lipid metabolism

LIPID METABOLISMLIPID METABOLISM

DIGETION OF FATSDIGETION OF FATS

FAT DIGESTIONFAT DIGESTION


Fats are a group of substances Fats are a group of substances which form an important part of our which form an important part of our bodies and our diet.bodies and our diet.

They form our cell membranes , They form our cell membranes , prevent loss of heat , act as prevent loss of heat , act as vitamins , store energy, act as vitamins , store energy, act as hormones.hormones.

They provide 9 kcal/mole of energy. They provide 9 kcal/mole of energy. they are stored when their intake is they are stored when their intake is more than we can use in our more than we can use in our physical activities.physical activities.

They cause us to be FAT.They cause us to be FAT.


It starts in the stomach although not It starts in the stomach although not much can be absorbed. Acid stable much can be absorbed. Acid stable lipase or lingual lipase (secreted at the lipase or lingual lipase (secreted at the back of tongue) causes hydrolysis of back of tongue) causes hydrolysis of triacylglycerol Due to acidic pH not triacylglycerol Due to acidic pH not much is digested , only what is acted much is digested , only what is acted upon without emulsification. It is said upon without emulsification. It is said that in infants who have a pH more that in infants who have a pH more towards neutral , it is an important towards neutral , it is an important factor.it digests triacylglycerols with low factor.it digests triacylglycerols with low or medium chain fatty acids also found or medium chain fatty acids also found in milk.in milk.


Bile does the job of emulsifying Bile does the job of emulsifying the lipids and thus greatly the lipids and thus greatly increasing the surface area. increasing the surface area. Peristaltic movements of the Peristaltic movements of the intestine cause a good mixing of intestine cause a good mixing of the contents which helps this the contents which helps this process. process.

The lowering of the pH is also The lowering of the pH is also useful. useful.

Now the pancreatic lipase works Now the pancreatic lipase works on the lipids.on the lipids.


Bile contains bile salts which are cholesterol Bile contains bile salts which are cholesterol derivatives and may form taurocholic acid or derivatives and may form taurocholic acid or glycocholic acid.glycocholic acid.

These increase the surface area.These increase the surface area. As the lipids reach duodenum , they cause As the lipids reach duodenum , they cause

release of a peptide hormone cholecystokinine.release of a peptide hormone cholecystokinine.(CCK).(CCK).

This causes retarded gastric motility. So we very This causes retarded gastric motility. So we very heavy after a high fat meal. This also acts on the heavy after a high fat meal. This also acts on the gall bladder to release bile and on pancreas to gall bladder to release bile and on pancreas to secrete enzymes. Secretin is also released secrete enzymes. Secretin is also released which causes bicarbonate rich secretion from which causes bicarbonate rich secretion from the pancreas to increase the pH of luminal the pancreas to increase the pH of luminal contents.contents.


The pancreatic lipase takes away the The pancreatic lipase takes away the fatty acids at 1,3 positions of a fatty acids at 1,3 positions of a triglyceride leaving monoglyceride and triglyceride leaving monoglyceride and free fatty acids behind. Colipase also free fatty acids behind. Colipase also helps.helps.

Another enzyme, cholesteryl ester Another enzyme, cholesteryl ester hydrolase works on the estersd and hydrolase works on the estersd and gives cholesterol and ffa.gives cholesterol and ffa.

phospholipaseA2 works on phospholipaseA2 works on phospholipases. The lysophospholipid phospholipases. The lysophospholipid (after removal of a fa) is acted upon by a (after removal of a fa) is acted upon by a lysophospholipase. lysophospholipase.


What is now present in the lumen is ffa , What is now present in the lumen is ffa , cholesterol , 2- monoacylglycerol or cholesterol , 2- monoacylglycerol or monoglycerides. These are also monoglycerides. These are also packaged into micelles by the bile packaged into micelles by the bile salts.they are absorbed in the brush salts.they are absorbed in the brush border.inside the mucosal cells , border.inside the mucosal cells , triglycerides are again formed by triglycerides are again formed by acyltransferases. Fa are converted to an acyltransferases. Fa are converted to an activated form by thiokinase or fatty acyl activated form by thiokinase or fatty acyl co A synthetase.co A synthetase.

All long chain fatty acids are used for All long chain fatty acids are used for this purpose.this purpose.

FAT ABSORPTIONFAT ABSORPTION

Medium or small chain fa are directly Medium or small chain fa are directly absorbed in the portal circulation and absorbed in the portal circulation and taken to the liver by albumin. Similarly , taken to the liver by albumin. Similarly , phopholipida are also remade.phopholipida are also remade.

These products are secreted by the These products are secreted by the intestinal cells as chylomicrons into the intestinal cells as chylomicrons into the lacteals or lymph vessels. They are lacteals or lymph vessels. They are carried to the venous system by the carried to the venous system by the thoracic duct. thoracic duct.

These are made up of triacylglycerols These are made up of triacylglycerols and cholesteryl esters. These being very and cholesteryl esters. These being very hydrophobic , are put in the center and hydrophobic , are put in the center and covered up by protein , phospholipid covered up by protein , phospholipid and cholesterol.and cholesterol.

FAT METABOLISMFAT METABOLISM

FAT DIGESTION.FAT DIGESTION.

If this protein , apolipoprotein B- 48 is If this protein , apolipoprotein B- 48 is not made by the mucosa cells, not made by the mucosa cells, triglycerides would accumulate here. triglycerides would accumulate here. This will be congenital This will be congenital abetalipoproteinemia.abetalipoproteinemia.

Now the fate of chylomicrons. These are Now the fate of chylomicrons. These are broken down (triglyceride) in adipose broken down (triglyceride) in adipose and muscle tissiue.and muscle tissiue.

Lipoprotein lipase breaks them down to Lipoprotein lipase breaks them down to fa and glycerol.although rare , its fa and glycerol.although rare , its deficiency causes, type 1 deficiency causes, type 1 hyperlipoprotenemia. This enzyme also hyperlipoprotenemia. This enzyme also travels to other places.travels to other places.


Fa are also taken up by adipose tissue Fa are also taken up by adipose tissue and may be converted to triglycerides and may be converted to triglycerides again. These are the storage form.again. These are the storage form.

Glycerol is used by the liver to form Glycerol is used by the liver to form glycerol 3 phosphate for glucose glycerol 3 phosphate for glucose metabolism. (changed to DHAP).metabolism. (changed to DHAP).

Liver also hydrolyses the remaining part Liver also hydrolyses the remaining part of the chylomicron. If removal of of the chylomicron. If removal of chylomicrons is defective , it causes chylomicrons is defective , it causes them to accumulate there and is known them to accumulate there and is known as type 3 hyperlipoprotenemia. as type 3 hyperlipoprotenemia. Apolipoprotein E is deficient here.Apolipoprotein E is deficient here.


Chylomicrons.Chylomicrons.

chylomicronchylomicron


Fatty acid and triglyceride Fatty acid and triglyceride metabolism along with other lipids metabolism along with other lipids form a part here. We first have a look form a part here. We first have a look at the former substances.at the former substances.

