P oxidation

It s called P oxidation, and by way of explanation In the mitochondrial matrix is the major part. 

It starts however on the cytosolic side With fatty acids coming from triglyceride Activated in the thiokinase way To thioester of CoA. 

But a transferase now comes upon the scene Making fatty acyl carnitine. 

And there now is permeation, and a new transacylation Generating acyl CoA in the matrix space. 

We now begin upon an oxidation phase With FAD-dependent dehydrogenase (The flavoprotein is oxidised again By ETF, thence by the chain). 

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Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

Alcohol sulfates are easily metabolized by mammals and fishes either by oral or intraperitoneal and intravenous administration. Several labeled 35S and 14C alcohol sulfates have been used to determine their metabolism in experiments with rats [336-340], dogs [339], swines [341], goldfish [342], and humans [339]. From all of these studies it can be concluded that alcohol sulfates are absorbed in the intestine of mammals and readily metabolized by to and p oxidation of the alkyl chain and excreted in the urine and feces, but are also partially exhaled as carbon dioxide. Fishes absorb alcohol sulfates through their gills and metabolize them in a similar way to that of mammals. 

Figure 2. Mechanism of PDH. The three different subunits of the PDH complex in the mitochondrial matrix (E, pyruvate decarboxylase E2, dihydrolipoamide acyltrans-ferase Ej, dihydrolipoamide dehydrogenase) catalyze the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2. E, decarboxylates pyruvate and transfers the acetyl-group to lipoamide. Lipoamide is linked to the group of a lysine residue to E2 to form a flexible chain which rotates between the active sites of E, E2, and E3. E2 then transfers the acetyl-group from lipoamide to CoASH leaving the lipoamide in the reduced form. This in turn is oxidized by E3, which is an NAD-dependent (low potential) flavoprotein, completing the catalytic cycle. PDH activity is controlled in two ways by product inhibition by NADH and acetyl-CoA formed from pyruvate (or by P-oxidation), and by inactivation by phosphorylation of Ej by a specific ATP-de-pendent protein kinase associated with the complex, or activation by dephosphorylation by a specific phosphoprotein phosphatase. The phosphatase is activated by increases in the concentration of Ca in the matrix. The combination of insulin with its cell surface receptor activates PDH by activating the phosphatase by an unknown mechanism.

Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ...

It has often been questioned whether the rates and kinetics of purified enzymes, determined in very dilute solutions with high concentrations of their substrates, but not always of their cofactors, can be extrapolated to the conditions prevailing in the matrix. Much of the mitochondrial water will be bound to protein by hydrogen bonds and electrostatically, but there is also a pool of free water which may only be a fraction of the total water (Gitomer, 1987). The molar concentrations of intermediates of the citrate cycle and of p-oxidation are very low, usually less than those of most enzymes (Srere, 1987 Watmough et al., 1989 Sumegi et al., 1991). The extent to which cofactors and intermediates bind specifically or nonspecifically to enzymes is not known. It is therefore difficult to estimate concentration of these... 

Osmundsen, H. Hovik, R. (1988). P-Oxidation of polyunsaturated fatty acids. Biochem. Soc. Trans. 16,420-422. 

Sumegi, B., Porpaczy, Z., Alkonyi, 1. (1991). Kinetic advantage of the interaction between the fatty acid P-oxidation enzymes and the complexes of the respiratory chain. Biochim. Biophys. Acta 1081, 121-128. 

Uchicda, Y., Izai, K., Orii, T., Hashimoto, T. (1992). Novel fatty acid p-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hy-droxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein. J. Biol. Chem. 267, 1034-1041. 

Watmough, N.J.. Turnbull, D.M., Sherratt. H.S.A. Bartlett. K. (1989). Measurement of the acyl-CoA intermediates of p-oxidation by hplc with on-line radiochemical and photodiode-array detection. Application to the study of [U- C]hexadecanoate by intact rat liver mitochondria. Biochem. J. 262,261-269. 

The source of long-chain fatty acids is either dietary lipid or de novo synthesis from acetyi-CoA derived from carbohydrate. Fatty acids may be oxidized to acetyl-CoA (P-oxidation) or esterifred with glycerol, forming triacylglycerol (fat) as the body s main fuel reserve. 

Acetyl-CoA formed by P-oxidation may undergo several fates ... 

The central role of the mitochondrion is immediately apparent, since it acts as the focus of carbohydrate, hpid, and amino acid metabohsm. It contains the enzymes of the citric acid cycle, P-oxidation of fatty acids, and ketogenesis, as well as the respiratory chain and ATP synthase. 

The onward metabohsm of succinate, leading to the regeneration of oxaloacetate, is the same sequence of chemical reactions as occurs in the P-oxidation of fatty acids dehydrogenation to form a carbon-carbon double bond, addition of water to form a hydroxyl group, and a hirther dehydrogenation to yield the oxo- group of oxaloacetate. 

Carnitine (p-hydroxy-y-trimethylammonium butyrate), (CHjljN"—CH2—CH(OH)—CH2—COO , is widely distributed and is particularly abundant in muscle. Long-chain acyl-CoA (or FFA) will not penetrate the inner membrane of mitochondria. However, carnitine palmitoyltransferase-I, present in the outer mitochondrial membrane, converts long-chain acyl-CoA to acylcarnitine, which is able to penetrate the inner membrane and gain access to the P-oxidation system of enzymes (Figure 22-1). Carnitine-acylcar-nitine translocase acts as an inner membrane exchange transporter. Acylcarnitine is transported in, coupled with the transport out of one molecule of carnitine. The acylcarnitine then reacts with CoA, cat-... 

In P-oxidation (Figure 22-2), two carbons at a time are cleaved from acyl-CoA molecules, starting at the carboxyl end. The chain is broken between the 0t(2)- and P(3)-carbon atoms—hence the name P-oxidation. The two-carbon units formed are acetyl-CoA thus, palmi-toyl-CoA forms eight acetyl-CoA molecules. 

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