Glucose fatty acid synthesis from

Figure 16-5. Participation of the citric acid cycle in fatty acid synthesis from glucose. See also Figure 21-5.

A) increased fatty acid synthesis from glucose in liver... 

Fig. 1. Pathway of fatty acid synthesis from glucose in animal tissues. The key enzymes or enzyme systems involved are (1) pyruvate dehydrogenase, (2) pyruvate carboxylase, (3) citrate synthase, (4) citrate translocation system, (5) citrate cleavage enzyme, (6) acetyl-CoA carboxylase, (7) fatty acid synthetase, (8) 3-phosphoglyceraldehyde dehydrogenase, (9) malate dehydrogenase, (10) malic enzyme, (11) hexose monophosphate shunt.

Succinate is a much better hydrogen source for liver than for carcass fatty acids in vivo, since the relative metabolization of this carbon-labeled precursor in liver is similar to that of acetate. Hepatic fatty acid synthesis from acetate- K or from succinate- K) is 10% of that of the carcass and their incorporation as percentage of the dose administered in liver is about 10 times higher than that of the glucose-1- or -6- K]. In addition, the ratio obtained in liver fatty acids from... 

Thiamine Thiamine Pyruvate dehydrogenase Fatty-acid synthesis from glucose phytanic... 

Biotin Biocytin Acetyl-CoA carboxylase pyruvate carboxylase Fatty-acid synthesis from glucose... 

Several of the B vitamins are essential for normal fatty-acid metabolism (Table 2). Pantothenic acid is a constituent of CoA and is thus required for numerous reactions of fatty acids. Niacin and riboflavin are necessary for the synthesis of oxidized and reduced NAD(P) and FAD, respectively. These compounds play essential roles in fatty-acid oxidation, synthesis, and elongation. Biotin is a constituent of acetyl-CoA carboxylase and pyruvate carboxylase, both of which are involved in the synthesis of fatty acids from glucose. Thiamine is required for activity of the pyruvate dehydrogenase complex, which also participates in fatty-acid synthesis from glucose. 

There are also microorganisms that can produce poly(HAMCL)s when grown with substrates that are much different from those discussed above, such as glucose [42-44]. The 3HA monomers produced by these microorganisms were most likely obtained from intermediates of the de novo fatty acid synthesis route [45]. PHAs synthesized from unrelated organic substrates are described in Sect. 3.1.2. 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

In common with cholesterol synthesis described in the next section, fatty acids are derived from glucose-derived acetyl-CoA. In the fed state when glucose is plentiful and more than sufficient acetyl-CoA is available to supply the TCA cycle, carbon atoms are transported out of the mitochondrion as citrate (Figure 6.8). Once in the cytosol, citrate lyase forms acetyl-CoA and oxaloacetate (OAA) from the citrate. The OAA cannot re-enter the mitochondrion but is converted into malate by cytosolic malate dehydrogenase (cMDH) and then back into OAA by mitochondrial MDH (mMDH) Acetyl-CoA remains in the cytosol and is available for fatty acid synthesis. 

The basic building block for fatty acid synthesis is acetyl-CoA, produced from glucose, fructose or amino acids (Figure 11.1). Acetyl-CoA formation from these precursors occurs within the mitochondrion and so, because fatty acid synthesis occurs in the cytosol, acetyl-CoA must be transported across the mitochondrial membrane. Trans-... 

Figure 11.1 The precursors for fatty acid synthesis. The immediate precursor is acetyl-CoA, which can be formed from the dietary precursors glucose, fructose or amino acids. The processes are as follows ...

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 ... 

Synthesis of Fatty Acids from Glucose After a person has ingested large amounts of sucrose, the glucose and fructose that exceed caloric requirements are transformed to fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How are these substances produced from glucose ... 

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... 

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). 

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