Fa may be free or in esterified form Fa may be free or in esterified form as in triacylglycerols. Levels of ffa as in triacylglycerols. Levels of ffa increase during fasting or starvation increase during fasting or starvation or diabetes.or diabetes.

The structure of fa consists of The structure of fa consists of hydrocarbon chain and a terminal hydrocarbon chain and a terminal carboxyl group. At physiological pH it carboxyl group. At physiological pH it is ionized (coo- , pka 4.8).is ionized (coo- , pka 4.8).


THIS GROUP HAS AFFINITY FOR THIS GROUP HAS AFFINITY FOR WATER.WATER.

Thus fa can remain in water. But longer Thus fa can remain in water. But longer chain fa become more and more chain fa become more and more hydrophobic. so they travel along plasma hydrophobic. so they travel along plasma proteins.Mostly (90%) they travel in proteins.Mostly (90%) they travel in lipoproteins as phospholipids , lipoproteins as phospholipids , triacylglycerol or cholesteryl esters.triacylglycerol or cholesteryl esters.

Double and single bonds. (cis form). Double and single bonds. (cis form). kinking of double bonds and 3 carbon kinking of double bonds and 3 carbon spacing.spacing.

Saturated and unsaturated.Saturated and unsaturated. Sensitivity to oxidation and melting Sensitivity to oxidation and melting

temperature. Tm.temperature. Tm.


Linoleic and linolenic acida are Linoleic and linolenic acida are essential fa.essential fa.

Branched fa in dairy products.Branched fa in dairy products. FATTY ACID SYNTHESIS.FATTY ACID SYNTHESIS.

Fa come in the diet but are also Fa come in the diet but are also synthesized anew in the body from cho synthesized anew in the body from cho or proteins. Acetyl co A is the major fuel. or proteins. Acetyl co A is the major fuel. Liver and mammary glands(when Liver and mammary glands(when lactating) are the major sites. It may also lactating) are the major sites. It may also occur in kidneys or adipose tissue.occur in kidneys or adipose tissue.

First step is the transfer of mitochondrial First step is the transfer of mitochondrial acetyl co A to the cytosol.acetyl co A to the cytosol.


As the co A part cannot traverse the As the co A part cannot traverse the mitochondrial membrane so , the mitochondrial membrane so , the acetate part is transferred only. It is acetate part is transferred only. It is done as citrate formed by condensation done as citrate formed by condensation of oxaloacetate and acetyl co A. of oxaloacetate and acetyl co A.

In the cytosol , citrate is cleaved by In the cytosol , citrate is cleaved by citrate lyase citrate lyase back to a co A and oaa. back to a co A and oaa. However , this transport only occurs However , this transport only occurs when the citrate and ATP when the citrate and ATP concentrations are high as both are concentrations are high as both are needed in fa formation. This also means needed in fa formation. This also means that there is excess of fuels available.that there is excess of fuels available.


Formation of malonyl co A.Formation of malonyl co A. Carboxylation of acetyl co A into malonyl co Carboxylation of acetyl co A into malonyl co

A is carried out by A is carried out by acetyl co A carboxylase. acetyl co A carboxylase. It It has 4 subunits and is activated by citrate. It has 4 subunits and is activated by citrate. It is inhibited by malonyl co A and palmitoyl co is inhibited by malonyl co A and palmitoyl co A (end product). In addition to this , it is also A (end product). In addition to this , it is also phosphorylated and inactivated by phosphorylated and inactivated by epinephrine . When Insulin is present , it is epinephrine . When Insulin is present , it is again activited.again activited.

This enzyme increases in quantity if long This enzyme increases in quantity if long term use of high cho or fa diet is present. term use of high cho or fa diet is present. And in starvation , it decreases.And in starvation , it decreases.


Next , Next , fatty acid synthasefatty acid synthase carries carries rest of the process. It has 7 rest of the process. It has 7 functions and requires a derivative functions and requires a derivative of pantothenic acid , 4 of pantothenic acid , 4 phosphopantetheine. This is used phosphopantetheine. This is used to carry acyl and acetyl units on its to carry acyl and acetyl units on its thiol (-SH) terminal group. Domain thiol (-SH) terminal group. Domain binding with the pan. Acid binding with the pan. Acid derivative is known as the ACP or derivative is known as the ACP or acyl carrier protein. acyl carrier protein.


Molecule of acetate is transferred from Molecule of acetate is transferred from acetyl co A to the ACP.acetyl co A to the ACP.

Then this 2 carbon fragment is Then this 2 carbon fragment is transferred to the enzyme.transferred to the enzyme.

Now the ACP accepts 3 carbon Now the ACP accepts 3 carbon fragment from the malonyl co A. the fragment from the malonyl co A. the enzyme is malonyl co A ACP enzyme is malonyl co A ACP transacylase.transacylase.

Next , the malonyl group looses CO2 Next , the malonyl group looses CO2 and this loss of free energy drives the and this loss of free energy drives the reaction in a forward direction. The reaction in a forward direction. The enzyme is beta ketoacyl ACP synthase.enzyme is beta ketoacyl ACP synthase.


Next the acyl groups are saturated by reduction Next the acyl groups are saturated by reduction and dehydration. Keto groups are converted to and dehydration. Keto groups are converted to alcohol group by the enzyme beta ketoacyl ACP alcohol group by the enzyme beta ketoacyl ACP reductase.reductase.

Next water is removed by beta beta hydroxyacyl Next water is removed by beta beta hydroxyacyl ACP dehydratase.ACP dehydratase.

Enoyl ACP reductase does another reduction.Enoyl ACP reductase does another reduction. The result is a 4 carbon compound with fully The result is a 4 carbon compound with fully

saturated 3 carbons.saturated 3 carbons. This process is repeated 7 times to give a 16 This process is repeated 7 times to give a 16

carbon long fa.carbon long fa. This is a fully saturated molecule of palmitate.This is a fully saturated molecule of palmitate.


All the carbons here belong to malonyl All the carbons here belong to malonyl co A except the first two donated by co A except the first two donated by acetyl co A. acetyl co A.

Major donor of NADPH is HMP. 2 Major donor of NADPH is HMP. 2 molecules of NADPH are made for each molecules of NADPH are made for each molecule of glucose that enters here. molecule of glucose that enters here. NADP dependant malate NADP dependant malate dehydrogenase also produces dehydrogenase also produces significant amounts of NADPH. significant amounts of NADPH.

This process takes place in the cytosol.This process takes place in the cytosol. Glucose metabolism and palmitate Glucose metabolism and palmitate

synthesis have many relations with each synthesis have many relations with each other.other.


Pyruvate which takes part in formation Pyruvate which takes part in formation of mitochondrial acetyl co A.of mitochondrial acetyl co A.

Oaa comes from the gluconeogenesis.Oaa comes from the gluconeogenesis. NADH from glycolysis helps in reduction NADH from glycolysis helps in reduction

of NADP+ to NADPH. of NADP+ to NADPH. Other enzymes in the endoplasmic Other enzymes in the endoplasmic

reticulum and mitochondria can increase reticulum and mitochondria can increase the length of the fa. They can also use the length of the fa. They can also use fa with different chain lengths and fa with different chain lengths and saturation. Beyond 9,10 position saturation. Beyond 9,10 position carbon , humans cannot add double carbon , humans cannot add double bonds thus making linoleic and linolenic bonds thus making linoleic and linolenic acids essential.acids essential.


