Lipid Synthesis & Breakdown

Question 1

What is the substrate for lipogenesis and how does it leave the mitochondria?

Answer 1

Citrate from the TCA cycle leaves the mitochondria and is re-generated to acetylcoA in the cytoplasm

Question 2

AcetylcoA carboxylace (ACC)

Answer 2

Pathway: Lipogenesis

Rate limiting step of lipogenesis; converts acetylcoA to malonyl coA

MalonylcoA inhibits CPT-1 enzyme of lipolysis

Question 3

Fatty Acid Synthase

Answer 3

Pathway: Lipogenesis

Converts malonylcoA to palmitoyl coA; 3 palmitoyl coA molecules are jointed by glycerol to produce triacylglycerol

Requires NADPH from the HMP shunt pathway

Question 4

Hormone Sensitive Lipase

Answer 4

Pathway: Lipolysis

Cleaves FFAs from triglyeride in the cytosol

Fatty acids are transofmred to fatty acylcoA

Question 5

CPT-1

Answer 5

Pathway: Lipolysis

Converts fatty acyl coA molecules to acyl-carnitine; acyl-carnitine leaves the cytosol to enter the mitochondria, where it is regenerated into fatty acyl coA by loss of carnitine

Question 6

AcylcoA dehydrogenases

Answer 6

Pathway: Lipolysis

Convert fatty acyl coA to acetyl coA in the mitochondria; also produces NADH, FADH2, and a fatty acyl coA remnant which has been shortened by 2 carbons

Question 7

Fate of acetyl coA in lipolysis

Answer 7

AcetylcoA can enter the TCA cycle to generate NADH, FADH2, and GTP

Can be converted to ketones which leave the liver and diffuse to the brain for an alternative source of fuel under starvation conditions

Question 8

Ketogenesis

Answer 8

Pathway: Lipolysis

AcetylcoA produced by lipolysis is converted to a acetoacetylcoA, which is converted to HMGcoA by HMGcoA synthase; HMGcoA is cleaved by HMGcoA lyase to produce acetoacetate, which can be reduced to 3-hydroxybutyrate and acetone

Question 9

HMGcoA lyase

Answer 9

Pathway: Ketogenesis

Cleaves HMGcoA to acetoacetate; acetoacetate can be reduced to form 3-hydroxybutyrate and acetone

Question 10

Fate of fatty acyl remnants in lipolysis

Answer 10

Undergo repeated rounds of oxidation by fatty acyl dehydrogenase

Eventually, 3 carbon remnants (propionylcoA) undergo conversion through a methylmalonyl intermediate to succinylcoA, which enters the TCA cycle

Question 11

What is the effect of Vitamin B12 deficiency on lipolysis?

Answer 11

Vitamin B12 is required for conversion of 3 carbon fatty acyl remnants (propionylcoA) to succinyl coA

In Vitamin B12 deficiency, odd-numbered fatty acid intermediates (proprionate, methylmalonate) build up causing acidemia and are excreted in the urine, causing aciduria

The body relies more heavily on glucose as an energy source in the absence of lipolysis; predisposed to hypoglycemia