Oxidative lipolysis

The second way in which fats deteriorate is oxidative lipolysis. This is an entirely different process in which oxygen free radicals add across double bonds. Oxidative rancidity can be prevented or reduced by several different routes. One way is to ensure that no double bonds are present. Another is to use anti-oxidants that act as free radical traps. Exposure to oxygen and ultraviolet light should be avoided. Reducing the temperature has no effect since free radical processes have a zero activation energy. 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Glycerol is released from adipose tissue as a result of lipolysis, and only tissues such as liver and kidney that possess glycerol kinase, which catalyzes the conversion of glycerol to glycerol 3-phosphate, can utihze it. Glycerol 3-phosphate may be oxidized to dihydroxyacetone... 

Cakes are in principle subject to all the threats to a long shelf life that any other bakery product is subject to. The product can dry out, the starch can retrograde or mould can grow. These are in addition to the threats of oxidation, loss of flavour and lipolysis by any enzymes present. 

Fatty acid utilized by muscle may arise from storage triglycerides from either adipose tissue depot or from lipid stores within the muscle itself. Lipolysis of adipose triglyceride in response to hormonal stimulation liberates free fatty acids (see Section 9.6.2) which are transported through the bloodstream to the muscle bound to albumin. Because the enzymes of fatty acid oxidation are located within subcellular organelles (peroxisomes and mitochondria), there is also need for transport of the fatty acid within the muscle cell this is achieved by fatty acid binding proteins (FABPs). Finally, the fatty acid molecules must be translocated across the mitochondrial membranes into the matrix where their catabolism occurs. To achieve this transfer, the fatty acids must first be activated by formation of a coenzyme A derivative, fatty acyl CoA, in a reaction catalysed by acyl CoA synthetase. 

Figure 7.6 Release of fatty acids from the triacylglycerol in adipose tissue and their utilisation by other tissues. Fatty acids are long-chain fatty acids, abbreviated to FFA (see below). Hydrolysis (lipolysis) of triacylglycerol in adipose tissue produces the long-chain fatty acids that are released from the adipocytes into the blood for oxidation by various tissues by P-oxidation (see below).

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

Initially the level of insulin decreases, favouring increased rates of lipolysis, fatty acid oxidation, muscle protein degradation, glycogenolysis and gluconeogenesis. It soon increases, however, as a result of insulin resistance, when the stimulation of the above processes will depend on the cytokine levels. For details of endocrine hormone effects, see Chapter 12. For details of cytokines see Chapter 17. 

Blue cheeses undergo very extensive lipolysis during ripening up to 25% of all fatty acids may be released. The principal lipase in Blue cheese is that produced by Penicillium roqueforti, with minor contributions from indigenous milk lipase and the lipases of starter and non-starter lactic acid bacteria. The free fatty acids contribute directly to the flavour of Blue cheeses but, more importantly, they undergo partial /J-oxidation to alkan-2-ones (methyl O... 

Allosteric activation of hepatic pyruvate carboxylase by acetyl CoA occurs during fasting. As a result of excessive lipolysis in adipose tis sue, the liver is flooded with fatty acids (see p. 328). The rate of for mation of acetyl CoA by p-oxidation of these fatty acids exceeds the capacity of the liver to oxidize it to C02 and H20. As a result, acetyl CoA accumulates and leads to activation of pyruvate carboxylase. [Note Acetyl CoA inhibits pyruvate dehydrogenase (see p. 108). Thus, this single compound can divert pyruvate toward gluconeogenesis and away from the TCA cycle.]... 

In a placebo-controlled study in six patients with type 2 diabetes mellitus thalidomide 150 mg/day for 3 weeks reduced insulin-stimulated glucose uptake by 31% and glycogen synthesis by 48% (1115). However, it had no effect on rates of glycolysis, carbohydrate oxidation, non-oxidative glycolysis, lipolysis, free fatty acid oxidation, or re-esterification. The authors concluded that thalidomide increases insulin resistance in obese patients with type 2 diabetes. 

FAs in plasma - the so-called free fatty acids (FFA) although they are bound to albumin [74] - stem mainly from lipolysis inside the adipocytes and spill-over from the LPL lipolysis [98]. FFA can be taken up and oxidized by most cells, particularly muscle cells [74]. For example the heart lives mainly on fat oxidation [62, 74]. Also the liver takes up FFAs. Some is oxidized, but a large fraction is rebuilt to TG and released to blood as very low density lipoproteins (VLDLs) [74]. The VLDLs undergo the same fate as chylomicrons, but their lipolysis rate is lower. 

Be able to define glycogenesis, glycogenolysis, glycolysis, gluconeogenesis, the Krebs cycle, urea cycle, lipogenesis, lipolysis, and p oxidation and describe how these pathways interact with each other. 

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