FATTY ACID OXIDATION.FATTY ACID OXIDATION. Fatty acids are stored in the form of Fatty acids are stored in the form of

triacylglycerol in adipose tissue in an triacylglycerol in adipose tissue in an anhydrous form. Their breakdown gives anhydrous form. Their breakdown gives 9 kcal/mole. Breakdown of fa is known 9 kcal/mole. Breakdown of fa is known as their oxidation.as their oxidation.

First of all the enzyme First of all the enzyme hormone hormone sensitive lipase sensitive lipase hydrolyses the hydrolyses the triglyceride to fa and glycerol. But it triglyceride to fa and glycerol. But it does it at carbon 1 or 3 position only. does it at carbon 1 or 3 position only. The resulting diacylglycerol and then The resulting diacylglycerol and then monoacylglycerol are acted upon by monoacylglycerol are acted upon by other specific lipases.other specific lipases.


Hormone sensitive lipase is activated Hormone sensitive lipase is activated via the cAMP mechanism by many via the cAMP mechanism by many hormones. Insulin or high blood glucose hormones. Insulin or high blood glucose inhibit it. inhibit it.

Fa synthesis and oxidation are Fa synthesis and oxidation are regulated at the same time in opposite regulated at the same time in opposite direction .direction .

Glycerol now released is taken to the Glycerol now released is taken to the liver where liver where glycerol kinaseglycerol kinase enzyme enzyme converts it to glycerol phosphate. This is converts it to glycerol phosphate. This is used in making of triglycerides again or used in making of triglycerides again or also converted to DHAP and be used in also converted to DHAP and be used in glucose metabolism.glucose metabolism.


Fatty acids are bound to albumin Fatty acids are bound to albumin and utilized by tissues for energy and utilized by tissues for energy purposes other than the purposes other than the brain(nervous tissue) , brain(nervous tissue) , RBCs ,adrenal medulla.RBCs ,adrenal medulla.

Beta oxidation is done inside the Beta oxidation is done inside the mitochondria and 2 carbon mitochondria and 2 carbon fragments are removed fragments are removed successively (as they were added) successively (as they were added) from the carboxyl end. Acetyl co A from the carboxyl end. Acetyl co A is produced. is produced.


To get a beta oxidation in the To get a beta oxidation in the mitochondrion , the fa taken up by a cell mitochondrion , the fa taken up by a cell has to be transported inside it. So a co has to be transported inside it. So a co A derivative is formed in the cytoplasm A derivative is formed in the cytoplasm by the enzyme by the enzyme fatty acyl co A fatty acyl co A synthetasesynthetase. It is also called thiokinase.. It is also called thiokinase.

Carnitine is the substance that transfers Carnitine is the substance that transfers this inside the mitochondria.this inside the mitochondria.

An acyl group is transferred first from An acyl group is transferred first from coenzyme A to carnitine by coenzyme A to carnitine by carnitine carnitine acyltransferase 1 acyltransferase 1 forming O forming O acylcarnitine. It is present outside the acylcarnitine. It is present outside the innermembrane.innermembrane.

Fa transFa trans portationportation


Once inside carnitine acyltransferase II Once inside carnitine acyltransferase II transfers this group to a molecule of co transfers this group to a molecule of co enzyme A. enzyme A.

Malonyl co A is the inhibitor of carnitine Malonyl co A is the inhibitor of carnitine acyltransferase 1 . It is a metabolite of fa acyltransferase 1 . It is a metabolite of fa synthesis so it ensures that fa made synthesis so it ensures that fa made outside the mitochondrion are not outside the mitochondrion are not broken down inside it at the same time.broken down inside it at the same time.

Absence or deficiency of enzyme Absence or deficiency of enzyme carnitine acyltransferase or carnitine carnitine acyltransferase or carnitine itself , causes inability to use longer itself , causes inability to use longer chain fa for energy production. This chain fa for energy production. This causes weakness after physical activity. causes weakness after physical activity.

Fa oxid.Fa oxid.


Oxidation of fa consisits of 4 steps Oxidation of fa consisits of 4 steps in which 2 carbon fraction gets in which 2 carbon fraction gets reduced. Each time NADH , reduced. Each time NADH , FADH2 , acetyl co A are formed. FADH2 , acetyl co A are formed. These take place for even These take place for even numbered saturated fa. (n/2)-1.numbered saturated fa. (n/2)-1.

Enzymes needed here include Enzymes needed here include Acyl co A dehydrogenase , enoyl Acyl co A dehydrogenase , enoyl

co A hydratase , beta hydroxyacyl co A hydratase , beta hydroxyacyl co A dehydrogenase , acyl co A co A dehydrogenase , acyl co A acyltransferase.acyltransferase.


Energy yield from this process is 131 ATP IN Energy yield from this process is 131 ATP IN TOTAL minus the 2 ATP used in thiokinase TOTAL minus the 2 ATP used in thiokinase reaction. reaction.

7 NADH molecules are produced. These give 21 7 NADH molecules are produced. These give 21 ATP.ATP.

7 FADH2 molecules are produced. These give 7 FADH2 molecules are produced. These give 14 ATP. 14 ATP.

8 acetyl co A molecules are produced. These 8 acetyl co A molecules are produced. These give 96 ATP.give 96 ATP.

There is a clinical condition where an There is a clinical condition where an acyl co A acyl co A dehydrogenasedehydrogenase for medium chain length fa is for medium chain length fa is deficient. Its occurance is 1 in 10,000. it causes deficient. Its occurance is 1 in 10,000. it causes sever hypoglycaemia. One of important causes sever hypoglycaemia. One of important causes of SIDS.of SIDS.


Odd number carbon fa also undergo Odd number carbon fa also undergo these same reactions and at the end 3 c these same reactions and at the end 3 c propionyl co A remains.this is converted propionyl co A remains.this is converted to methylmalonyl co A. enzyme is to methylmalonyl co A. enzyme is methylmalonyl co A carboxylase. methylmalonyl co A carboxylase.

Next succinyl co A is formed which Next succinyl co A is formed which enters TCA cycle. Enzyme is enters TCA cycle. Enzyme is methylmalonyl co A mutase. It is a methylmalonyl co A mutase. It is a rearrangement of atoms.it requires B12 . rearrangement of atoms.it requires B12 . Deficiency of the enzyme or non Deficiency of the enzyme or non availability of the coenzyme cause availability of the coenzyme cause methylmalonic aciduria. It is inherited methylmalonic aciduria. It is inherited and causes acidosis and retarted and causes acidosis and retarted development.development.

PHOSPHOLIPIDSPHOSPHOLIPIDS

Phospholipids are polar Phospholipids are polar compounds which consist of an compounds which consist of an alcohol group attached to a alcohol group attached to a diacylglycerol or sphingosine diacylglycerol or sphingosine through a phosphodiester through a phosphodiester bridge. They have a hydrophilic bridge. They have a hydrophilic head (phosphate and attached head (phosphate and attached group) , and a hydrophobic tail group) , and a hydrophobic tail (fatty acids).(fatty acids).


