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
FADL – An E. coli Fatty Acid Transporter 1)b-Barrel Transmembrane Protein 2)14 Antiparallel b-sheets 3)N-terminal “hatch” domain 4)Conformational change on substrate binding opens hatch a)Ribbon drawing of intact protein b)“Hatch” domain c)Cutaway view to show hatch in central channel d)Cytoplasmic space-filling view to show hatch plugging channel van den Berg, B. (2005) Current Opinion in Structural Biology 15(4): 401-407.
Fate of Glycerol Not wasted Shuttled to liver in blood Catabolized there Glycolysis Gluconeogenesis
Pernicious Anemia B12 is produced only by several genera of bacteria, obtained from animal food daily requirement is about 2-3 g/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.)
Peroxisomes -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)
Catalase Glucose Acyl CoA Dehydrogenase Acyl CoA Oxidase
Catalases Once again, a heme-containing enzyme Overall reaction: 2 H 2 O 2 ⇄ O 2 + 2 H 2 O First step: produces porphyrin cation radical Second step: HOOH acts as electron donor to produce O 2 and return enzyme to resting state.
Catalase is a fun enzyme to assay Mr. Bubble of the enzyme world Staphylococcus aureus
Plants don’t store much fat, but seeds often do.
Refsum’s Disease Phytanoyl CoA Hydroxylase deficiency Can also digest phytanic acid by -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
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.
Diabetic Ketoacidosis Primarily in Type 1 (insulin-dependent) Low insulin = low glucose transport into cells Liver thinks it’s starving Ketone body production ramps up Blood pH drops into danger zone