Lipid metabolism catabolism

PLTP is responsible for the majority of phospholipid transfer activity in human plasma. Specifically, it transfers surface phospholipids from VLDL to HDL upon lipolysis of triglycerides present in VLDL. The exact mechanism by which PLTP exerts its activity is yet unknown. The best indications for an important role in lipid metabolism have been gained from knockout experiments in mice, which show severe reduction of plasma levels of HDL-C and apoA-I. This is most likely the result of increased catabolism of HDL particles that are small in size as a result of phospholipid depletion. In addition to the maintenance of normal plasma HDL-C and apoA-I concentration, PLTP is also involved in a process called HDL conversion. Shortly summarized, this cascade of processes leads to fusion of HDL... 

Gerhard B (1993) Catabolism of fatty acid acids. In Moore TS (ed) Lipid metabolism in plants. CRS Press, Baton Rouge, p 527... 

A natural question is "Why has this complex pathway evolved to do something that could have been done much more directly " One possibility is that the presence of too much malonyl-CoA, the product of the P oxidation pathway of propionate metabolism (Fig. 17-3, pathways a and c), would interfere with lipid metabolism. Malonyl-CoA is formed in the cytosol during fatty acid biosynthesis and retards mitochondrial P oxidation by inhibiting carnitine palmitoyltransferase i.46 70a 75 However, a relationship to mitochondrial propionate catabolism is not clear. 

Pantothenic acid participates as part of coenzvme A in carbohydrate metabolism (2-carbon transfer-acetate, or pyruvate), lipid metabolism (biosynthesis and catabolism of fatty acids, sterols, +phospholipids), protein metabolism (acetylations of amines and amino acids), porphyrin metabolism, acetylcholine production, isoprene production. 

In addition to being incorporated into tissue proteins, amino acids, after losing their nitrogen atoms by deamination and/or transamination, may be catabolized to yield energy or to form glucose. Conversely, the nonessential amino acids may be synthesized from carbohydrate metabolism intermediates and ammonia or from essential amino acids. This section is devoted to the mechanisms of such metabolic processes and their interrelationships with carbohydrate and lipid metabolic pathways. 

Although several lipoproteins are considered to play a role in atherogenesis [VLDL, LDL and Lp(a)j, LDL cholesterol (LDL-C) is the primary target of therapy. The risk of CHD is inversely related to levels of HDL, because HDL is responsible for reverse cholesterol transport. Lipoprotein disorders can involve abnormalities in lipid metabolism (e.g., synthesis, transport, and catabolism). Attainment of a lipid profile must be made after a 9- to 12-hour fast. 

This mitochondrial reaction permits the final steps in the catabolism of the branched-chain amino acid leucine. The final products, acetoacetate and acetyl CoA, either are oxidative metabolized to carbon dioxide and water or enter other reactions in lipid metabolism. 

In addition to SREBPs, several members of the nuclear receptor superfamily regulate lipid metabolism. Nuclear receptors are transcription factors that are generally activated when bound to specific small-molecule ligands (Chapter 11). Certain nuclear receptors influence whole-body lipid metabolism by regulating the absorption of dietary lipids, cellular synthesis of lipids, transport protein-mediated import and export of lipids, levels of lipoproteins and their receptors, and catabolism of lipids (e.g., fatty acid oxidation in the peroxisome) and their secretion from the body. 

Thyroid hormone effects on metabolism arc diverse. The rates of protein and carbohydrate synthesis and catabolism are inlluenced. An example of the effect of thyroid hormones on lipid metabolism is the observation of a high serum cholesterol in some hypothyroid patients. This is a consequence of a reduction in cholesterol metabolism due to down regulation of low-density lipoprotein (LDL) receptors on liver cell membranes, with a subsequent failure of sterol excretion via the gut. 

Our knowledge of lipolytic enzymes in plants is meager. This is surprising, perhaps, when the commercial importance of seed oils and other plant lipids is considered. In addition to the obvious importance of lipid metabolism in oil seed crops, the involvement of storage and membrane lipids in plant biochemistry and its applications should be backed by a much better understanding of lipid catabolism. The surface lipids of all plants have been almost totally neglected in this respect until the recent developments described by Kolattukudy (this volume. Chapter 18). 

Effect on Lipid Metabolism. Our knowledge of the effect of cortisone on lipid metabolism is still fragmentary. Interpretation of the results is complicated by the fact that the effect of the hormone seems to vary depending upon the source of the adipose tissue. Adrenalectomy stimulates and corticoid injections decrease lipogenesis in the adipose tissue of the mesentery. The decreased lipogenesis induced by corticosteroids is accompanied by release of free fatty acids. When corticosterone and hydrocortisone are added to epididymal adipose tissue incubated in vitro, the hormones fail to stimulate lipogenesis from [ " Cjpyruvate, but they accelerate fatty acid release, and the lipolytic effect is completetly blocked by actinomycin D. Consequently, one effect of glucocorticoids on some of the adipose tissues seems to be to accentuate lipid catabolism. 

Apolipoproteins of the C group are peptides of small molecular weights, present in chylomicrons, VLDL, IDL, and HDL. These polypeptides have common characteristics they are regulators (activators or inhibitors) of the lipid metabolism of lipoproteins, particularly the catabolism of triglyceride-rich hpoproteins [1]. The distribution of the different Apo C in lipoprotein classes varies between normal subjects and hypertriglyceridemics and in relation to fasting and the type of diet. 

Gerhardt, B. and Kleiter, A (1995) Peroxisomal catabolism of linoleic acid, in J.-C. Kader and P. Mazliak (eds.). Plant Lipid Metabolism, Kluwer Academic Publishers, Dordrecht, pp. 265-267. 

Decarboxylases function in the synthesis of major neurotransmitters (26) adequate PLP supply in brain tissue is therefore essential for normal brain function. Aminotransferases have a key function in both amino acid biosynthesis and catabolism. PLP has also a structural function (27) in glycogen phosphorylase (EC 2.4.1.1), and a role for PLP in lipid metabolism has been proposed (28,29). 

The long chain acyl-CoA synthetases are firmly membrane bound and can only be solubilized by the use of detergents. Within the cell, activity has been detected in endoplasmic reticulum and the outer mitochondrial membrane with small amounts in peroxisomes (when the latter are present). There is some dispute as to whether the activity present in mitochondrial and microsomal fractions is due to the same enzyme. Because long chain fatty acid activation is needed for both catabolism ( -oxidation) and for synthesis (acylation of complex lipids) it would be logical if the long chain acyl-CoA synthetases of mitochondria and the endoplasmic reticulum formed different pools of cellular acyl-CoA. This compartmentation has been demonstrated with yeast mutants where it plays a regulatory role in lipid metabolism (section 3.2.7) and, perhaps, in other organisms. 

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