The hydrophilic end of a The hydrophilic end of a phospholipid , in a cell phospholipid , in a cell membrane, extends outside it in membrane, extends outside it in the extracellular compartment.the extracellular compartment.

The tail portion also gives The tail portion also gives attachment to other hydrophobic attachment to other hydrophobic groups such as cholesterol , groups such as cholesterol , proteins or glycoproteins.proteins or glycoproteins.

PHOSPHOLIPIDPHOSPHOLIPID

Other phospholipids also play a Other phospholipids also play a role in the body as part of role in the body as part of surfactant secretion in the lung surfactant secretion in the lung and part of a lipoprotein.and part of a lipoprotein.

Classification wise , there are Classification wise , there are two types of phospholipids.two types of phospholipids. Glycerophospholipids.Glycerophospholipids. Sphingophospholipids.Sphingophospholipids.


Glycerophospholipids contain glycerol Glycerophospholipids contain glycerol and are the major class. All of these and are the major class. All of these contain phosphatidic acid which also contain phosphatidic acid which also acts as the group upon which this acts as the group upon which this molecule adds others. molecule adds others.

Phosphatidic acid is a simple structure Phosphatidic acid is a simple structure with a phosphate group on C3 of a with a phosphate group on C3 of a diacylglycerol. The phosphate group diacylglycerol. The phosphate group maybe esterified to an alcohol group , maybe esterified to an alcohol group , for example , of another compound for example , of another compound making new ones.making new ones.


Phosphatidyl serine…PA+serine.Phosphatidyl serine…PA+serine. Similarly we have Similarly we have

Phophatidylcholine.Phophatidylcholine. Phosphatidylethanolamine.Phosphatidylethanolamine. Phosphatidylinositol.Phosphatidylinositol.

Two molecules of PA and glycerol make Two molecules of PA and glycerol make a a cardiolipincardiolipin. It is antigenic.. It is antigenic.

SYNTHESIS.SYNTHESIS. They are synthesized in the endoplasmic They are synthesized in the endoplasmic

reticulum . Diacylglycerol is activated with reticulum . Diacylglycerol is activated with the help of CTP.the help of CTP.


They are then packaged in the golgi They are then packaged in the golgi apparatus and sent to organelle or cell apparatus and sent to organelle or cell membrane or exported outside via membrane or exported outside via exocytosis.exocytosis.

Synthesis of phosphatidylcholine and Synthesis of phosphatidylcholine and phosphatidyl serine can be phosphatidyl serine can be accomplished by already available accomplished by already available choline or ethanolamine. choline or ethanolamine.

These substances are phosphorylated These substances are phosphorylated and activated with CDP .then they are and activated with CDP .then they are transferred to a molecule of transferred to a molecule of diacylglycerol to complete the process.diacylglycerol to complete the process.


Choline is reutilized as it requires Choline is reutilized as it requires methionine (essential amino acid) for methionine (essential amino acid) for the 3 methyl groups, which is deficient in the 3 methyl groups, which is deficient in human diet .human diet .

Again it has an important role in the Again it has an important role in the surfactant secretion in the lungs. surfactant secretion in the lungs. dipalmitoylphosphatidylcholine is dipalmitoylphosphatidylcholine is synthesized in type II pneumocytes synthesized in type II pneumocytes (macrophages) in the alveoli. This (macrophages) in the alveoli. This substance keeps the alveoli patent substance keeps the alveoli patent during expiration by decreasing the during expiration by decreasing the surface tention.surface tention.


Respiratory distress syndrome in the Respiratory distress syndrome in the prematurely born infant sis because of prematurely born infant sis because of the deficiency of this compound.the deficiency of this compound.

Phosphatidylserine is synthesized when Phosphatidylserine is synthesized when free serine replaces ethanolamine of free serine replaces ethanolamine of PE.PE.

Phosphatidylinositol is synthesized from Phosphatidylinositol is synthesized from free inositol and activated CDP free inositol and activated CDP diacylglycerol. It also contains stearic diacylglycerol. It also contains stearic acid and arachidonic acid. It serves as a acid and arachidonic acid. It serves as a reservoir for the latter in the membranes reservoir for the latter in the membranes as arachidonic acid is the precursor of as arachidonic acid is the precursor of PGs. PGs.


PI also has a role in signal PI also has a role in signal transduction. It is membrane transduction. It is membrane bound and phosphorylated in bound and phosphorylated in response to stimulation of cell response to stimulation of cell receptors by many hormones , receptors by many hormones , neurotransmitters or even growth neurotransmitters or even growth factors. Ca mobilization and factors. Ca mobilization and protein kinase activation is used to protein kinase activation is used to produce the desired effects.produce the desired effects.

PI also plays a role in anchoring PI also plays a role in anchoring proteins to the cell membrane. proteins to the cell membrane.


Some proteins present on the Some proteins present on the membranes are attached to PI via a membranes are attached to PI via a carbohydrate. Ex. Are carbohydrate. Ex. Are acetylcholinestrase, lipoprotein lipase acetylcholinestrase, lipoprotein lipase and alkaline phosphatse. This and alkaline phosphatse. This anchorage gives the proteins a lot of anchorage gives the proteins a lot of freedom in movement as they are not freedom in movement as they are not membrane bound but hanging along.membrane bound but hanging along.

Phosphatidylglycerol is a precursor of Phosphatidylglycerol is a precursor of cardiolipin. It is also found in cardiolipin. It is also found in mitochondrial membranes.mitochondrial membranes.


Plasmalogens are phospholipids Plasmalogens are phospholipids that use ether linkage for attaching that use ether linkage for attaching a fa to glycerol. They have an a fa to glycerol. They have an important immunological role. important immunological role. They cause bronchoconstriction They cause bronchoconstriction and vasoconstriction. In short they and vasoconstriction. In short they cause acute inflammation , cause acute inflammation , anaphylactic shock , generate anaphylactic shock , generate oxygen radicals from inflammatory oxygen radicals from inflammatory cells. PAF is also a plasmalogen.cells. PAF is also a plasmalogen.


PHOSPHOLIPID DEGRADATION.PHOSPHOLIPID DEGRADATION. Enzymes involved in this process Enzymes involved in this process

include phospholipase A1 and A2 , include phospholipase A1 and A2 , phospholipase C , and phospholipase D.phospholipase C , and phospholipase D.

Phospholipase C is found in liver while Phospholipase C is found in liver while D variety is found in plants only. A1 and D variety is found in plants only. A1 and A2 are widely distributed in human A2 are widely distributed in human tissues.tissues.

These may also modify the structure of These may also modify the structure of their substrates.their substrates.


They use the fatty acyl co A They use the fatty acyl co A transferase to change fatty acids transferase to change fatty acids on membrane bound lipids.on membrane bound lipids.

