1 / 62

Lipid Catabolism

Lipid Catabolism. CH339K. Fats are stored in lipid droplets. Lipid droplets in a rat adipocyte. Glucagon Epinephrine. Human Serum Albumin. 30-50 g/l of blood 67 kDal 585 amino acids Can bind up to 10 fatty acids Different binding sites have different affinities

newton
Télécharger la présentation

Lipid Catabolism

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lipid Catabolism CH339K

  2. Fats are stored in lipid droplets Lipid droplets in a rat adipocyte

  3. Glucagon Epinephrine

  4. Human Serum Albumin • 30-50 g/l of blood • 67 kDal • 585 amino acids • Can bind up to 10 fatty acids • Different binding sites have different affinities • Also binds thyroid hormones

  5. FADL – An E. coli Fatty Acid Transporter b-Barrel Transmembrane Protein 14 Antiparallel b-sheets N-terminal “hatch” domain Conformational change on substrate binding opens hatch Ribbon drawing of intact protein “Hatch” domain Cutaway view to show hatch in central channel Cytoplasmic space-filling view to show hatch plugging channel van den Berg, B. (2005) Current Opinion in Structural Biology 15(4): 401-407.

  6. Fate of Glycerol • Not wasted • Shuttled to liver in blood • Catabolized there Glycolysis Gluconeogenesis

  7. Activation of Fatty Acids Overall: Keq = 535,000 Keq = 1589 Keq = 337

  8. Transport into the Mitochondrion (Carnitine-Acylcarnitine Translocase)

  9. b-oxidation • Mitochondrial matrix • Oxidizes fatty acyl CoA’s at the b carbon • Sequentially cleaves off acetyl CoAs • Acetyl CoA is processed through Krebs and ETC

  10. 2 Systems for b-oxidation • ≥ 12 carbons: • TFP – last 3 enzymes in multienzyme complex • < 12 carbons • 4 soluble matrix enzymes

  11. Palmitate weighs ~256 g/mol (about 42% more than glucose) • Oxidation yields 108 ATPs, versus 32ish for glucose (about 340% more)

  12. Monounstaurated • Fatty Acids • Need one extra enzyme • Converts double bond 1

  13. Polyunsaturated Fatty Acids • Need two extra enzymes • Reduce conjugated double bonds to a single double bond 1 2 1

  14. Odd-numbered Fatty Acids • Left with 3 carbons • Add inorganic carbon • Convert to succinate • Throw into Krebs Cycle

  15. Pernicious Anemia • B12 is produced only by several genera of bacteria, obtained from animal food • daily requirement is about 2-3 mg/day • Gastric mucosa produces a protein called intrinsic factor • Lack of intrinsic factor results in impaired B12 absorption, pernicious anemia, death in 1-3 years • Original treatment (1920’s) was ½ lb. of raw liver daily • Concentrated liver juice (yum) became available in 1928 • B12 isolated in 1948, synthesized in 1973 • Now treated with large doses (several mg) B12 • Sources: fish, meat, poultry, eggs, milk, especially liver and mollusks (clams, oysters, etc.)

  16. Liver Juice! Ummm!!!

  17. Regulation (ACC = Acetyl CoA Carboxylase)

  18. Peroxisomes • b-Oxidation also occurs in peroxisomes (major site in plants) • In critters, peroxisomes are primary organelles for oxidation of very long chain and branched fatty acids (cerotic acid, phytanic acids)

  19. Acyl CoA Oxidase Acyl CoA Dehydrogenase Catalase Glucose

  20. Catalases • Once again, a heme-containing enzyme • Overall reaction: 2 H2O2⇄ O2 + 2 H2O • First step: produces porphyrin cation radical • Second step: HOOH acts as electron donor to produce O2 and return enzyme to resting state.

  21. Catalase is a fun enzyme to assay • Mr. Bubble of the enzyme world Staphylococcus aureus

  22. Plants don’t store much fat, but seeds often do.

  23. Ω-Oxidation • ER of vertebrates • Medium chain FAs

  24. a-oxidation Herbivores consume a lot of chlorophyll. Chlorophylls have a long hydrophobic tail. Those tails are split off as part of digestion to form phytanates.

  25. a-oxidation • (Peroxisomes) • Phytanates have b-methylgroups • Can’t do b-oxidation • Dietary phytanates • Dairy • Fish • Animal fats

  26. Refsum’s Disease • Phytanoyl CoA Hydroxylase deficiency • Can also digest phytanic acid by w-oxidation, but only ~10 mg/day • Typical diet contains 50 mg • Builds up in myelin sheath • Also screws up vitamin A metabolism • Demyelinating neuropathy, cerebellar ataxia, deafness, anosmia, cranial nerve degeneration

  27. Refsum’s sign

  28. Ketone Body Generation • During fasting or carbohydrate starvation, oxaloacetate in the liver is used for gluconeogenesis. • Acetyl-CoA then doesn’t enter Krebs cycle. • Acetyl-CoA converted in mitochondria to ketone bodies, • Ketone bodies are transported in the blood to other cells • Converted back to acetyl-CoA for catabolism in Krebs cycle, to generate ATP.

More Related