Lipid Mobilization and Catabolism

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Fatty acid oxidation:

• Oxidized in liver, muscle, adipose tissue.

• Pathway used is beta-oxidation; even C-number of fatty acids yield 2 acetyl CoA; odd C-number of fatty acids yield 1 acetyl CoA and 1 propionyl-CoA.

• Fatty acids transported into mitochondria by carnitine acyltransferase-1 and other systems.

• Carnitine acyltransferase-1 is inhibited by malonyl-CoA.

• Insulin inhibits beta-oxidation by increasing malonyl-CoA.

• Glucagon opposes insulin.

Beta-oxidation of fatty acids in mitochondria produces: NADH and FADH2.

• NADH and FADH2 sent to ETC to produce ATP.

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency:

• Defective fatty acid metabolism.

• Blocked hepatic beta-oxidation of fatty acids, causing hypoglycemia.

• Lethargy, coma, death.

• Acidemia.

• Provoked by fasting.

• May cause SIDS in babies.

Treatment:

• IV glucose.

Prevention:

• Frequent feeding, high carbohydrate and low fat diet.

Propionic Acid Pathway:

• Propionyl-CoA created during odd C-containing fatty acid beta-oxidation is digested, i.e., converted to succinyl-CoA.

Ketogenesis:

• Occurs in mitochondria of hepatocytes when access acetyl-CoA accumulates.

• One byproduct is acetone.

Ketoacidosis:

• Ketone synthesis exceeds metabolism.

• Excess acetone; fruity breath.

• Precipitated by infection or trauma.

• Seen in type 1 insulin-dependent diabetes mellitus, alcoholics.

• Findings: thirst, dehydration, CNS depression, coma, decreased bicarbonate.

Sphingolipids:

• Constituents of cell membranes.

• Three main classes: sphingomyelin, cerebrosides, and gangliosides.

• Sphingolopids are digested in endosomes after fusion with lysosomes.

• Defective lysosomes cannot fully digest sphingolipids, causing accumulations within cells.

• Diseases: Tay-Sachs, Gaucher, and Niemann-Pick.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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