23 matches Biochemistry EIGHTH EDITION Jeremy M. Berg John L. Tymoczko Gregory J. Gatto, Jr. Lubert Stryer Publisher: Kate Ahr Parker Senior Acquisitions. Biochemistry 5th ed – Jeremy M. Berg, John L. Tymoczko, Lubert Stryer – dokument [*.pdf] Dedication About the authors Preface Tools and Techniques Clinical. Biochemia – Stryer – Ebook download as PDF File .pdf) or read book online.
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Peripheral tissues gain access to the lipid energy reserves stored in adipose tissue through three stages of processing. First, the lipids must be mobilized. In this process, triacylglycerols are degraded to fatty acids and glycerol, which are released from the adipose tissue and transported to the energy-requiring tissues. Second, at these tissues, the fatty acids must be activated and transported into mitochondria for degradation. Third, the fatty acids are broken down in a step-by-step fashion into acetyl CoAwhich biocemia then processed niochemia the citric acid cycle.
The initial event in the utilization of fat as an energy source is the hydrolysis of triacylglycerols by lipases, an event referred to as lipolysis. The lipase of adipose tissue are activated on treatment of these cells with the hormones epinephrine, norepinephrine, glucagon, and adrenocorticotropic hormone. tymoczkl
Biochemia (Book, ) 
In adipose cells, these hormones trigger 7TM receptors that activate adenylate cyclase Section The increased biochemi of cyclic AMP then stimulates protein kinase Awhich activates the lipases by phosphorylating them. Thus, epinephrine, biochemiia, glucagon, and adrenocorticotropic hormone induce lipolysis Figure In contrast, insulin inhibits lipolysis.
The released fatty acids are not soluble in blood plasma, and so, on release, serum albumin binds the fatty acids and serves as a carrier.
By these means, free fatty acids are made accessible as biochenia fuel in other tissues. Triacylglycerols in adipose tissue are converted into free fatty acids and glycerol for release into the bloodstream in response to hormonal signals. A hormone-sensitive lipase initiates the process. Glycerol formed by lipolysis is absorbed by the liver and phosphorylated, oxidized to dihydroxyacetone phosphate, and then isomerized to glyceraldehyde 3-phosphate.
This molecule is an intermediate in both the glycolytic and the gluconeogenic pathways. Hence, glycerol can be converted into pyruvate or glucose in the liver, which contains the appropriate enzymes. The reverse process can take place by the reduction of dihydroxyacetone phosphate to glycerol 3-phosphate.
Hydrolysis by a phosphatase then gives glycerol. Thus, glycerol and glycolytic tymovzko are readily interconvertible. Eugene Kennedy and Albert Lehninger showed in that fatty acids are oxidized in mitochondria.
Subsequent work demonstrated that they are activated before they enter the mitochondrial matrix. Adenosine triphosphate ATP drives the formation of a thioester linkage between the carboxyl group of a fatty acid and the sulfhydryl group of CoA.
This activation reaction takes place on the outer mitochondrial membrane, where it is catalyzed by acyl CoA synthetase also called fatty acid thiokinase. Paul Berg showed that the activation of a fatty acid tymozcko accomplished in two steps. First, the fatty acid reacts with ATP to form an acyl adenylate. In this mixed anhydride, the carboxyl group tymocxko a fatty acid is bonded to the phosphoryl group of AMP. The other two phosphoryl groups of the ATP substrate are released as pyrophosphate.
These partial reactions are freely reversible. In fact, the equilibrium constant for the sum of these reactions tymoczio close to 1.
One high-transfer-potential compound is cleaved between PP i and AMP and one high-transfer-potential compound is formed the thioester acyl CoA.
How is the overall reaction driven forward? The answer is that pyrophosphate is rapidly hydrolyzed by a pyrophosphatase, and so the complete reaction is. This reaction is quite favorable because the equivalent of two molecules of ATP is hydrolyzed, whereas only one high-transfer-potential compound is formed.
We see here another example of a recurring theme in biochemistry: Another motif recurs in this activation reaction.
The enzyme-bound tymcozko intermediate is not unique to the synthesis of acyl CoA. Acyl adenylates are frequently formed when carboxyl groups are activated in biochemical reactions. Amino acids are activated for protein synthesis by a similar mechanism Section Thus, activation by adenylation recurs in part because of convergent evolution.
Fatty acids are activated on the outer mitochondrial membrane, boochemia they are oxidized in the mitochondrial matrix. A special transport mechanism is needed to carry long-chain acyl CoA molecules biofhemia the inner mitochondrial membrane. Activated long-chain fatty acids are transported across tymoczmo membrane by conjugating them to carnitinea zwitterionic alcohol. The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine.
