Lipogenesis & Lipolysis

Question 1

Hormone sensitive lipase (HSL)

Answer 1

Pathway: Lipolysis

Metabolizes triglycerides to free fatty acids within the adipocyte cytoplasm

HSL is activated by PKA under conditions of high glucagon; it is inhibited by dephosphorylation under conditions of high insulin

Question 2

Carnitine-palmitoyl transferae-1 (CPT-1)

Answer 2

Pathway: Lipolysis

Transfers the fatty acyl group from the fatty acid (liberated from TAG by HSL) to carnitine, forming acyl-carnitine; acyl-carnitine is transported from the adipocyte cytosol to the mitochondria

CPT-1 is inhibited by malonylcoA, an intermediate in lipogenesis

Question 3

Carnitine deficiency

Answer 3

Genetic carnitine deficiency results in massive triacylglycerol deposits in the liver

Presents with muscle cramping, hypoglycemia, and death

Question 4

Acyl coA Dehydrogenases

Answer 4

Catalyze oxidation of acyl coA molecules within the mitochondrial matrix; each round of oxidation shortens the original fatty acyl coA substrate by 2 carbons, produces acetyl coA, FADH2, and NADH

Question 5

Products of lipolysis

Answer 5

NADH and FADH2 - used to generate ATP

Acetyl coA - can enter the TCA cycle or be converted to ketone bodies

Question 6

How does Vitamin B12 deficiency affect lipolysis?

Answer 6

Vitamin B12 is required for enzymatic conversion propionylcoA (a 3 carbon fatty acyl coA remnant) to succinyl coA, via a methylmalonyl intermediate

Vitamin B12 deficiency causes accumulation of propionylcoA and methylmalonyl coA, which build up in the blood causing metabolic acidosis and in the urine causing aciduria; additionally, these patients cannot make full use of TAGs as an energy source and rely more heavily on glucose; they are at-risk for hypoglycemia

Question 7

Acyl coA Dehydrogenase deficiencies

Answer 7

Pathway: Lipolysis

Medium chain dehydrogenase deficiency is most common

Characterized by hypoglycemia, increased urinary excretion of carnitine esters with low tissue carnitine levels, low levels of ketone bodies in fasting state

Treated with a low fat, high carbohydrate diet

Question 8

HMGcoA Synthase

Answer 8

Pathway: Ketone body production

Catalyzes production of HMGcoA from acetoacetylcoA and acetylcoA in the mitochondria of hepatocytes

Question 9

HMGcoA Lyase

Answer 9

Pathway: Ketone body production

Catalyzes the breakdown of HMGcoA to acetoacetate and acetylcoA

Acetoacetate can be reduced to 3-hydroxybutyrate by NADH or can decarboxylate to form acetone; 3-hydroxybutyrate diffuses to muscle and brain where it is re-generated to acetylcoA to enter the TCA cycle