plasma lipids 1- in mammals, principal lipids that have metabolic

8/14/2019 PLASMA LIPIDS 1- In Mammals, Principal Lipids That Have Metabolic

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PLASMA LIPIDS1- In mammals, principal Lipids that have metabolic significance are as follows:

Triacyl glycerol (TG): also called Neutral fats (NF)

Phospholipids and

Steroids: chief of which is cholesterol.

Plasma lipids also constitute the products of the metabolism.

Fatty acids: long-chain and short-chain (free FA) and Glycerol.

2-Extraction of plasma lipids with a suitable Lipid solvent and subsequent separation of the extract

into various classes of lipids shows the presence of:

Triacyl glycerol (TG)

Phospholipids (PL) Approximately in equal quantities

Cholesterol and

A much smaller fraction of non-esterified long-chain fatty acid (NEFA) or free-fatty acid (FFA),

which constitutes less than 5% of total FA present in plasma.

3-NEFA is now known to be metabolically most active of the plasma lipidsand life being 2-3minutes.4- Plasma lipids at any time may be considered to represent the net balance between production,

utilization and storage.

Table showing lipid fractions in plasma

Lipid fractions Plasma level in mg/100ml

Range Mean

Total lipids 360-820 560

Triacyl glycerol (TG) 80-180 150

Total Phospholipids (PL) 125-390 210

Phosphatidyl choline

(lecithin)

50-200

Phosphatidyl ethanolamine(cephalin)

50-130

Sphingomyelins 15-35

Total cholesterol 150-250 200

Free cholesterol (nonesterified) 25-105 55

Free fatty acids or nonesterifiedFA(NEFA)

6-16 10

TRANSPORTATION OF PLASMA LIPIDSPrincipal Lipid, triacyl glycerol (TG), is hydrophobic material. To transport them in blood in an

aqueous medium poses a problem, which is solved by associating more insoluble lipids with more

"Polar" ones, such as phospholipids, cholesterol and combining with a specific, protein molecule

(called as 'apo-proteins')- Thus, the hydrophobic and insoluble triacyl glycerol (TG) is converted by

above combination into a hydrophilic and "soluble" Lipoprotein "complex".

Thus:


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TG derived from intestinal absorption of fats are transported in the blood as a lipoprotein complex

called "chylomicrons". Chylomicrons are small microscopic particles of fats, about 1u in diameter and

are responsible for transport of exogenous (TG) in the blood.

Similarly, TG that are synthesized in Liver cells are converted to lipoprotein particles, called "very

low density lipoproteins" (VLDL) and thrown into the circulation. VLDL is mainly concerned with

transport of endogenous TG.

In addition to above, Fatty acids released from adipose tissue by hydrolysis of TG are thrown in the circulation as free

fatty acid (FFA). They are carried in non-esterified state in plasma hence also called NEFA. In

circulation, FFA/ NEFA combines with albumin and are carried as "albumin-FFA complex". Some 25

to 30 mols of FFA are present in combination with one mol. of albumin.SEPARATION OF PLASMA LIPIDS

(a) Ultracentrifugation: Pure fat is less dense than water. As the proportion of lipid to protein in

lipoprotein complex increases the density of the molecule decreases. This property has been utilized in

separation of plasma lipids, the various lipoprotein fractions, by ultracentrifugation.

Sf Unit: The rate at which each lipoprotein fraction floats up through a solution of NaCl (Sp. gr =

1.063) is expressed in "Svedberg units" (Sf units). One Sf unit is equal to 10r13 cm/sec/dyne/gm at

26C.

Because of the low densities, the chylomicrons and VLDL rise to the surface most rapidly upon

ultracentrifugation and hence have relatively high Sf values. Composition of various Lipoproteinfractions separated by ultracentrifugation is given in Table 21.2.

(b) Electrophoresis: Lipoproteins may be separated also according to their electrophoretic properties

and identified more accurately using immunoelectro-phoresis. Fredrickson and others (1967)

identified lipoproteins into 4 groups by electrophoresis as follows:

HDL: moves fastest and occupies position of a globulin-called a lipoproteins

LDL: -lipoproteins VLDL: (Pre- or 2 lipoproteins) and Chylomicrons: slowest moving and remains near the origin.

Composition of lipoprotein complexes and apoproteins (Refer, Lipoproteins metabolism)

Table 21.3 shows the normal value of Lipoprotein fractions in health.METABOLISM OF ADIPOSETISSUE

The lipids in the body physiologically exist in two forms:

"Element constant" or structural lipids and

"Element variable": stored lipids (Depot fats).

Although a sharpline of demarcation cannot be made between the two, it has been generally observed

that the value of the former remains constant even under extremes of starvation, whereas the latter


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varies. Composition of Element Constant: Cytoplasm and cell membranes of all organs are

composed of"element constant", so that their fat content does not diminish in starvation. Element

constant is composed chiefly of Phospholipids (PL), along with smaller amounts of other lipids,

including cholesterol. It is independant of previous feeding. It remains an integral part of cellprotoplasm and is essential for its life.

