Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2
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Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2
23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2increased demand, such as exercise. During overnight fasting, fatty acids become rhe major fuel for cardiac muscle, skeletal muscle, and liver. The liver converts fatty acids to ketone bodies (acetoacetate and fi-hydroxybutyrate), which also serve as major fuels for tissues (e.g.. the gut). The brai Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2n, which does not have a significant capacity for fatty acid oxidation, can use ketone bodies as a fuel during prolongedfasting.The route of metabolisEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
m for a fatty acid depends somewhat on its chain length. Fart) acids are generally classified as very-long-chain length fatty acids /greater than C20)23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2 in the pathway of fl-oxidation Between meals and during overnight fasting, long-chain fatty acids are released from adipose tissue rrlacylgl) Carols They circulate through blood bound to albumin (Fig. 23. h. in cells, they are converted to fatty acyl CoA derivatives by acyl CoA synthetases The actu Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2ated acyl group is transported into the mitochondrial manix bound to carnitine, where fatty acyl CoA is regenerated. In the pathway of fl-oxidation. tEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
he fain- acyl group is sequentially oxidized to yield FAD(2H), NADU, and acetyl CoA. Subsequent oxidation ofNADH and FAD(2H) In the electron transport23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2e variations of this basic pattern. Long-chain fatly acids that are unsaturated fatty acids generally require additional isomerization and oxidation-reduction reactions to rearrange their double bonds during fl-oxidation. Metabolism of water-soluble medium-chain-length fatty acids does nor require c Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2arnitine and occurs only In liver. Odd-chain-length fatty acids undergo fl-oxidation to the terminal three-carbon propionyl CoA, which enters the TCAEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
cycle as succinyl CoA.Fatty acids that do not readily undergo mitochondrial fl-oxidation are oxidized first by alternate routes that convert them to m23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2cids that appear in urine. I'ery-long-chain fatty acids (both straight chain and branched fatty acids such as phytanic acid) are whittled down to size in peroxisomes Peroxisomal «- and fl-oxidiation generates hydrogen peroxide >HO:). NADH, acetyl CoA. or propionvl CoA and a short- to medium-chain-le Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2ngth acyl CoA. The acyl CoA products are transferred to mitochondria to complete their metabolism.In the liver, much of the acetyl CoA generated fromEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
fattv acid oxidation is converted to the ketone bodies, acetoacetale and fl-hydroxybutyra(e, which enter the blood (see Fig 23.1). In other tissues, t23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2c' ''-*NAOHKekxie boditJSQ Acetyl CoAtca\5^yl*'2CO2*NADH. FAD (2H). GTPFig. 23.1. Overview of tnitochondnal long-chain fatty acid metabolism (1) Fatty acid bindmg proteins (FaBP) transport fatly acids across the plasma membrane and bind them in thecytosol. (2) Fatty acyl CoA synthetase activates fat Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2ty acids to fatty acyl CoAs. (3 > Carnitine transports the activated fatty acyl group into mitochondria. <4) P-oxidation generates NADH. FaD<2H). andEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
acetyl CoA (5) In die liver, acetyl CoA is converted to ketone bodiesCoA. which is oxidized in the TCA cycle. The liver sy nthesizes ketone bodies but23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2 oxidative phosphorylation and ATP utilization. Additional regulation occurs through malonyl CoA. which inhibits formation of the fattv acyl carnitine derivatives. Fatty acids and ketone bodies are used as a fuel when their level increases In the blood, which Is determined by hormonal regulation of Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2adipose tissue lipolysis.® Cf) ®THE WAITING ROOM®Ot(0 Shape was disappointed that he did not place in his 5-kin race and has decided that short-distanEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
ce running IS probably not right for him. After carefill consideration, he decides to train for the marathon by running 12 miles tlưee times per week.23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2ietary supplements to increase his endurance and selects one containing carnitine. CoQ. pantothenate, riboflavin, and creatine.420 SECTION FOUR FUEL OXIDATION AND THE GENERATION OF ATPI.ofala Burnt is a 16-year-old girl. Since age 14 months she has experienced recurrent episodes ot profound fatigue Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2associated with vomiting and increased perspiration, which required hospitalization These episodes®The liver transaminases measured in the blood are aEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
spartate aminotransferase (AST), which was formerly called scrum glulam.-ilc oxaloacdale transaminase ISGOTI, and alanine: amino transferase (ALT), wh23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2tto’s distance running (a (/■’Ml moderate intensity exercise), dec reases in insulin and increases in insulin counterreợulatory hormones, such as epinephrine and norepinephrine, increase adipose tissue lipolysis. Thus, his muscles are being provided with a supply of fatty acids in the bluod that the Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2y can use as a fuel.z'T.ix Lofata Bume developed symptoms i pM) during fasting, when adipose tis-Kji' sue lipolysis was elevated. Under these circumstEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
ances, muscle tissue, liver, and many other tissues arc oxidizing (ally acids as a fuel. Alter overnight fasting, approximately 60 to 70% of our energ23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2ht and woke her early in the morning for breakfast. Lotata’s physical and mental development had progressed normally.On the day of admission for this episode, I.ofala had missed breakfast, and by noon she was extremely fatigued, nauseated, sweaty, and limp, she was unable to hold any food in her sto Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2mach and was lushed to the hospital, where an infusion of glucose was started intravenously. Iler symptoms responded dramatically to tillstherapy.HerEbook Marks’ basic medical biochemistry: A clinical approach - Part 2
initial scrum glucose level was low al 38 mg'dl. (reference range for fasling serum glucose levels 70 100). Iler blood urea nitrogen (BUN) level was s23 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of i Ebook Marks’ basic medical biochemistry: A clinical approach - Part 2nases were slightly elevated. although her liver was not palpably enlarged. Despite elevated levels of free fatty acids (4.3 mM) in the blood, blood ketone bodies were below normal. Ebook Marks’ basic medical biochemistry: A clinical approach - Part 223 Oxidation of Fatty Acids and Ketone BodiesFatty acids are a major fuel for humans and supply our energy needs between meals and during periods of iGọi ngay
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