Very long-chain acids

In suberizing potato tuber disks, labeled oleic acid was incorporated into co-hy-droxyoleic acid and the corresponding dicarboxylic acid, the two major aliphatic components of potato suberin [73]. Exogenous labeled acetate was also incorporated into all of the aliphatic components of suberin, including the very long chain acids and alcohols in the wound-healing potato slices. The time-course of incorporation of the labeled precursors into the suberin components was consistent with the time-course of suberization. The biosynthetic pathway for the major aliphatic components of suberin is shown in Fig. 8a. 

Some materials, e.g. beeswax and other materials containing very long-chain acids, need longer boiling. If in doubt, set up several samples and boil for 1, 2, 3, etc. hours. When two consecutive results agree within reasonable experimental error, saponification is complete. 

Without carbon, the basis for life would be impossible. While it has been thought that silicon might take the place of carbon in forming a host of similar compounds, it is now not possible to form stable compounds with very long chains of silicon atoms. The atmosphere of Mars contains 96.2% CO2. Some of the most important compounds of carbon are carbon dioxide (CO2), carbon monoxide (CO), carbon disulfide (CS2), chloroform (CHCb), carbon tetrachloride (CCk), methane (CHr), ethylene (C2H4), acetylene (C2H2), benzene (CeHe), acetic acid (CHsCOOH), and their derivatives. 

Fatty acid transport protein paralogues 1-6 FATP 1-6 Gene symbols SLC27A1-6 Solute carrier family 27A Very long-chain acyl-CoA synthetase VLCS... 

Fatty acid transport proteins (FATPs) are an evolutionary conserved family of integral membrane proteins found at the plasma membrane and on internal membranes. FATPs facilitate the unidirectional uptake and/ or intracellular activation of unesterified long-chain and very long-chain fatty acids (LCFAs) into a variety of lipid-metabolizing cells and tissues. 

In vitro and ex vivo studies have shown that FATPs transport LCFAs and very long-chain fatty acids (VLCFAs) but no medium-chain fatty acids, fatty acid esters, or lipid-soluble vitamins [4]. LCFA transport is inhibited by prior protease treatment. Synthetic substrates for FATPs include 14C-labeled fatty acids and the fluorescently labeled fatty acid analogue C1 -BODEP Y-Cl 2. Using the latter substrate, differences in fatty acid uptake kinetics between FATP expressing 3T3 LI adipocytes and 3T3 LI fibroblasts, which are devoid of FATPs, can be readily appreciated (Fig. 2). 

Long-chain fatty acids (LCFAs) are aliphatic compounds with a terminal carboxyl group and with a chain length greater than 12 carbon atoms (e.g., lauric acid). Very long-chain fatty acids are fatty acids with more than 18 carbon atoms (e.g., stearic acid). 

A few of the important reactions carboxylic acids undergo are shown above. Soap is made by reacting sodium or potassium hydroxide with long-chain acids such as C17H35COOH (stearic acid). Acid chlorides and acid anhydrides are more reactive than their corresponding carboxylic acids and are used in the chemical industry to make various acid derivatives. A very important industrial reaction is the reaction of carboxylic acids (or the chlorides or anhydrides) with alcohols to form esters. 

Peroxisomes Oxidize Very Long Chain Fatty Acids... 

A modified form of P-oxidation is found in peroxisomes and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by catalase. Thus, this dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP. The system facilitates the oxidation of very long chain fatty acids (eg, Cjq, C22). These enzymes are induced by... 

Interest in import of proteins into peroxisomes has been stimulated by studies on Zellweger syndrome. This condition is apparent at birth and is characterized by profound neurologic impairment, victims often dying within a year. The number of peroxisomes can vary from being almost normal to being virtually absent in some patients. Biochemical findings include an accumulation of very long chain fatty acids, abnormalities of... 

Yano, I. Analysis of bacterial metabolites and components by computerized GC/MS system—From shorter chain acids to very long-chain compounds up to C80. Rapid Meth. Autom. Microbiol. Immunol. (4th Int. Symp.) 1985,239-247. 

