1. Ketone body metabolism ط Ketogenesis, Site and steps ط Ketolysis, sites and steps for utilization ط Regulation of ketogenesis and ketolysis ط Starvation and ketosis ط Clinical correlation Ketoacidosis D4 387-91

2. KB Synthesis (only in liver Mitoch) KB are water-soluble lipid-base energy (AcetoAcetate=> reduced => β- Hydroxybutarate) fig.9.24, ACoA + ACoA  KT-lase  AACoA AACoA + ACoA  HMGCoA S-ase (+CoA)  HMGCoA HMGCoA  HMGCoA Lyase (+CoA)  Acetoacetate + ACoA Acetoacetate => acetone + CO 2  AADH (–NADH)  d- β -Hydroxybutarate

3. KB Utilization KB is used by extrahepatic tissues (cardiac& skeletal muscles / CNS) Acetoacetate + SCoA  AA:SCoA T-ase  AACoA + Succinate AACoA  KetoThiolase (–CoA)  Acetate => TCA cycle Succinate => TCA cycle AACoA  AA KT  Acetoacetate

4. Importance of KB 1. Conserve Glu for CNS support 2. Uptake by brain for further conservation 3. In Diabetes, Hormonal control for Glu conservation (Ketosis)

5. Clinical Correlation of KB · Rufsum’s Disease cc.9.6 o Phytanic Acid (milk lipid, animal fat) ==X=stop ==> no α-oxid => 3 PCoA + 3 ACoA + 1 IsobutyrylCoA o Lack of a-hydroxylation enzyme lead to accumulation of Phytanic Acid causing neurological problems - Retinitis pigmentation / peripheral neurophathy / cerebellar ataxia / nerve deafness o Treat by restriction of dietary dairy & meat products · Ketoacidosis cc.9.7 o Diabetic ketoacidosis is common with NIDM o Ketosis is triggered by INS deficiency / GLG Excess + Elevated Epineph, cortisol, GH o Hyperglycemia, Ketonemia, Ketonuria (metabolic acidosis) o Decrease in INS does not restrain FA to liver leading to high plasma FA causing high hepatic ketone production o Treated with INS