Composition of Element Variable: The lipids which is stored in the body in excess of above. The

amount fluctuates and it is composed mainly of triacyl glycerol (TG), also called as neutral fats (NF).

Thus depot fat is chiefly composed of glycerides of various fatty acids and usually contains 75% of

oleic acid, 20% of palmitic acid and 5% of stearic acid. Traces of lecithin and cholesterol as well as a

little amount of Polyunsaturated FA are also present. The depot fat is called "adipose tissue", they are

intracelhilar fats which remain inside the cells of adipose tissue.TABLE 21.3: NORMAL VALUES OF LIPOPROT (NORMAL LIPID PROFILE)

Lipid fractionNormal valueTotal cholesterolSerum HDLcholesterolSerum TG (Triacyl glycerol) Serum chylomicrons

Serum pre-p lipoproteins (VLDL) Serum p-lipoproteins (LDL) "Serum LDLcholesterol150 to 240 mg/d males35 to 60 female40 to 7C males60 to 16! females40 to 1 up to 28 mg/dli post-absorptive males

up to 24 femalesup to', up to 550 mg/d

up to 190 mg/d"Serum LDLcholesterol can be calculated by the Friedeii LDLcholesterol in mg/dl =T/"1

Total cholesterolHDL cholesterol - LDLcholesterol in m.mol/L =TG

Total cholesterolHDL cholesterol -Note: The formula is not much reliable at TG co > 4.5 m. mol/L (> 400 mg/dl).


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Dynamic State of Adipose Tissue: Adipose t just a static lump of fats; it is in "dynanbreakdown of

fats and synthesis take place aMETABOLISM

TG stores in the body is continually und acts on acetic acid and :acid


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Iwifdium chain synthetase - acts on FA with igth C4 to C12JIMacyl-CoA synthetase ~^> Acts on FA with gth C8 to C22a GTP-specific mitochondrial acyl-CoA ase described which forms GDP + Pi! AND ITS ROLE IN FA METABOLISM

L (acyl-CoA) are formed in cytosol, whereas i of FA occurs in mitochondrial matrix.Acyl neable

to mitochondrial membrane. Long-ited FA penetrate the inner mitochondrial eonly in

combination with carnitine.tChemistry and functions: s chemically "p-OH-y-trimethyl ammoniumHistorical background:Fraenk^l's vitamin BT is same as carnitine. It was found to be required as a nutritional factor in

meal-worm (Tenebrio molitor). If the meal worms are fed on a synthetic diet, deficient in vitamin

BT they die in 4 to 5 weeks.

Distribution: Carnitine is widely distributed in yeast, milk, liver and particularly large quantitiesin muscles and in meat extracts.

Concentration: Fraenkel used bio-assay technique based on the rate of growth of larvae ofTenebrio molitor and found that in mammals, carnitine content of:

Skeletal muscle: 1 mg/Gm dry weight

Heart muscle: 560 mcg/Gm

Kidneys: 412 mcg/Gm

Liver: 280 mcg/GmBlood: Small amounts in blood 7-14 meg/ml.Excretion in 24 hrs urine: 50 to 100 meg/ml.Biosynthesis of Carnitine: It is synthesized from lysine and methionine in liver principally, also inkidneys. Synthesis of carnitine is shown below in the box.

Biosynthesis of CarnitineHistorical background:Fraenk^l's vitamin BT is same as carnitine. It

was found to be required as a nutritional factor in meal-worm (Tenebrio molitor). If the meal

worms are fed on a synthetic diet, deficient in vitamin BT they die in 4 to 5 weeks.

Distribution: Carnitine is widely distributed in yeast, milk, liver and particularly large quantitiesin muscles and in meat extracts.

Concentration: Fraenkel used bio-assay technique based on the rate of growth of larvae ofTenebrio molitor and found that in mammals, carnitine content of:

Skeletal muscle: 1 mg/Gm dry weight

Heart muscle: 560 mcg/Gm Kidneys: 412 mcg/Gm

Liver: 280 mcg/Gm

Blood: Small amounts in blood 7-14 meg/ml.Excretion in 24 hrs urine: 50 to 100 meg/ml.

Biosynthesis of Carnitine: It is synthesized from lysine and methionine in liver principally, also in

kidneys. Synthesis of carnitine is shown below in the box.Biosynthesis of CarnitineSuccinate

Functions: Carnitine is considered as a "carrier molecule"; it acts like a ferry-boat. It transports

long-chain acyl-CoA across mitochondrial membrane which is impermeable to acyl-CoA.

Facilitates transport of long-chain acyl-CoA for oxidation in mitochondria.

Facilitates exit of acetyl-CoA and acetoacetyl CoA from within mitochondria to cytosol, where

FA synthesis takes place

Methionine-sparing action: Khairallah and Wolf(1965) found that in rats, carnitine has amethionine-sparing action and may thus be considered a food factor required in marginal diets.

Mechanism of Transport of Long-Chain Acyl-CoA: Activation of lower FA and their oxidation

may occur within the mitochondria, independantly, of carnitine; but long-

plasma lipids 1- in mammals, principal lipids that have metabolic

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