Lipid Mobilization and Catabolism Flashcards
T/F: Adipose tissue initiates lipid catabolism as a response to glucagon.
False. Hormon-sensitive triacylglycerol lipase (HSL) responds to the “fall in insulin” rather than glucagon. Epinephrine and cortisol also activate HSL
MOA of Niacin as an antihyperlipidemic drug
In large doses (gram-level), Niacin inhibits HSL
Fate of glycerol from the breakdown of TAGs in adipose
Enters liver to provide carbon backbone for Gluconeogenesis
Activators of HSL
Decreased Insulin, Increased Epinephrine, Induced by Cortisol
Rate limiting enzyme in long-chain fatty acid oxidation
Carnetine acetyltransferases (CAT)/Carnitine palmitoyl transferases (CPT)
Activation of fatty acid (addition of CoA group) catalyzed by
Fatty Acyl-CoA synthetase (consumes 1 ATP) in outer mitochondrial membrane to generate FA-CoA
CAT/CPT inhibited by
Malonyl CoA from Fatty Acid synthesis (prevents newly synthesized Fas from entering the mitochondria for oxidation, making FA synthesis pointless), and Insulin (indirectly via activation of acetyl-CoA carboxylase/fatty acid synthesis/malonyl CoA concentration in cytoplasm)
Products of 1 round of Beta-oxidation
1 Acetyl CoA, 1 NADH, 1 FADH2 (Acetyl CoA can be used for Ketogenesis or Gluconeogenesis by Liver, or Additional energy via Krebs by the Muscles)
Profound fasting hypoglycemia yet low to absent ketones, C8-C10 Acyl carnitines in blood
Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency; Tx: IV glucose; Prevent hypoglycemia, exercise, infections; May be provoked by an overnight fast in an infant and cause SIDS
Myalgia, rhabdomyolysis, myoglobinuria, red urine, episode provoked by prolonged exercise, fasting, cold stress, Muscle biopsy shows elevated muscle triglyceride (lipid droplets in cytoplasm)
Carnitine Acyltransferase-2 CAT-2/CPT-2 Deficiency (Myopathic Form, adolescent or adult onset)
Intermediates of the Propionic Acid Pathway
Propionyl CoA (the 3-C FA-CoA from beta-oxidation) > Methylmalonyl-CoA > Succinyl CoA (to Krebs)
Methylmalonic aciduria is caused by what vitamin deficiency
Vit B12 (cobalamin). It is required by Methylmalonyl-CoA Mutase to convert Methylmalonyl- to Succinyl CoA
Ketone utilized by the brain
Beta-hydroxybutyrate
Ketogenesis occurs where
Mitochondria
Enzyme lacking in the liver, making it unable to utilize ketone bodies as an energy source
Thiophorase (Succinyl-CoA acetoacetyl-CoA transferase), converts Acetoacetate to Acetoacetyl-CoA (which is split to form 2 Acetyl-CoAs)
Ceramide modifications (addition of hydrophilic groups) to yield Sphingolipids
Phosphatidylcholine: Sphingomyelin, Galactose/glucose: Cerebrosides, Oligosaccharides + Sialic acid: Gangliosides
Cherry red spots in macula, blindness, Psychomotor retardation, Death < 2yrs, Startle reflex, Ashkenazi Jews, AR
Tay-Sachs disease
Cherry red spots in macula, hepatosplenomegaly, microcephaly, Zebra bodies, foamy macrophages, early death, AR
Niemann-Pick disease
Enzyme deficiency in Tay Sachs
Hexosaminidase A (accumulation of Ganglioside GM2)
Enzyme deficiency in Niemann Pick
Sphingomyelinase (accumulation of Sphingomyelinase)
Crumpled paper inclusions. Erosion of bones/fractures, pancytopenia, Type 1: Adult hepatosplenomegaly, Ashkenazi Jews, AR
Gaucher disease
Enzyme deficiency in Gaucher
Glucocerebrosidase (Glucocerebroside)
X-linked sphingolipidosis, A-galactosidase A (A-Gal-A) enzyme deficiency, Angiokeratomas, Burning sensations in the hands, Cloudiness of cornea, Renal failure often cause of death
Fabry Disease
Important enzymes in Ketogenesis (occuring in the Mitochondrial Matrix
HMG-CoA Synthase, HMG-CoA Lyase
