tetraene production and increased triene production. Normally, the ratio of trienes to tetraenes is less than 0.4 when this ratio becomes greater than 0.4, the diagnosis of essential fatty acid deficiency is established. Analysis of plasma fatty acids, however, is expensive and not widely available. 

Treatment of buca-l,3-diene with titaniumfiv) chloride and diethylaluminium chloride gave a mixture of cis,rrans,rran cyclododeca-l,5,9-triene and all-trons-cyclohexadeca-l,5,9,13-tetraene. The co-dimerization of buta-1,3-diene and iso-prene or trons-1-piperylene by nickel acetylacetonate in the presence of triphenyl-phosphite and perhydro-9b-alumophenalene to give 1- or 3-methylcyclo-octa-1,5-diene, has been studied. Buta-1,3-diene has been cyclo-oligomerized in the presence of a nickel catalyst to give a mixture all-rrans-cyclododeca-l,5,9-triene, all trans-cyclohexadeca-1,5,9,13-tetraene and 11-vinyl-all-trans-cyclotetradeca-1,4,8-triene, in the ratio of 80 15 5, respectively, in 90% combined yield. The catalytic... 

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