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Overview Lipid Metabolism Regulation

RB MYBURG 2011

Objectives
Lipid transport Enzymes involved in lipid metabolism Describe synthesis and degradation of fatty acids and cholesterol
Regulatory steps Hormone-sensitive lipase

Plasma Lipoproteins

Major functions of lipoproteins


Apoprotein
Chylomicrons Apo-A, Apo-B48, Apo-CII, Apo-E VLDL Apo-B100, Apo-CII, Apo-E

Functions
Triacylglycerols from gut

Triacylglycerols from liver to adipose tissue Enriched in cholesteryl esters Deliver cholesterol to extra-hepatic tissue Scavenges cholesterol as it circulates in blood

LDL

Apo-B100

HDL

Apo-A, Apo-C, Apo-E

Enzymes involved in lipid metabolism


Lipoprotein lipase
Capillary walls Activated by Apo-CII Deficiency Apo-CII, LPL Homozygous Heterozygous

Hepatic triglyceride lipase


Removes TG from IDL Deficiency chylomicron & VLDL remnants

LCAT
Apo-AI Deficiency CE & HDL

Cholesteryl ester transfer protein (CETP)


Associated with HDL in circulation Exchanges of cholesteryl esters from HDL with TAG from chylomicrons/VLDL

Phospholipid transfer protein (PLTP)


Provides phospholipids to HDL Mature HDL depends on PLTP

Hormone-sensitive lipase
Intracellular neutral lipase

Hydrolyses esters
Long form steroidogenic tissues cholesteryl ester hydrolase Short form adipose tissue triglyceride lipase

Activation
Phosphorylation of perilipin A Hormonal catecholamine ACTH insulin glucagon

Fatty acids : Synthesis & Oxidation

Regulation of -oxidation
NO DIRECT REGULATION
Malonyl CoA inhibition of CPT I Hormone-sensitive lipase

Regulation of -oxidation - HSL

Regulation of Synthesis
Acetyl CoA carboxylase Most active state = polymer comprising 3 or more nonphosphorylated monomers Allosteric binding of citrate lipogenesis Allosteric binding of palmitate lipogenesis Hormonal regulation glucagon, epinephrine, insulin, AMP

Regulation of Synthesis

Regulation of Synthesis

Acetyl CoA

Bile acids

Steroid hormones

Storage

Transport Membranes

O || R-C-O

Cholesterol synthesis
Acetyl CoA + Acetoacetyl CoA HMG CoA
HMG CoA reductase

Mevalonate Farnesyl pyrophosphate Squalene

Cholesterol

Regulation of HMG CoA Reductase

Regulation of HMG CoA Reductase : Cholesterol

Regulation of HMG CoA Reductase : Hormonal

Hormone-sensitive lipase

Functions of Hormones Derived from Cholesterol


Product Progesterone Glucocorticoids (cortisol) (produced in adrenal cortex) (catabolic steroid) Mineralocorticoids (aldosterone) (produced in adrenal glands) Functions prepares uterus lining for implantation of ovum promote gluconeogenesis; favor breakdown of fat and protein (fuel mobilization); anti-inflammatory maintains blood volume and blood pressure by increasing sodium reabsorption by kidney

Functions of Hormones Derived from Cholesterol


Product
Androgens (strongest = testosterone) (produced in testes primarily but weak androgens in adrenal cortex) (anabolic steroid)

Functions
development of male secondary sex characteristics; prevents bone resorption

Estrogen development of female (produced in ovaries primarily but also secondary sex in adipose cells of males and females) characteristics; prevents bone resorption Vitamin D (not a steroid hormone) (produced in the skin in response to UV light and processed to active form in kidney) intestinal calcium absorption; promotes bone formation; prevents phosphate loss by kidneys

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