Ruminants fatty acid synthesis

Acetyl-CoA, formed from pyruvate by the action of pyruvate dehydrogenase, is the major building block for long-chain fatty acid synthesis in nonruminants. (In ruminants, acetyl-CoA is derived directly from acetate.)... 

In all species, the principal precursor for fatty acid synthesis is acetyl CoA, derived in non-ruminants from glucose and in ruminants from acetate or oxidation of /1-hydroxybutyrate. Acetyl CoA is first converted, in the cytoplasm, to malonyl CoA ... 

In non-ruminants, the malonyl CoA is combined with an acyl carrier protein (ACP) which is part of a six-enzyme complex (molecular weight c. 500 kDa) located in the cytoplasm. All subsequent steps in fatty acid synthesis occur attached to this complex through a series of steps and repeated cycles, the fatty acid is elongated by two carbon units per cycle (Figure 3.8, see also Lehninger, Nelson and Cox, 1993). 

In ruminants, / -hydroxybutyrate is the preferred chain initiator (labelled / -hydroxybutyrate appears as the terminal four carbons of short- to medium-chain acids), i.e. the first cycle in fatty acid synthesis commences at /J-hydroxybutyryl-S-ACP. 

In the ruminant mammary tissue, it appears that acetate and /3-hydroxybutyrate contribute almost equally as primers for fatty acid synthesis (Palmquist et al. 1969 Smith and McCarthy 1969 Luick and Kameoka 1966). In nonruminant mammary tissue there is a preference for butyryl-CoA over acetyl-CoA as a primer. This preference increases with the length of the fatty acid being synthesized (Lin and Kumar 1972 Smith and Abraham 1971). The primary source of carbons for elongation is malonyl-CoA synthesized from acetate. The acetate is derived from blood acetate or from catabolism of glucose and is activated to acetyl-CoA by the action of acetyl-CoA synthetase and then converted to malonyl-CoA via the action of acetyl-CoA carboxylase (Moore and Christie, 1978). Acetyl-CoA carboxylase requires biotin to function. While this pathway is the primary source of carbons for synthesis of fatty acids, there also appears to be a nonbiotin pathway for synthesis of fatty acids C4, C6, and C8 in ruminant mammary-tissue (Kumar et al. 1965 McCarthy and Smith 1972). This nonmalonyl pathway for short chain fatty acid synthesis may be a reversal of the /3-oxidation pathway (Lin and Kumar 1972). 

Knudsen and Grunnet (1982) have proposed an interesting system for the control of medium-chain fatty acid synthesis by ruminant mammary tissue. Their proposal is based on their observations that ruminant mammary tissue fatty acid-synthetase exhibits both medium-chain thioesterase (Grunnet and Knudsen 1978) and transacylase (Knudsen and Grunnet 1980) activity and that medium-chain fatty acids synthesized de novo can be incorporated into TG without an intermediate activation step (Grunnet and Knudsen 1981). They proposed that the synthesis of the medium-chain fatty acids is controlled by their incorporation into TG (Grunnet and Knudsen 1981). Further work will be needed to substantiate transacylation as a chain-termination mechanism in fatty acid synthesis by ruminant mammary tissue. 

Very little data are available regarding effects of anabolic steroid implants on the lipid metabolism in growing ruminants. Lipogenic enzyme activity and fatty acid synthesis in vitro were elevated in subcutaneous adipose tissue from bulls implanted with estradiol (44), which may account for the increase in fat content of carcasses reported in some studies. TBA implants have no effect on lipogenesis in intact heifers, and only tend to reduce lipogenic enzyme activities in ovariectomized heifers (45). 

The basic starting substrate for fatty acid synthesis is acetyl-CoA (see below). In ruminants, the provision of this substrate is straightfoward. Acetate from blood (+ CoA + ATP) is converted by the cytosolic acetyl-CoA synthase (EC 2.3.1.169) to AMP and acetyl-CoA, which can then be used for fatty acid synthesis. In non-ruminants, glucose is converted via the glycolytic pathway to pyruvate, which is, in turn, converted to acetyl-CoA in mitochondria. Acetyl-CoA thus formed is converted to citrate which passes out to the cytosol where it is cleaved by ATP-citrate lyase (EC 2.3.3.8) to acetyl-CoA + oxalacetate (OAA). This transport of acetyl-CoA from... 

Hansen, H.O. and Knudsen, J. 1987. Effect of exogenous long-chain fatty acids on individual fatty acid synthesis by dispersed ruminant mammary gland cells. J. Dairy Sci. 70,1350-1354. 

