Clinical diagnostic biochemistry - 6

Dr. Maha Al-Sedik2015

CLS 334

Lipids

Lipids are a class of hydrocarbon containing organic compounds.

Lipids are categorized by the facts that they are soluble in

nonpolar solvents (such as ether and chloroform) and are

relatively insoluble in water.

Lipids

They are major structural component of cell membranes.

It is a major source of fuel.

Dietary lipid is the only source for essential fatty acids.

4 vitamins D,E,A and k are associated with lipids.

Prostaglandin substances that stimulate smooth muscle

contraction and function in intracellular regulatory

process are lipid derivatives.

Functions of lipids:

Fatty acids:

General formula: R-COOH where R is alkyl chain of C and H.

Chemically, fatty acids can be described as long-chain

monocarboxylic acids and have a general structure of CH3(CH2)n

COOH. The length of the chain usually ranges from 12 to 24.

When the carbon chain contains no double bonds, it is called

saturated. If it contains one or more such bonds, it is unsaturated.

S t r u c t u r e o f f a t t y a c i d s

TRIGLYCERIDES

Lipases hydrolyze triacylglycerols, releasing 1 fatty acid at a time, yielding diacylglycerols & eventually glycerol.

Triacylglycerols (triglycerides) are the most abundant dietary lipids.

Each triacylglycerol has a glycerol backbone to which are esterified

3 fatty acids.

Most triacylglycerols are “mixed.” The 3 fatty acids differ in chain

length & number of double bonds.

Triglycerides are esters of glycerol and usually three different

fatty acids .

Constitute about 95% of adipose tissue and are the main form of

lipid storage in man .

Triglycerides are transported in plasma mostly in the form of

chylomicrons and VLDL.

The normal plasma range: below 200 mg/dl.

Increased in : • Hepatic disease.

• Nephrotic syndrome.

• Hypothyroidism.

• Diabetes mellitus.

• Pancreatitis .

• Pregnancy .

• Certain drugs (Oral contraceptives, corticosteroids and high dose

estrogens ) .

Normal <200

Borderline 200-400

High 400-1000

Very high >1000

Classification of triglycerides according to NCEP (National Cholesterol Educational Programme ) (mg/dl)

Triglycerides digestion and absorption

Most of dietary lipids are triglycerides, but small amount of

cholesterol and cholesterol esters are also ingested.

Fats require special digestive action before absorption ,because the

end products must be carried in a water medium (blood and

lymph) in which fats are not soluble.

It must be:

· Emulsified.

· Digested by hydrolytic enzymes.

· Absorbed into the intestinal mucosa.

1- Emulsification:Def: Breakdown of large fat molecules to tiny droplets called

micells which provide lipase with an increased surface to work on.

This action is initiated by :

Chewing action.

Gastric contraction.

Bile also help in emulsification.

The majority of dietary lipids are in a class called triacylglycerols

and are attacked by lipases to yield simple fatty acids and glycerol

molecules.

2- Digested by hydrolytic enzymes:

Lipase enzyme is attached to protein called co lipase .

Role of co - lipase :

• Prevent lipase from denaturation .

• Reverse the inhibitory effect of bile salts on lipase.

Lipases are enzymes produced by the liver, pancreas and stomach.

Gastric lipase: secreted by the stomach lining, has a pH value for

optimal activity around neutrality. It is essentially inactive in the

strongly acidic environment of the stomach. It is more important for

infant digestion since the gastric pH in infancy is much less acidic

than later in life.

Lipases

Pancreatic lipase: Most lipid digestion in the adult occurs in the

upper loop of the small intestine and is accomplished by a lipase

secreted by the pancreas, commonly referred to as pancreatic

lipase.

The end result is free fatty acids and a mixtures of mono- and

diacylglycerols.

Digestion and absorption of cholesterol: Emulsification by bile and chewing and stomach contraction.

Cholesterol esters are hydrolysed by pancreatic cholestryl

estrase into cholesterol and free fatty acids.

They are bound to the mixed micelles.

3- Absorbed into the intestinal mucosa: In the intestinal mucosa, beginning in the endoplasmic

reticulum and Golgi , the tri glycerides and cholesterol esters

acquire coating of protein ( Apo B 48 ) forming what is called

chylomicron.

Chylomicrons are transported into the blood and rapidly

disassembled and utilized through the body.

Fatty acids are absorbed by the apical microvilli of mucosal cells .

Apo B48 is the structural protein of the chylomicron.

Now the chylomicron is called Nascent chylomicron.

Then it reaches the blood where it has Apo C II and Apo E.

Apo C II stimulates lipoprotein lipase enzyme.

Lipoprotein lipase digest the triglyceride in the chylomicron

transforming chylomicron to chylomicron remnants.

Chylomicron remnants enter the hepatocyte by Apo E receptor in

the hepatocyte.

Reference: Burtis and Ashwood Saunders, Teitz fundamentals of Clinical Chemistry, 4th edition, 2000.

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