SPHINGOMYELINS are degraded SPHINGOMYELINS are degraded by by sphingomyelinasesphingomyelinase. It is present . It is present in the lysosomes. This leaves in the lysosomes. This leaves behind a ceramide after it behind a ceramide after it removes phosphorylcholine. removes phosphorylcholine. Another enzyme , ceramidase , Another enzyme , ceramidase , cleaves this ceraminde. cleaves this ceraminde.


A clinical condition results if A clinical condition results if sphingomyelinase is deficient. It is sphingomyelinase is deficient. It is known as Niemann-Pick disease. It is known as Niemann-Pick disease. It is common in ashkenezi jews. The common in ashkenezi jews. The sphingomyelin keeps on piling up in the sphingomyelin keeps on piling up in the tissue as it is not degraded.liver , spleen tissue as it is not degraded.liver , spleen become greatly enlarged . Infants born become greatly enlarged . Infants born with this disease are mentally severely with this disease are mentally severely retarded as nervous tissue is also retarded as nervous tissue is also affected, so are other parts of the body affected, so are other parts of the body like kidneys , bone marrow. Death is like kidneys , bone marrow. Death is very early.very early.

PROSTAGLANDINSPROSTAGLANDINS

Prostaglandins are a one of a Prostaglandins are a one of a group of substances known as group of substances known as eicosanoids. Others included in eicosanoids. Others included in this group are leukotreines and this group are leukotreines and thromboxanes. These are thromboxanes. These are secreted by blood cells or secreted by blood cells or endothelial cells and are endothelial cells and are concerned with inflammation. concerned with inflammation.

These are potent in even small These are potent in even small quantities and have a wide range quantities and have a wide range of effects.of effects.

PROSTAGLANDINSPROSTAGLANDINS

Although they act as hormones , but Although they act as hormones , but only locally and are produced by almost only locally and are produced by almost all the body tissues, unlike other all the body tissues, unlike other hormones. They are also metabolized hormones. They are also metabolized quickly as there potency may bring quickly as there potency may bring unwanted effects if they are left for long. unwanted effects if they are left for long.

PGs are denoted by letters like A, E , D , PGs are denoted by letters like A, E , D , F , I. F , I.

Linoleic acid is the main precursor which Linoleic acid is the main precursor which is converted into arachidonic is converted into arachidonic acid(20:4(5,8,11,14)). This can also be acid(20:4(5,8,11,14)). This can also be released by phospholipases from released by phospholipases from membrane phospholipids.(PI). membrane phospholipids.(PI).

PG b1PG b1

PG a3PG a3

PG a2PG a2

PGPG

Synthesis of PGs.Synthesis of PGs. In the first step In the first step prostaglandin prostaglandin

endoperoxide synthase complexendoperoxide synthase complex causes causes oxidation and cyclization of arachidonic oxidation and cyclization of arachidonic acid. The products are PGG2 and acid. The products are PGG2 and PGH2.PGH2.

The enzyme is present in microsomes The enzyme is present in microsomes and requires O2 for the and requires O2 for the fatty acid fatty acid cyclooxygenasecyclooxygenase part. The other part part. The other part peroxidaseperoxidase requires reduced glutathione requires reduced glutathione for its activity.for its activity.

PGH2 is a precursor for further PGs and PGH2 is a precursor for further PGs and thromboxanes.thromboxanes.

PGsPGs

The synthase enzyme is inhibited by NSAIDs The synthase enzyme is inhibited by NSAIDs like aspirin. Steroids inhibit phospholipase A2 .like aspirin. Steroids inhibit phospholipase A2 .

Leukotriene synthesis is not affected by Leukotriene synthesis is not affected by NSAIDs. NSAIDs.

Leukotrienes are synthesized via lipooxygenase Leukotrienes are synthesized via lipooxygenase pathway. This enzyme converts arachidonic pathway. This enzyme converts arachidonic acid to 5 hydroxy eicosatetranoic acid (5 acid to 5 hydroxy eicosatetranoic acid (5 HPETE). Different leukotrienes are then HPETE). Different leukotrienes are then synthesized In different tissues. synthesized In different tissues.

These and PGs are involved in affects like pain , These and PGs are involved in affects like pain , vasodilation or constriction, bronchospasm , vasodilation or constriction, bronchospasm , oedema , inflammation in short.oedema , inflammation in short.

PG in DICPG in DIC

KETONE BODIESKETONE BODIES

Liver can produce ketone bodies from Liver can produce ketone bodies from acetyl co A coming from sources such acetyl co A coming from sources such as fa or pyruvate. as fa or pyruvate.

Aceto acetic acid , beta hydroxy butyric Aceto acetic acid , beta hydroxy butyric acid and acetone are the ketone bodies. acid and acetone are the ketone bodies.

These may be converted back to acetyl These may be converted back to acetyl co A in peripheral tissues and used for co A in peripheral tissues and used for energy.(TCA cycle). energy.(TCA cycle).

They are water soluble and even brain They are water soluble and even brain tissue can use them during starvation tissue can use them during starvation times. times.

KETONE BODIESKETONE BODIES

HMG co A is made by HMG co A HMG co A is made by HMG co A synthase in the liver. Further it is synthase in the liver. Further it is cleaved to form ketone bodies.cleaved to form ketone bodies.

Not liver but other tissiues make Not liver but other tissiues make acetyl oc A from ketone bodies acetyl oc A from ketone bodies and thus get energy. They are and thus get energy. They are produced more in starvation and produced more in starvation and uncontrolled diabetes.uncontrolled diabetes.

CHOLESTEROLCHOLESTEROL


A part of cell membrane , it is A part of cell membrane , it is synthesized in all tissues. More so synthesized in all tissues. More so in the liver , intestine , in the liver , intestine , reproductive organs and adrenal reproductive organs and adrenal cortex. It is a sterol and a cortex. It is a sterol and a precursor steroid hormones and precursor steroid hormones and bile acids too. bile acids too.

It comes to the liver from food or It comes to the liver from food or synthesized in the liver or synthesized in the liver or elsewhere in the body. elsewhere in the body.


It leaves the liver as bile salts or in the It leaves the liver as bile salts or in the bile or in the lipoproteins. bile or in the lipoproteins.

Cells require a constant supply of it Cells require a constant supply of it which is regulated by the liver.which is regulated by the liver.

It is the major sterol in humans and It is the major sterol in humans and other animals. other animals.

It is hydrophobic and transported in the It is hydrophobic and transported in the blood only in lipoproteins as itself or as blood only in lipoproteins as itself or as cholesteryl esters.this is a fa at C3 cholesteryl esters.this is a fa at C3 position of cholesterol. position of cholesterol.


Synthesis of cholesterol has to be Synthesis of cholesterol has to be balanced with the intake as it is balanced with the intake as it is very variable in diet of even the very variable in diet of even the same individual. High levels cause same individual. High levels cause coronary artery disease. More coronary artery disease. More secretion in the bile or bile salts secretion in the bile or bile salts causes stone formation in the gall causes stone formation in the gall bladder or the CBD.bladder or the CBD.

First step is the formation of 3-First step is the formation of 3-hydroxy , 3-methylglutaryl Co A.hydroxy , 3-methylglutaryl Co A.(HMG Co A).(HMG Co A).