This reaction is catalyzed by carnitine acyltransferase I also called carnitine palmitoyl transferase Iwhich is bound to the outer mitochondrial membrane. Acyl carnitine is then shuttled across the inner mitochondrial membrane by a translocase Figure The acyl group is transferred back to CoA on the matrix side of the membrane. This reaction, which is catalyzed by carnitine acyltransferase II carnitine palmitoyl transferase IIis simply the reverse of the reaction that takes place in the cytosol.
Normally, the transfer of an acyl group from an alcohol to a sulfhydryl group is thermodynamically unfavorable.
However, the equilibrium constant biochemua this reaction for carnitine is near 1, apparently because carnatine and its esters are solvated differently from most other alcohols and their esters because of the zwitterionic nature thmoczko carnitine. As a result, the O -acyl link in carnitine has a high group-transfer potential.
Finally, the translocase returns carnitine to the cytosolic side in exchange for an incoming acyl carnitine. The entry of acyl carnitine into the tymocz,o matrix is mediated by a translocase. Carnitine returns to the cytosolic side of the inner mitochondrial membrane in exchange for acyl carnitine.
A number of diseases have been traced to a deficiency of carnitine, the transferase or the translocase. The symptoms of carnitine deficiency range from mild muscle cramping to severe weakness and even death.
The muscle, kidney, and heart are the tissues primarily affected. Muscle weakness during prolonged exercise is an important characteristic of a deficiency of carnitine acyl transferases because muscle relies on fatty acids as a long-term source of energy. Medium-chain C 8 -C 10 fatty acids, which do not require carnitine to enter the mitochondria, are oxidized tgmoczko in these patients.
These diseases illustrate that the impaired flow of a metabolite from one compartment of a cell to another can lead to a pathological condition. A saturated acyl CoA is degraded by a recurring sequence of four reactions: Reaction Sequence for the Degradation of Fatty Acids. Fatty acids are degraded by the repetition of a four-reaction sequence consisting of oxidation, hydration, oxidation, and thiolysis. The first reaction in each round of degradation is the oxidation of acyl CoA by an acyl CoA dehydrogenase to give an enoyl CoA with a trans double bond between C -2 and C Electrons from the FADH 2 prosthetic group of the reduced acyl CoA dehydrogenase are transferred to a second flavoprotein called electron-transferring flavoprotein ETF.
Ubiquinone is thereby reduced to ubiquinol, which delivers its high-potential electrons to the second proton-pumping site of the respiratory chain Section The next step is the hydration of the double bond between C -2 and C-3 by enoyl CoA hydratase. The hydration of enoyl CoA is stereospecific. We shall return to this point shortly in considering how unsaturated fatty acids are oxidized. The hydration of enoyl CoA is a prelude to the second oxidation reaction, which converts the hydroxyl group at C -3 into a keto group and generates NADH.
This oxidation is catalyzed by l hydroxyacyl CoA dehydrogenasewhich is specific for the l isomer of the hydroxyacyl substrate. The preceding reactions have oxidized the methylene group at C -3 to a keto group.
The final step is the cleavage of 3-ketoacyl CoA by the thiol group of a second molecule of CoA, which yields acetyl CoA and an acyl CoA shortened by two carbon atoms. The shortened acyl CoA then tjmoczko another cycle of oxidation, starting with the reaction catalyzed by acyl CoA dehydrogenase Figure Fatty acyl chains containing from 12 to 18 carbon atoms are oxidized by the long-chain acyl CoA dehydrogenase.
The medium-chain acyl CoA dehydrogenase oxidizes fatty acyl chains having from 14 to 4 carbons, whereas the short-chain acyl CoA dehydrogenase acts only on 4- and 6- carbon acyl chains.
First Three Rounds in the Degradation of Palmitate. Two-carbon units are sequentially removed from the carboxyl end of the fatty acid. We can now calculate the energy yield derived from the oxidation of a fatty acid. Hence, the stoichiometry of oxidation of palmitoyl CoA is. Thus, the complete oxidation of a molecule of palmitate yields molecules of ATP.
By agreement with the publisher, this book is accessible by the search feature, but thmoczko be browsed. Turn recording back on. National Center for Biotechnology InformationU. W H Freeman; W H Freeman ; Triacylglycerols Are Hydrolyzed by Cyclic AMP-Regulated Lipases The initial event in the utilization of fat as an energy source is the hydrolysis of triacylglycerols by lipases, an event referred to as lipolysis.