Fatty acids are the building blocks of TAG. More than 90 percent of fatty acids have an even number of carbon atoms, and are in aliphatic chains ranging from 4 to 22 carbons in length. The major fatty acid synthesis pathway is production of stearic acid (18 carbons) after which separate desaturase systems introduce 1, 2, or 3 unsaturated (double) bonds. Additional enzymes become active in elongating the chain as needed. Shorter fatty acids also are produced. Trace amounts of odd-number carbon fatty acids are found in most fats, and also have been synthesized for research purposes. Microorganisms frequently produce odd-number carbon fatty acids, with heptadecenoic (17 carbon) acid a major component of Candida tropicalis yeast fat. Up to 8 percent C17 fatty acids have been found in milk and meat fats of ruminants (cattle, sheep, goats) and are of rumen microbe origin. 

Isomerization of monoenes occurs in microorganisms for a number of reasons. One of these is because isomerization is an essential step in the synthesis of unsaturated fatty acids by anaerobes. A specific dehydrase (P-hydroxydecanoyl-ACP dehydrase) is capable of both dehydration of a 10-carbon intermediate in a growing fatty acyl chain as well as its isomerization from a trans-2 decanoyl-ACP to a af-d-decenoyl-ACP (32). The anaerobic pathway of unsaturated fatty acid synthesis accounts for 1-6% oleic acid in ruminal microorganisms (33). Other anaerobes, such as Streptococcus pneumoniae, isomerize a trans-2 decanoyl-ACP to a r-3-decenoyl-ACP during fatty acid synthesis without catalyzing the dehydration of P-hydroxy intermediates (34). 

Figure 6. Fatty acid synthesis in mammalian tissues showing the transhydrogenation cycle. Pyruvate is generated from glucose in the cytosol (upper portion of figure) and converted to fatty acids by a reaction sequence involving enzymes in the mitochondrial matrix (lower portion of figure). 1, pyruvate carboxylase 2, ATP citrate lyase 3, NADP-malate dehydrogenase. These reactions were absent in adipose tissue from ruminant animals (Hanson and Ballard, 1967).

Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg formation. In most mammals, glucose is the primary substrate for lipogenesis, but in ruminants it is acetate, the main fuel molecule produced by the diet. Critical diseases of the pathway have not been reported in humans. However, inhibition of lipogenesis occurs in type 1 (insulin-de-pendent) diabetes mellitus, and variations in its activity may affect the nature and extent of obesity. 

Trans fatty acids The phospholipids in the plasma and in membranes of all cells contain long-chain polynnsatnrated fatty acids (PUFA). During periods of growth and development of organs, PUFAs are reqnired for phospholipid synthesis. The PUFAs are, of conrse, obtained from dietary triacylglycerol and phospholipids. The donble bonds in most natural fatty acids are cis not trans Nonetheless trans fatty acids do occur in dietary fats. If the diet contains trans fatty acids, they might be incorporated into the phospholipids along with the cis fatty acids and hence into membranes. The presence of these abnormal fatty acids will modify the stmctnre of the phospholipids which conld impair the fnnction of the membrane. There are two main sonrces of trans fatty acids in the diet foods produced from ruminants contain trans fatty... 

One product of the rumen fermentation, methane, is of no value to the ruminant. The major fermentation products used by the ruminant are the short-chain fatty acids, acetate, butyrate and propionate. Acetate and butyrate can be used for energy, but propionate is most useful for the synthesis of protein. If the fermentation could be shifted to reduce methane, acetate and butyrate production and to increase the propionate, the feed efficiency and growth rate could improved. 

The fatty acids in milk fat are derived from two sources, de novo synthesis of fatty acids in the mammary gland and plasma lipids (see Pal-quist, Chapter 2). De novo synthesis generally involves short-chain and medium-chain fatty acids and some 16 0. The proportions of various fatty acids depend on the specific balance between enzymatic chain elongation and chain termination. The plasma lipids are derived from the diet and also from storage in the body tissues. For non-ruminants, the diet has a large influence on the fatty acid composition but for ruminants, biohydrogenation in the rumen results in much less impact of diet on the final fatty acids absorbed into the bloodstream. 

Because the presence of CLA in the human diet is reliant on ruminant products, this chapter first addresses the synthesis of CLA in ruminants. The presence of CLA in ruminant milk and meat is related to rumen fermentation and its synthesis by microorganisms through the process of biohydrogenation (BH) of dietary unsaturated fatty acids. Thus, the effect of diet and processes within the rumen is reviewed. The role of endogenous synthesis of CLA in mammalian tissues has been discovered, and this will be discussed also first as it contributes to the occurrence of CLA in ruminant products and second the significance of endogenous synthesis as a source of CLA in humans and other species. 

---