2 molecules of acetyl Co A molecules 2 molecules of acetyl Co A molecules condense to form acetoacetyl Co A. condense to form acetoacetyl Co A. addition of a third moleculoe forms HMG addition of a third moleculoe forms HMG Co A. enzyme is HMG co A synthase. Co A. enzyme is HMG co A synthase. The synthesis takes place in the cytosol. The synthesis takes place in the cytosol.

Synthesis of mevalonic acid is the next Synthesis of mevalonic acid is the next step. step.

Here the enzyme HMG Co A reductase Here the enzyme HMG Co A reductase releases Co A using 2 molecules of releases Co A using 2 molecules of NADPH for the purpose. This happens NADPH for the purpose. This happens in the endoplasmic reticulum and is the in the endoplasmic reticulum and is the rate limiting step.rate limiting step.

CHOLESTEROL CHOLESTEROL METABOLISMMETABOLISM


Cholesterol itself inhibits the HMG Co A Cholesterol itself inhibits the HMG Co A reductase. So does glucagon. Insulin reductase. So does glucagon. Insulin stimulates (dephosphorylates) the stimulates (dephosphorylates) the enzyme.enzyme.

Mevalonic acid is converted into 5 Mevalonic acid is converted into 5 pyrophosphomevalonate by transfer of 2 pyrophosphomevalonate by transfer of 2 groups of phosphate from ATP.groups of phosphate from ATP.

Next , this substance is decarboxylated Next , this substance is decarboxylated to IPP (isopentanyl pyrophosphate). to IPP (isopentanyl pyrophosphate). Again ATP is required.Again ATP is required.

IPP converts to 3,3 dimethyllyl IPP converts to 3,3 dimethyllyl pyrophosphate (DPP). pyrophosphate (DPP).

IPP and DPP condense to form geranyl IPP and DPP condense to form geranyl pyrophosphate (GPP).pyrophosphate (GPP).


2 molecules of 15 C farsenyl 2 molecules of 15 C farsenyl pyrophosphate combine , are reduced to pyrophosphate combine , are reduced to form 30 C squalene. Enzyme is form 30 C squalene. Enzyme is squalene synthase.squalene synthase.

Squalene is converted to lanosterol by Squalene is converted to lanosterol by squalene monooxygenase requiring O2 squalene monooxygenase requiring O2 and NADPH.and NADPH.

Next cholesterol is formed from Next cholesterol is formed from lanosterol in a multi step process.this lanosterol in a multi step process.this includes removal of methyl bonds and includes removal of methyl bonds and changes in double bonds and changes in double bonds and shortening of the chain to 27 C length. It shortening of the chain to 27 C length. It happens in the ER.happens in the ER.


If the cholesterol is a lot that is If the cholesterol is a lot that is being provided in the being provided in the chylomicrons or LDL then chylomicrons or LDL then transcription of HMG Co A transcription of HMG Co A reductase is decreased. reductase is decreased.

Drugs of the statin group lower Drugs of the statin group lower cholesterol by reversibly , cholesterol by reversibly , competitively inhibiting the HMG competitively inhibiting the HMG Co A reductase.Co A reductase.


It is lost from the body by It is lost from the body by secretion into the bile or bile salts. secretion into the bile or bile salts. It is also altered by the gut It is also altered by the gut bacteria to coprostanol and bacteria to coprostanol and cholestanol.cholestanol.

BILE ACIDS/SALTSBILE ACIDS/SALTS

Bile consists of organic and Bile consists of organic and inorganic substances out of which inorganic substances out of which the important organic substances the important organic substances are PC (lecithin) and bile salts. are PC (lecithin) and bile salts. Important bile salts include cholic Important bile salts include cholic acid and chenodeoxycholic acid.acid and chenodeoxycholic acid.

These are 24 C chain acids with a These are 24 C chain acids with a carboxyl termination and 2,3 carboxyl termination and 2,3 hydroxyl groups. Thus they are hydroxyl groups. Thus they are amphipathic in nature and act as amphipathic in nature and act as emulsifying agents.emulsifying agents.


Before leaving the liver , the bile acids Before leaving the liver , the bile acids are conjugated to glycine, or taurine via are conjugated to glycine, or taurine via amide bond. These are bile salts now amide bond. These are bile salts now and consist of glycocholic acid and and consist of glycocholic acid and glycochenodeoxycholic acid .glycochenodeoxycholic acid .

Taurocholic acid and Taurocholic acid and taurochenodeoxycholic acid.taurochenodeoxycholic acid.

The aa addition causes a carboxyl The aa addition causes a carboxyl group to be fully ionized (-ve) at group to be fully ionized (-ve) at physiological pH.physiological pH.

These are more amphipathic than the These are more amphipathic than the bile acids and thus better at bile acids and thus better at emulsification.emulsification.


Bile salts are reabsorbed actively in the Bile salts are reabsorbed actively in the ileum. This is known as the ileum. This is known as the enterohepatic circulation. About 15 to 30 enterohepatic circulation. About 15 to 30 grams of bile salts are secreted by liver grams of bile salts are secreted by liver in a day while only 0.5 gm are lost. in a day while only 0.5 gm are lost.

If the amount of these salts in the bile is If the amount of these salts in the bile is not enough to keep the cholesterol in a not enough to keep the cholesterol in a solubilized/emulsified form , gall stones solubilized/emulsified form , gall stones result as cholesterol precipitates. This is result as cholesterol precipitates. This is known as cholelithiasis.known as cholelithiasis.

Chenodiol (salt) is used to dissolve Chenodiol (salt) is used to dissolve these stones over a long period of timethese stones over a long period of time

( months to years).( months to years).

LIPOPROTEINSLIPOPROTEINS

LIPOPROTEINS are complexes or LIPOPROTEINS are complexes or combination of proteins and lipids. combination of proteins and lipids. Proteins here, are known as Proteins here, are known as

apolipoproteins and lipids include apolipoproteins and lipids include chlesterol (esterified or non esterified) , chlesterol (esterified or non esterified) , triacylglycerols.triacylglycerols.

These include chylomicrons (CM), low These include chylomicrons (CM), low density lipoproteins (LDL) , very low density lipoproteins (LDL) , very low density lipoproteins (VLDL) and high density lipoproteins (VLDL) and high density lipoproteinn (HDL). density lipoproteinn (HDL).


There is another kind of LDL There is another kind of LDL which is known as SDLDL. which is known as SDLDL.

These things are dynamic These things are dynamic particles. They are synthesized , particles. They are synthesized , catabolised and removed from the catabolised and removed from the circulation.circulation.

Function wise these particles keep Function wise these particles keep the fats soluble in the blood and the fats soluble in the blood and also deliver them to all the tissues.also deliver them to all the tissues.


It is said that the lipoprotein It is said that the lipoprotein delivery of cholesterol is not as delivery of cholesterol is not as efficient in humans as in other efficient in humans as in other animals. This results in deposition animals. This results in deposition of cholesterol in tissues with time , of cholesterol in tissues with time , which may become dangerous which may become dangerous when it starts to block blood when it starts to block blood vessels.vessels.