Very long-chain (C,n-C9S) acids Rare and minor Common and substantial... 

The unique suberin components that are not found as significant components of cutin are the very long chain molecules and the dicarboxylic acids. Therefore, chain elongation and conversion of co-hydroxy acids to the corresponding dicarboxylic acids constitute two unique biochemical processes involved in the synthesis of suberin. Incorporation of labeled acetate into the very long chain components of suberin was demonstrated and this ability developed during suberization in potato tuber disks [73]. The enzymes involved... 

How the aliphatic monomers are incorporated into the suberin polymer is not known. Presumably, activated co-hydroxy acids and dicarboxylic acids are ester-ified to the hydroxyl groups as found in cutin biosynthesis. The long chain fatty alcohols might be incorporated into suberin via esterification with phenylpro-panoic acids such as ferulic acid, followed by peroxidase-catalyzed polymerization of the phenolic derivative. This suggestion is based on the finding that ferulic acid esters of very long chain fatty alcohols are frequently found in sub-erin-associated waxes. The recently cloned hydroxycinnamoyl-CoA tyramine N-(hydroxycinnamoyl) transferase [77] may produce a tyramide derivative of the phenolic compound that may then be incorporated into the polymer by a peroxidase. The glycerol triester composed of a fatty acid, caffeic acid and a>-hydroxy acid found in the suberin associated wax [40] may also be incorporated into the polymer by a peroxidase. 

Herrmann, T., et al. Mouse fatty acid transport protein 4 (FATP4) characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene 2001, 270,... 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

Adrenoleukodystrophy is an X-linked dysmyelinative disorder caused by mutations in the ABCD1 gene, which encodes the peroxisomal integral membrane ALD protein, a member of the ATP binding cassette transporter family. These mutations result in impaired clearance of plasma very-long-chain fatty acids. Affected males may present with symmetrical distal axonal polyneuropathy, adrenocortical insufficiency or CNS demyelination, while occasional heterozygous women demonstrate deficits suggestive of multiple sclerosis [56]. Manipulation of dietary fatty acid intake has some minimal therapeutic effect, while bone marrow transplantation has diminished deficits in a few patients. (See in Ch. 41.)... 

Adrenoleukodystrophy X-linked Peroxisomal membrane protein in the ABC transporter family Decreased peroxidation of saturated, very-long-chain fatty acids, causing their accumulation in brain, adrenals and other tissues variable phenotypes with regard to hypomyelination see text 1,26, Ch. 40... 

Alkyl PAT, alkyl-dihydroxy phosphate synthase Bif, bifunctional enzyme DHAPAT, dihydroxyphosphate acyltransferase deficiency DHCA, dihydroxycholestanoic acid N, normal nd, not determined Ox, acyl-CoA oxidase Rac, 2-methylacyl-CoA racemase RCDP, rhizomelic chondrodysplasia punctata Ref, Refsum s disease THCA, trihydroxycholestanoic acid VLCFA, very-long-chain fatty acid. 

Through the formation of polypeptide bonds between amino acids, very long chains of sequences are obtained. Generally, proteins consist of hundreds and thousands of amino acids. For example, human hemoglobin has four polypeptide chains, of which two are cf-chains and two are j3-chains. There are 141 amino acids in each a-chain with a sequence of... 

A separate very long-chain-acyl-CoA synthetase is present in peroxisomes for the activation of very long-chain fatty acids, such as arachidonate (20 carbon atoms). These fatty acids are degraded exclusively in the peroxisomes. 

Peroxisomes are organelles which are bounded by a single membrane. They are present in the Uver where very long-chain fatty acids are oxidised by P-oxidation in peroxisomes, which is different from mitochondrial oxidation. 

The capacity of P-oxidation in about 10% of that in the mitochondria but it plays an important role in oxidising unusual fatty acids for example, very long-chain fatty acids, polyunsaturated fatty acids, dicarbox-ylic fatty acids. 

F. Oxidation of very long-chain fatty acids (VLCFAs), ie, fatty acids having >22 carbons, requires special enzymes located in the peroxisome. 

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