Lipid Mobilization and Catabolism

Question 1

T/F: Adipose tissue initiates lipid catabolism as a response to glucagon.

Answer 1

False. Hormon-sensitive triacylglycerol lipase (HSL) responds to the “fall in insulin” rather than glucagon. Epinephrine and cortisol also activate HSL

Question 2

MOA of Niacin as an antihyperlipidemic drug

Answer 2

In large doses (gram-level), Niacin inhibits HSL

Question 3

Fate of glycerol from the breakdown of TAGs in adipose

Answer 3

Enters liver to provide carbon backbone for Gluconeogenesis

Question 4

Activators of HSL

Answer 4

Decreased Insulin, Increased Epinephrine, Induced by Cortisol

Question 5

Rate limiting enzyme in long-chain fatty acid oxidation

Answer 5

Carnetine acetyltransferases (CAT)/Carnitine palmitoyl transferases (CPT)

Question 6

Activation of fatty acid (addition of CoA group) catalyzed by

Answer 6

Fatty Acyl-CoA synthetase (consumes 1 ATP) in outer mitochondrial membrane to generate FA-CoA

Question 7

CAT/CPT inhibited by

Answer 7

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)

Question 8

Products of 1 round of Beta-oxidation

Answer 8

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)

Question 9

Profound fasting hypoglycemia yet low to absent ketones, C8-C10 Acyl carnitines in blood

Answer 9

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

Question 10

Myalgia, rhabdomyolysis, myoglobinuria, red urine, episode provoked by prolonged exercise, fasting, cold stress, Muscle biopsy shows elevated muscle triglyceride (lipid droplets in cytoplasm)

Answer 10

Carnitine Acyltransferase-2 CAT-2/CPT-2 Deficiency (Myopathic Form, adolescent or adult onset)

Question 11

Intermediates of the Propionic Acid Pathway

Answer 11

Propionyl CoA (the 3-C FA-CoA from beta-oxidation) > Methylmalonyl-CoA > Succinyl CoA (to Krebs)

Question 12

Methylmalonic aciduria is caused by what vitamin deficiency

Answer 12

Vit B12 (cobalamin). It is required by Methylmalonyl-CoA Mutase to convert Methylmalonyl- to Succinyl CoA

Question 13

Ketone utilized by the brain

Answer 13

Beta-hydroxybutyrate

Question 14

Ketogenesis occurs where

Answer 14

Mitochondria

Question 15

Enzyme lacking in the liver, making it unable to utilize ketone bodies as an energy source

Answer 15

Thiophorase (Succinyl-CoA acetoacetyl-CoA transferase), converts Acetoacetate to Acetoacetyl-CoA (which is split to form 2 Acetyl-CoAs)

Question 16

Ceramide modifications (addition of hydrophilic groups) to yield Sphingolipids

Answer 16

Phosphatidylcholine: Sphingomyelin, Galactose/glucose: Cerebrosides, Oligosaccharides + Sialic acid: Gangliosides

Question 17

Cherry red spots in macula, blindness, Psychomotor retardation, Death < 2yrs, Startle reflex, Ashkenazi Jews, AR

Answer 17

Tay-Sachs disease

Question 18

Cherry red spots in macula, hepatosplenomegaly, microcephaly, Zebra bodies, foamy macrophages, early death, AR

Answer 18

Niemann-Pick disease

Question 19

Enzyme deficiency in Tay Sachs

Answer 19

Hexosaminidase A (accumulation of Ganglioside GM2)

Question 20

Enzyme deficiency in Niemann Pick

Answer 20

Sphingomyelinase (accumulation of Sphingomyelinase)

Question 21

Crumpled paper inclusions. Erosion of bones/fractures, pancytopenia, Type 1: Adult hepatosplenomegaly, Ashkenazi Jews, AR

Answer 21

Gaucher disease

Question 22

Enzyme deficiency in Gaucher

Answer 22

Glucocerebrosidase (Glucocerebroside)

Question 23

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

Answer 23

Fabry Disease

Question 24

Important enzymes in Ketogenesis (occuring in the Mitochondrial Matrix

Answer 24

HMG-CoA Synthase, HMG-CoA Lyase