Lipid Metabolism II

pt. II

3 pathways of lipid metabolism

exogenous - dietary

endogenous - liver derrived

reverse cholesterol transport

Exogenous pathway

focused on dietary fat absorption w/i intestines

Endogenous pathway

focused on lipid synthesis in the liver

Reverse cholesterol transport

focused on returning cholesterol from tissues back to the liver to be processed

Exogenous pathway absorbs

Dietary lipids forming chylomicrons - CM, ULDL

Chylomicron (CM)

travel lymphatic system and enter bloodstream

Lipoprotein Lipase (LPL)

utilized in adipose and muscle tissue; breaks down triglycerides from CM to release FA for storage or energy

What is the goal of the endogenous pathway?

synthesize triglycerides & package into VLDL > TGS is released and becomes IDL > IDL metabolized into LDL to deliver cholesterol

RCT pathway

cholesterol picked up from peripheral tissue via HDL > sent back to liver to be excreted as bile acids

What mediates the endocytosis of whole LPs

lipoprotein receoptors

Hepatic lipase (HL)

modulates the bindng of lipoproteins to receptors or stimulate the uptake via selective transporters

Where does de novo synthesis occur?

cytoplasm

Where does catabolism occur?

mitochondriaW

What does catabolism of FA produce?

Acetyl CoA - to be sent to Kreb’s cycle

How are FA converted to acetyl groups?

b-oxidation

What is the rate limiting step of lipid metabolism?

Carnitine palmitoyl transferase (CPT1)

What occurs during B-oxidation?

2 carbon compounds are lost

B-Oxidation cycle

oxidate > hydration > oxidation > cleavage

How much energy is generated during b-oxidation?

1 FADH2

1 NADH

1 A-CoA

How much energy is produced by an 18-C FA?

8 FADH

8 NADH

9 A-CoA

How much ATP is equal to 1 FADH

1.5ATP

How much ATP is equal to 1 NADH

2.5 ATP

How much ATP is equal to 1 A-CoA

10 ATP

Clinical considerations for lipid metabolism

Lipemia, hyperlipidemia, hepatic lipidosis, ketosis, obesity

Hyperlipidemia

increased conc. of lipids in the blood

postprandial or pathological

serum will appear milky

Lipemia

turbid/lactescent appearance of serum or plasma due to hypertyriglyceridemia

Hypertriglyceridemia

most severe form of hyperlipidemia

TGS >200 mg/dl in dogs

Hepatic lipidosis

AKA fatty liver

in feline caused by too much mobilized stored fat

in dairy cows caused by transition from pregnancy to lactation 

in bearded dragons there’s a 38% occurrence in necropsy

Chylomicrons form in refrigerated blood samples because?

low density causes them to float to the top

When are ketone bodies formed?

following excess lipolysis; can be used to generate energy in most aerobic tissues

Where can KB’s not generate energy?

the liver

Metabolic function of Ketone bodies

freely circulating lipids; ensure sufficient levels of FA for aerobic resp.

if ATP is sufficient, A-CoA channeled to alt. pathway > ketone bodies

Ketosis

High levels of ketone bodies within the liver

Ketoacidosis

ketone bodies cause blood pH to fall

Why is ketosis uncommon in equine?

Ketone formation less developed, greater capacity to export VLDL from hepatocyes

Ruminants are prone to

fatty liver infiltration - steatosis, fatty liver