Fatty acid synthesizing enzyme

In the clip, Lorenzo s father used models such as paper clips to help him understand how the enzyme worked. Explain how Lorenzo s Oil alters the function of the fatty acid synthesizing enzyme. 

If the chloroplast can be considered a variant of a proplastid with a photosynthetic capability, then this organelle should and does have the same complement of fatty acid-synthesizing enzymes as the proplastid fiom nonphotosynthetic tissue (Stumpf, 1977). Indeed, recent work in the author s... 

The chemical nature of the central sulfhydryl group was then elucidated by the brilliant studies of Roy Vagelos on the acyl carrier protein isolated from E. coli. In these studies it was discovered that the central group is represented by 4 -phospho-pantetheine attached in phosphodiester linkage to a serine residue of the protein. In addition, the studies on the fatty acid synthesizing enzyme system from E. coli (cf. ref. 25), where the component enzymes fail to show any signs of physical interaction at the cell-free level, fully confirmed and at the same time refined our scheme of fatty acid biosynthesis as presented in 1961.< ... 

Hydroxy- 9-methylglutaryl CoA further yields acetyl CoA and acetoacetic acid, as was shown earlier by Coon et cU. (I48). In biotin deficiency the carboxylation reaction does not occur. It was shown by Lynen et al. that the actual carboxylation is preceded by the enzymic dehydration (rf jS-hydroxyisovaleryl CoA to /8-methylcrotonyl CoA, which is the true substrate for the entry of CO2. TTiis occurs at the expense of the hydrolysis of the terminal P04 of ATP. The unsaturated intermediate is then saturated by the addition of H2O to yield the final product. The critical step of this carboxylation is the conversion of CO2 to a reactive form. The analogy of the biochemical activation of other substances through an acyl adenylate type of compound did not fit CO2 activation. The final mechanism of the activation of CO2 was derived from the discovery that the carboxylase enzyme was a biotin-protein. This observation explains earlier work 149) which indicated that biotin is a cofactor of the fatty acid-synthesizing enzyme system. When the purified carboxylase was incubated with P and ATP an exchange reaction of phosphate occurred, which was inhibited by avidin, a protein which specifically binds biotin. This indicated that the primary reaction in CO2 fixation is the combination of ATP with the biotin-protein enzyme to yield ADP biotin-protein -f P. The active CO2 is then the product of an exchange reaction between ADP and C02 which is finally attached to the biotin-protein complex. 

In Box 7.13 we saw that the widely used analgesic aspirin exerted its action by acetylating the enzyme cyclooxygenase (COX) which is involved in the production of prostaglandins. Prostaglandins are modified C20 fatty acids synthesized in animal tissues and they affect a wide variety of physiological processes, such as... 

Pantothenic acid (8.48), a hydroxyamide, occurs mainly in liver, yeast, vegetables, and milk, but also in just about every other food source, as its name implies [pantos (Greek) = everywhere]. It is part of coenzyme A, the acyl-transporting enzyme of the Krebs cycle and lipid syntheses, as well as a constituent of the acyl carrier protein in the fatty-acid synthase enzyme complex. 

New (de novo) fatty acids are synthesized from two-carbon acetyl units produced during metabolism. Two enzyme complexes, acetyl-coenzyme A carboxylase and fatty acid synthetase, work in concert to build up fatty acid chains, two carbons at a time, until released by the complex. The primer in plants and animals is essentially a two-carbon acetyl group and the fatty acid chains have even numbers of carbons. If the primer is a three-carbon propionate group, odd-number carbon chains result. Odd-number fatty acids are common in microbial lipids and also are synthesized de novo from propionic VFA by rumen bacteria and deposited in adipose tissue. The length of the fatty acid synthesized depends on the tissue. Palmitic acid is produced in the liver and adipose tissue, and shorter-chain fatty acids are also produced in the mammary glands (49). 

Fig. 13.12 Polyunsaturated fatty acids required for eicosanoid synthesis. Oleic acid is the only fatty acid synthesized by mammals de novo. Linoleic (co-3) and a-linolenic acid (9 or greater fatty acids. Ingested o>3 fatty acids are metabolized to other co-3 fatty acids with o>9 double bonds. The same applies to co-6 fatty acids. The major dietary sources of polyunsaturated fatty acids are fish and plants oils...