These are COMPOSED of lipid These are COMPOSED of lipid hydrophobic core containing hydrophobic core containing triglycerideds/cholesteryl esters . triglycerideds/cholesteryl esters . The core is surrounded by a shell The core is surrounded by a shell or outer covering of apoproteins , or outer covering of apoproteins , phospholipids and cholesterol with phospholipids and cholesterol with polar surfaces outwards.polar surfaces outwards.

The LP (lipoproteins) keep on The LP (lipoproteins) keep on changing their protein or lipid changing their protein or lipid content with each other.content with each other.


CM are the largest in size and CM are the largest in size and lowest in density. As they have lowest in density. As they have mostly lipid content and only small mostly lipid content and only small amount of protein. This decreases amount of protein. This decreases in VLDL ,IDL , LDL .HDL has the in VLDL ,IDL , LDL .HDL has the highest amount of proteins.highest amount of proteins.

The proteins serve as structural The proteins serve as structural components as well as receptor components as well as receptor sites. They also act as co sites. They also act as co enzymes during metabolism.enzymes during metabolism.


These are classified from A to H.These are classified from A to H. Metabolism of CHYLOMICRONS.Metabolism of CHYLOMICRONS.

Formed in the mucosa of small Formed in the mucosa of small intestine , they carry fats to all parts of intestine , they carry fats to all parts of the body away from the GIT.the body away from the GIT.

CM are formed in the endoplasmic CM are formed in the endoplasmic reticulum. The enzymes of all the lipids reticulum. The enzymes of all the lipids are also located in the smooth ER. They are also located in the smooth ER. They are then , packed into secretory vesicles are then , packed into secretory vesicles by the golgi apparatus and exported out.by the golgi apparatus and exported out.


This CM contains the B-48 LP. It This CM contains the B-48 LP. It is known as nascent and is further is known as nascent and is further modified in the plasma. Here it modified in the plasma. Here it receives LP E which , in receives LP E which , in conjunction with B-48 , makes this conjunction with B-48 , makes this visible to the liver. visible to the liver.

They also get LP CII which They also get LP CII which activate activate lipoprotein lipaselipoprotein lipase . This . This degrades triacylglycerols in the degrades triacylglycerols in the CM. CM.


The HDL is the source which The HDL is the source which provides these LP. provides these LP.

The enzyme lipoprotein lipase is The enzyme lipoprotein lipase is an extracellular enzyme found in an extracellular enzyme found in the capillaries of most tissues. the capillaries of most tissues. More so in adipose and cardiac More so in adipose and cardiac and skeletal muscle. Deficiency of and skeletal muscle. Deficiency of this enzyme causes type I this enzyme causes type I hyperlipidaemia.hyperlipidaemia.


The CM shanges its form to other The CM shanges its form to other types as it circulates and after types as it circulates and after metabolism , it becomes a metabolism , it becomes a remnant which is taken up by the remnant which is taken up by the liver. It also looses C II LP.liver. It also looses C II LP.

Lysosomes in the liver digest the Lysosomes in the liver digest the left over fats and proteins. The left over fats and proteins. The cholesterol , thus formed , inhibits cholesterol , thus formed , inhibits the enzyme HMG Co A reductase the enzyme HMG Co A reductase reducing cholesterol synthesis.reducing cholesterol synthesis.


The VLDL are carriers of triglycerides. The VLDL are carriers of triglycerides. They are made in the liver. If the level of They are made in the liver. If the level of lipoprotein lipase is less, it will cause lipoprotein lipase is less, it will cause fatty liver . fatty liver . The fats are not removed The fats are not removed quickly enough. It happens in liver quickly enough. It happens in liver disease , alcohol intake or diabetes.disease , alcohol intake or diabetes.

They contain LP B100 and A I. once They contain LP B100 and A I. once again the HDL particles provide them again the HDL particles provide them with C II and E proteins. with C II and E proteins.


The proteins are given back as the The proteins are given back as the VLDL decreases in size . It also VLDL decreases in size . It also exchanges phospholipids and exchanges phospholipids and triacylglycerol for cholesteryl triacylglycerol for cholesteryl esters with the HDL. In the whole esters with the HDL. In the whole process, VLDL is converted to IDL process, VLDL is converted to IDL and then LDL.and then LDL.

LDL have more cholesterol and LDL have more cholesterol and cholesteryl esters and much less cholesteryl esters and much less of triglycerides. of triglycerides.


They have B 100 protein. These are They have B 100 protein. These are utilized by all tissues for cholesterol utilized by all tissues for cholesterol uptake.uptake.

Type II hyperlipidemia occurs when LDL Type II hyperlipidemia occurs when LDL receptors are deficient in numbers. It receptors are deficient in numbers. It raises blood cholesterol but not raises blood cholesterol but not triglycerides.triglycerides.

LDL is broken down into simpler LDL is broken down into simpler components in the cells by enzymes in components in the cells by enzymes in endosomes. The amount of cholesterol endosomes. The amount of cholesterol regulates the number of cell receptors regulates the number of cell receptors up or down and more of it also inhibits up or down and more of it also inhibits cholesterol synthesis.cholesterol synthesis.


Excess cholesterol is stored as Excess cholesterol is stored as cholesteryl ester by adding fatty cholesteryl ester by adding fatty acids to it through acids to it through acyl co A: acyl co A: cholesterol acyl transferase.cholesterol acyl transferase.

These LDL particles are important These LDL particles are important in forming the atherosclerotic in forming the atherosclerotic plaques in the blood vessels , plaques in the blood vessels , especially coronary arteries. They especially coronary arteries. They can get oxidized at the can get oxidized at the polyunsaturated fatty acid level.polyunsaturated fatty acid level.


Antioxidants like vit. E helps Antioxidants like vit. E helps prevent this phenomenon. This prevent this phenomenon. This causes changes in the B causes changes in the B protein.This changed particle is protein.This changed particle is taken up by the macrophages taken up by the macrophages which are scavenging and have which are scavenging and have broad spectrum receptors for the broad spectrum receptors for the purpose.purpose.

The problem with this LDL is that it The problem with this LDL is that it does not inhibit cholesterol does not inhibit cholesterol sythesis ! Loss of regulation!sythesis ! Loss of regulation!


This causes constant intake by the This causes constant intake by the macrophages and they turn into foam macrophages and they turn into foam cells! Laden with cholesterol.cells! Laden with cholesterol.

HDL are also synthesized by the liver . HDL are also synthesized by the liver . They do the important job of giving other They do the important job of giving other particles (chylomicrons and VLDL) the particles (chylomicrons and VLDL) the apo CII. This causes triglyceride apo CII. This causes triglyceride digestion . It also causes free digestion . It also causes free cholesterol in the extrahepatic tissues cholesterol in the extrahepatic tissues be esterified by PCAT and LCAT.be esterified by PCAT and LCAT.

These are phosphatidylcholine (P) or These are phosphatidylcholine (P) or Lecithin(L):cholesterol acyl transferase . Lecithin(L):cholesterol acyl transferase .


It also recovers these proteins from It also recovers these proteins from other particles before they are taken up other particles before they are taken up by cells.by cells.

