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1.7 Glycan biosynthesis and metabolism
-Genetic deficiencies in conversion of cholesterol to bile acids are treated with exogenous chenodeoxycholic acid.
Composition of plasma lipoproteins
-Neutral lipid core (TAG and cholesteryl esters) surrounded by amphipathic apolipoproteins, phospholipid, and nonesterified (free) cholesterol
-Amphipathic compounds are oriented so their polar portions are exposed on the surface (soluble).
-TAG and cholesterol are obtained fromdiet (exogenous source) or from de novo synthesis (endogenous source)
-Recognition sites for cell-surface receptors
-Activators or coenzymes for enzymes involved in lipoprotein metabolism.
-Required as essential structural components of the particles or can be transferred freely between lipoproteins.
Apart from direct physiological measurements, Ins/IGF-mutant metabolism was also studied by analyzing transcriptional profiles of metabolism-related genes. ) found that, in mutants, gluconeogenesis, glyoxylate pathway activity and trehalose biosynthesis were upregulated relative to the appropriate controls ( versus adults). These authors found similar qualitative changes in dauer larvae compared to recovered dauer larvae. Unlike dauer stage animals, TCA-cycle and respiratory chain activities were not downregulated in mutants, supporting the physiological data discussed above (). In addition, in part explanation for the high ATP levels found in these mutants, the mitochondrial F1-ATPase inhibitor protein (IF1), which specifically inhibits the ATPase activity of ATP synthase under anoxic conditions, was found to be upregulated in .
Biosynthesis of Cholesterol, Metabolism of Lipids.
Under aerobic conditions (), will metabolize energy through the standard metabolic pathways. In glycolysis, a series of enzymatic reactions will convert sugars (typically glucose) to pyruvate. During this process, small amounts of ATP are generated and electron carriers are loaded with electrons (NAD+ is reduced to NADH + H+). Consequently, pyruvate is translocated to the mitochondria, decarboxylated and converted into acetyl-CoA. In this process the first completely oxidized carbon is released as CO2. Acetyl-CoA then enters the tricarboxylic acid (TCA) cycle by condensing with oxaloacetate to form citrate. A series of oxidation reactions then ensue with the result that two carbons are expelled as CO2, (G/A)TP is produced and the electron carriers (NAD+ and FAD+) are reduced. Finally, the cycle is completed when oxaloacetate is formed. The electron carriers that were reduced during glycolysis and the TCA cycle deliver their electrons to O2 (with the formation of water) through a series of electron transport chain redox proteins located in the inner mitochondrial membrane. During electron transfer, some of these redox proteins shuttle protons from the mitochondrial matrix to the intramembrane space of the mitochondria, thereby creating an electrochemical gradient. The potential energy in this gradient is finally used by ATP-synthase (another protein complex in the inner mitochondrial membrane) to drive ATP synthesis.
Lipids and amino acids can also be used as energy sources, but they enter the main pathways at different points. has a functional methylmalonyl-CoA epimerase (racemase) that is involved in propionyl-CoA metabolism for the degradation of branched amino acids and odd-chain fatty acids (). Fatty acid moieties of lipids are broken down by -oxidation into acetyl-CoA (which in turn can enter the TCA cycle). -oxidation occurs in the mitochondrial matrix and also yields reduced electron carriers. Peroxisomal -oxidation of long-chain fatty acids is not linked directly to energy metabolism because the reduced electron carrier is directly oxidized by molecular oxygen (yielding hydrogen peroxide). Amino acids can be broken down via distinct pathways and their carbon skeletons can be metabolized in the TCA cycle.
Biosynthesis of Cholesterol, Steroids, and Isoprenoids
It blocks the uptake of cholesterol by competing with its bind to intestinal mucosal cell membranes (negative feedback)
Cholesterol, Lipoprotein, and Steroid Metabolism
Regulation of Cholesterol Synthesis
-HMG CoA reductase is the major control point for cholesterol biosynthesis
and all other nematodes studied to date lack the capacity to synthesize sterols from acetate (; ). This requirement can be met by providing exogenous cholesterol, -sitosterol, 7-dehydrocholesterol, ergosterol, or stigmasterol (; ). Indeed, can use various dietary sterols, including plant sterols (). and species have the capacity to synthesize lanosterol from squalene 2,3-oxide; the major metabolic block in the pathway of sterol biosynthesis likely occurs between farnesol (and any other steps before farnesol) and squalene (; ). More recently, ) constructed a strain expressing human dehydrocholesterol reductase, which enabled the worms to convert exogenous 7-dehydrocholesterol into cholesterol. This transgenic strain was slightly longer-lived and stress-resistant, but showed reduced fecundity.
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High Cholesterol and Metabolism – Functional …
According to the definition provided above, metabolism includes every cellular process, ranging from DNA replication to transcription and translation to enzyme function, and also involves the chemistry of small molecules in the cell. In this chapter, we will focus on intermediary metabolism, which describes all reactions concerned with the storage and generation of metabolic energy required for the biosynthesis of low-molecular weight compounds and energy storage compounds (). In the intermediary metabolism pathway, the structure of each enzyme plays a crucial role in determining the specific properties of each reaction.
High Cholesterol and Metabolism
The intermediary metabolic network is well conserved among eukaryotes and the major metabolic pathways found in heterotrophic organisms are also present in (). In the first section of this chapter, we will elaborate on the characteristics of these general pathways in our model. We will subsequently focus on the vital compounds that cannot be synthesized by and hence need to be extracted from the environment. Vitamins, essential amino acids and other related compounds will be discussed in the section about nutritional requirements. At the end of this chapter, a short overview will also be given describing the different metabolic waste products and the storage and production of metabolic energy in .
Androstenedione and testosterone biosynthesis and metabolism part 1
In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed.
Cholesterol: Synthesis, Metabolism, Regulation
We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.
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