Use in fatty acid synthesis

In nonphotosynthetic eukaryotes, nearly all the acetyl-CoA used in fatty acid synthesis is formed in mito-... 

Acetyl-CoA synthetase catalyses the conversion of acetic acid to acetyl-CoA ATP + Acetate + CoA - AMP - - Pyrophosphate + Acetyl-CoA Acetyl-CoA can enter the TCA cycle or be used in fatty acid synthesis. 

The pathway is cytoplasmic and results in the production of CO2, but no cfatty acid synthesis. Hence, an increase in activity of the PPP would be expected to result in an increase in the value of the RQ. The two enzymes of the FPF directly involved in NADP reduction are glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, as shown under Thianrdrt in Chapter 9. 

Figure 18.31 Transport of acetyl units and reducing equivalents used in fatty acid synthesis. 

The major source of NADPH used in fatty acid synthesis is the pentose phosphate pathway (PPP). 

Biotin Found widely, egg yolk, Uver, yeast, nuts Coenzyme form used in fatty acid synthesis Dermatitis, muscle werikness... 

Acyl carrier protein (ACP) which contains one phosphate group as part of its structure, is an important co-enzyme used in fatty acid synthesis (Figure 11.16). 

Also a component of the acyl carrier protein used in fatty acid synthesis. Diagnostic test measure blood concentration Dietary sources ubiquitous, present in all foods... 

The overall schematic representation of these reactions is shown in Figure 17. Acetyl-CoA mixes with the acetyl-CoA derived from other metabolic pathways, such as the oxidative decarboxylation of pyruvate or from amino-acid metabolism. However, it seems that acetyl-CoA derived from fatty acid oxidation is not used in fatty acid synthesis since fatty acyl derivatives of CoASH may act as feed-back regulators of fatty acid synthesis. 

The activity of acetyl-CoA carboxylase is modulated allosterically (Section 6.4) by citrate as the positive modulator and palmitoyl-CoA as a negative modulator. The level of citrate is high when both acetyl-CoA and ATP are plentiful and available for use in fatty acid synthesis. High palmitoyl-CoA levels indicate an excess of fatty acids and that fatty acid synthesis is not desirable in the cell at that time. Palmitoyl-CoA reinforces its action on acetyl-CoA carboxylase by inhibiting citrate transport from the mitochondrion and NADPH generation by the pentose phosphate pathway. 

Therefore, we could consider using the Claisen reaction in fatty acid synthesis. 

Pathway of Carbon in Fatty Acid Synthesis Using... 

Insulin also stimulates the storage of excess fuel as fat (Fig. 23-26). In the liver, insulin activates both the oxidation of glucose 6-phosphate to pyruvate via glycolysis and the oxidation of pyruvate to acetyl-CoA. If not oxidized further for energy production, this acetyl-CoA is used for fatty acid synthesis in the liver, and the fatty acids are exported as the TAGs of plasma lipoproteins (VLDLs) to the adipose tissue. Insulin stimulates TAG synthesis in adipocytes, from fatty acids released... 

Isoenzymes III and VII have a more specialized distribution. Carbonic anhydrase III is abundant in adipocytes which use bicarbonate in fatty acid synthesis.7 Isoenzyme V is present in the mitochondrial matrix and is also abundant in both adipocytes and liver.7 8 Isoenzyme IV is a larger membrane-associated form, while VI is secreted into the saliva.10 Carbonic anhydrase has also been identified in E. coli.,11 in a methanobacterium,12 and in green plants.13 133 A 60-kDa carbonic anhydrase called nacrein is found in the organic matrix of the nacreous layer of the pearl oyster, the layer that forms aragonite (orthorhombic calcium carbonate) in the shell and in pearls.14... 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

What are the metabolic sources of NADPH used in fatty acid biosynthesis How many moles of NADPH are required for the synthesis of 1 mole of palmitic acid from acetyl-CoA ... 

In E. coli, phospholipids are used almost exclusively as structural components of the cell membranes, and regulation is known to occur at an early stage in fatty acid synthesis. In the mammalian liver, fatty acids are important precursors of both the structural phospholip-... 

Conversion to fatty acid or ketone bodies. When the cellular energy level is high (ATP in excess), the rate of the citric acid cycle (Topic LI) decreases and acetyl CoA begins to accumulate. Under these conditions, acetyl CoA can be used for fatty acid synthesis or the synthesis of ketone bodies (Topic K3). 

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... 

For the malonate group to be used for fatty acid synthesis, it must first be transferred from malonyl-CoA to malonyl-ACP by the 32.4-kDa monomeric malonyl-CoA ACP transacy-lase, the product of the fabD gene (Fig. 2). A stable malonyl-serine enzyme intermediate is formed during the course of the FabD reaction, and subsequent nucleophilic attack on this ester by the sulfhydryl of ACP yields malonyl-ACP. The high reactivity of the serine in malonyl-ACP transacylase is due to the active site being composed of a nucleophilic elbow as observed in alpha/beta hydrolases. The serine is hydrogen bonded to His-201 in a fashion similar to serine hydrolases. 

Two differences exist between fatty acid and complex polyketide syntheses (Fig. 2). First, in fatty acid synthesis, synthase uses only malonyl moieties as extender units to build an acyl chain. In general, acetate is used as the starter unit in vertebrate fatty acid synthase, but bacterial fatty acid synthase may use a branched-chain carboxylic acid as the starter unit because bacterial fatty acids sometimes contain branched-chain fatty acids. In contrast, polyketide synthesis in bacteria uses malonyl, methylmalonyl, and ethylmalonyl units as extenders. In the polyketide synthase, respective extender units are used at every step of the condensation. The polyketide synthase in fungi uses malonyl units as extenders and methyl groups at a positions are added by C-methylation using 5-adenosyl-L-methionine. 

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