Itself HDL contains cholesterol and Itself HDL contains cholesterol and phosphatidylcholine in addition to apo phosphatidylcholine in addition to apo A , C and E. it has the capability to A , C and E. it has the capability to absorb free cholesterol. This is esterified absorb free cholesterol. This is esterified by PCAT which is stimulated by apo A I by PCAT which is stimulated by apo A I of HDL. This is then exchanged with of HDL. This is then exchanged with VLDL . It is ultimately metabolized inside VLDL . It is ultimately metabolized inside cells.cells.

LIPOPROTEIN METABOLISMLIPOPROTEIN METABOLISM


HDL is taken up by the liver and HDL is taken up by the liver and cholesterol released is again cholesterol released is again packed into lipoproteins or in the packed into lipoproteins or in the bile or bile acids.bile or bile acids.

STEROID HORMONESSTEROID HORMONES

Cholesterol is the precursor of Cholesterol is the precursor of all steroid hormones.all steroid hormones.

These includeThese include Mineralocorticoids secreted by the Mineralocorticoids secreted by the

adrenal cortex . Ex. aldosterone.adrenal cortex . Ex. aldosterone. Glucocorticoids secreted by the Glucocorticoids secreted by the

adrenal cortex. Ex. Cortisol.adrenal cortex. Ex. Cortisol. Sex hormones secreted by Sex hormones secreted by

ovaries and testes. Ex. Estrogens ovaries and testes. Ex. Estrogens and androgens etc.and androgens etc.

STEROIDSSTEROIDS

These hormones act elsewhere in These hormones act elsewhere in the body and being non-polar they the body and being non-polar they are carried by specific plasma are carried by specific plasma proteins. (sex hor. Binding pt. , proteins. (sex hor. Binding pt. , transcortin for cortisol).transcortin for cortisol).

Albumin works as a general Albumin works as a general carrier for all of these. carrier for all of these.

SYNTHESIS.SYNTHESIS. In general , all are synthesized by In general , all are synthesized by

the same precursor , cholesterol. the same precursor , cholesterol.

STEROIDSSTEROIDS

They are made almost as a continuous They are made almost as a continuous process. One hormone made after the process. One hormone made after the other in an orderly fashion. other in an orderly fashion.

Considering this situation, we can also Considering this situation, we can also bring in mind that if an enzyme , bring in mind that if an enzyme , somewhere , is deficient or missing it somewhere , is deficient or missing it will adversely affect the production of will adversely affect the production of hormones downstream or may bring the hormones downstream or may bring the process to a complete halt. process to a complete halt.

A series of diseases occurs which shall A series of diseases occurs which shall be discussed later. be discussed later.

STEROIDSSTEROIDS

During the early phases of During the early phases of synthesis , the hydrocarbon synthesis , the hydrocarbon chain of cholesterol is shortened chain of cholesterol is shortened and its steroid nucleus is and its steroid nucleus is hydroxylated.hydroxylated.

The first step is rate limiting and The first step is rate limiting and needs O2 and NADPH. The needs O2 and NADPH. The enzyme is enzyme is desmolase complexdesmolase complex. . The product is pregnenolone.The product is pregnenolone.

STEROIDSSTEROIDS

Pregnenolone is oxidised and Pregnenolone is oxidised and isomerised to isomerised to progesteroneprogesterone . . Here onwards , all the hormones Here onwards , all the hormones whether sex or glucocorticoids or whether sex or glucocorticoids or mineralocorticoids are formed. mineralocorticoids are formed. This occurs by further This occurs by further hydroxylation of progesterone and hydroxylation of progesterone and the subsequent products at all the subsequent products at all levels. levels.

STEROIDSSTEROIDS

Deficiency of an enzyme at one Deficiency of an enzyme at one level causes the product to level causes the product to become deficient and the previous become deficient and the previous substrate to accumulate due to the substrate to accumulate due to the feedback process. feedback process.

This causes some serious This causes some serious metabolic and hormonal affects on metabolic and hormonal affects on the body.the body.

STEROIDSSTEROIDS

The secretion of hormones is controlled The secretion of hormones is controlled by the hypothalamus and the pituitary by the hypothalamus and the pituitary gland. gland.

The hypothalamus releases The hypothalamus releases corticotropin releasing factorcorticotropin releasing factor which which causes release of ACTH causes release of ACTH (adrenocorticotropic hormone). This (adrenocorticotropic hormone). This causes release of glucocorticoids. causes release of glucocorticoids.

These are secreted in stress. They These are secreted in stress. They cause protein breakdown and cause protein breakdown and gluconeogenesis.gluconeogenesis.

STEROIDSSTEROIDS

Aldosterone is secreted by the Aldosterone is secreted by the ratio of Na+/K+ . It is also ratio of Na+/K+ . It is also stimulated by angiotensin. It stimulated by angiotensin. It controls the Na+ in the body. It controls the Na+ in the body. It causes absorption of sodium and causes absorption of sodium and secretion of K+ from the kidneys.secretion of K+ from the kidneys.

From the hypothalamus , From the hypothalamus , gonadotropin releasing gonadotropin releasing hormonehormone , causes secretion of , causes secretion of two hormones from the anterior two hormones from the anterior pituitary.pituitary.

STEROIDSSTEROIDS

One hormone , FSH (follicle One hormone , FSH (follicle stimulating hormone),causes the stimulating hormone),causes the testes to produce sperms and the testes to produce sperms and the ovaries to produce follicles.ovaries to produce follicles.

The other one LH (luteinizing The other one LH (luteinizing hormone) increases the effect of hormone) increases the effect of FSH and itself causes the release FSH and itself causes the release of androgens from the testes and of androgens from the testes and estrogens from the ovaries.estrogens from the ovaries.

STEROIDSSTEROIDS

STEROIDSSTEROIDS

All the steroid hormones affect by All the steroid hormones affect by combining with specific cell surface combining with specific cell surface receptors and internalizing into the cells receptors and internalizing into the cells and reaching the nucleus. and reaching the nucleus.

Here they cause transcription and then Here they cause transcription and then translation to cause changes in protein translation to cause changes in protein (such as enzymes)(such as enzymes)

production and thus produce affects.production and thus produce affects.

Their affect holds on longer and comes Their affect holds on longer and comes later due to this method.later due to this method.

STEROIDSSTEROIDS

SATEROIDSSATEROIDS

STEROIDSSTEROIDS

For catabolism steroids are For catabolism steroids are metabolised in the liver and there metabolised in the liver and there hydroxylated. Further more , there hydroxylated. Further more , there unsaturated bonds are reduced. unsaturated bonds are reduced. They are conjugated with They are conjugated with glucoronic acid or sulphate to be glucoronic acid or sulphate to be excreted by the kidneys. This excreted by the kidneys. This conjugation makes them more conjugation makes them more water soluble. 20 %- 30 % are water soluble. 20 %- 30 % are secreted in bile. Rest by the secreted in bile. Rest by the kidney.kidney.

lipid metabolism

Documents

free fatty acids

medium chain fatty acids

long chain fatty acids

fatty acyl

acid stable lipase

lingual lipase

ph of luminal

bile salts