Mammals are dependent on dietary sources of essential fatty acids as they lack the desaturase enzymes necessary to synthesize them. Kao et al. (2006) engineered transgenic mice expressing the ffl-3 fatty acid desaturase enzyme from the nematode Caenorhabditis elegans, which synthesizes a wide range of PUFA and possesses the only known example of an ffl-3 desaturase enzyme in the animal kingdom. The milk from these mice had more ffl-3 and less ffl-6 PUFA, and hence had showed an overall decrease in the ffl-6 ffl-3 PUFA ratio in the milk. The milk phospholipids from the transgenic mice had an ffl-6 ffl-3 ratio of 1.78 as compared to 9.82 in the control animals. The authors anticipate that this maybe a suitable method to improve the nutritional profile of dairy-based diets. 

The fatty acids synthesized in the plastid are exported to the cytoplasmic compartment as acyl- CoAs generated by enzymic activity of the outer membrane of the plastid envelope. These acyl- CoAs are utilized in the synthesis of phospholipids in the mitochondria and the endoplasmic reticulum. The fatty acid specificity in the synthesis of phosphatidyl choline (PC) is such that palmitate (16 0) is never found at the sn-2 position. Thus the predominant molecular species are sn1-l8, sn2-l8 and sn1-l6, sn2-l8. These molecular species of PC supply the diaoylglycerol (DAG) moiety for synthesis of MGDG, DGDG, and SQDG in the plastid. 

The peroxisomal 3-oxoacyl-CoA thiolase (thiolase) is the last enzyme involved in the P-oxidation of fatty acids. The enzyme cleaves long chain fatty acyl-CoA to generate acetyl-CoA and shortened acyl-CoA. The enzyme is nuclear encoded, synthesized in the cytoplasm and transported into peroxisomes. The thiolase B gene is inducible by the peroxisome proliferator compounds, like other genes involved in P-oxidation of fatty acids in peroxisomes. 

Acetyl-CoA is the source of the carbon atoms for the synthesis of cholesterol, steroid hormones, and fatty acids. Various enzymes catalyze biological versions of aldol reactions and Claisen condensations during the syntheses of these compounds. 

An explanation for the fact that the fatty acids synthesized by the soluble animal and yeast systems are of relatively uniform chain length has been given by Lynen et al. [250]. It is reasoned that the probabihty of chain termination is enhanced—that is, deacylation or transfer to CoA—as the residence time of the saturated acyl group on pantetheine prosthetic group is increased. The interaction of the elongated, hence more hydrophobic, acyl group with a site on the enzyme would tend to increase the residence time and thereby favor chain termination rather than condensation and further elongation. 

The outer membrane contains the enzymes that are responsible for the desaturation and elongation of fatty acids synthesized in the cytosol (section 5.6.1.1), the enzymes for triacylglycerol synthesis from fatty acids (section 5.6.1.2) and phospholipases that catalyse the hydrolysis of phospholipids (section 4.3.1-2). 

The major unsaturated fatty acids synthesized by N-limited R.gracilis are oleic, linoleic and a-linolenic acids, indicating the presence of A9, A12 and A15 desaturase enzymes [1]. In this report, we discuss experiments In which the activities of these desaturase systems have been altered by temperature and sterculate treatment. 

Therefore, both enzyme activities have been compared in extracts (Table 3). Both seed materials showed similar ACS-activities as spinach chloroplasts. It appears of interest, however, that- like the total fatty acid synthesizing capacity- the ACC- activities of Cuphea wrightii seeds were 10-fold higher than in Cuphea racemosa and spinach chloroplasts. 

Table 1. Relationship between fatty acid synthesizing activity and the related enzyme activities...

The rich diversity of fatty acids found in the triglycerides of the seed oil contrasts markedly with the relatiely simple fatty acid spectrum observed in the membrane polar lipid fraction. This implies that fatty acids synthesized novo in the chloroplast and plastids are subsequently modified in other enzyme catalysed reactions. The steps associated with many of these reactions are unknown as are the mechanisms whereby they end up in the oil rather than the various membranes. 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

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