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Different types of Fatty Oxidation

Different types of fatty acid oxidation

Q. 1

Oxidation of odd-chain fatty acids result in the production of which of the following?

 A

Acetyl CoA

 B

Succinyl CoA

 C

Propionyl CoA

 D

Malonyl CoA

Q. 1

Oxidation of odd-chain fatty acids result in the production of which of the following?

 A

Acetyl CoA

 B

Succinyl CoA

 C

Propionyl CoA

 D

Malonyl CoA

Ans. C

Explanation:

Odd chain fatty acids are also oxidised exactly as even chain fatty acids. However, after successive removal of 2-carbon units, at the end, one 3 carbon unit, propionyl CoA is produced. The propionyl CoA is further metabolised to Succinyl CoA which enters the TCA cycle.
 
Ref: Vasudevan Biochemistry, 3rd Edition, Page 124

 


Q. 2

Fatty acid with even number of carbon atoms on oxidation produces:

 A

Acetyl CoA

 B

Succinyl CoA

 C

Propionyl CoA

 D

All of the above

Q. 2

Fatty acid with even number of carbon atoms on oxidation produces:

 A

Acetyl CoA

 B

Succinyl CoA

 C

Propionyl CoA

 D

All of the above

Ans. A

Explanation:

Fatty acids with an odd number of carbon atoms are oxidized by the pathway of β-oxidation, producing acetyl-CoA, until a three-carbon (propionyl-CoA) residue remains. This compound is converted to succinyl-CoA, a constituent of the citric acid cycle. Hence, the propionyl residue from an odd-chain fatty acid is the only part of a fatty acid that is glucogenic
         
Ref: Harper 28th edition, chapter 22.

Q. 3

Very long chain fatty acid is oxidised in:

 A

Mitochondria

 B

Cytoplasm

 C

Peroxisome

 D

All of the above

Q. 3

Very long chain fatty acid is oxidised in:

 A

Mitochondria

 B

Cytoplasm

 C

Peroxisome

 D

All of the above

Ans. C

Explanation:

A modified form of oxidation is found in peroxisomes and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by catalase.
Thus, this dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP. The system facilitates the oxidation of very long chain fatty acids (eg, C20, C22).
These enzymes are induced by high-fat diets and in some species by hypo-lipidemic drugs such as clofibrate.
Ref: Harper 28th edition, chapter 22.

Q. 4

Beta-oxidation of odd-chain fatty acids produces:

 A

Acetyl CoA

 B

Malonyl CoA

 C

Succinyl CoA

 D

Propionyl CoA

Q. 4

Beta-oxidation of odd-chain fatty acids produces:

 A

Acetyl CoA

 B

Malonyl CoA

 C

Succinyl CoA

 D

Propionyl CoA

Ans. D

Explanation:

Odd chain fatty acids are oxidized in the similar manner as of even chain fatty acid, beta-oxidation.

However, unlike even chain fatty acids which yields only acetyl CoA, odd chain fatty acids will yield Acetyl-CoA and one three carbon acid, Propionyl-CoA.

Propionyl CoA is further converted into succinyl CoA.                                                                                                                                                      
Fatty acids are an important source of energy. ?Oxidation is the process where energy is produced by degradation of fatty acids.

 

Beta Oxidation of fatty acids: The pathway for catabolism of fatty acids is referred to  as the b-oxidation pathway, because oxidation occurs at the b-carbon (C-3).
?The beta oxidation of fatty acids involve three stages:
1. Activation of fatty acids in the cytosol
2. Transport of activated fatty acids into mitochondria (carnitine shuttle)
3. Beta oxidation proper in the mitochondrial matrix.
 
1. Activation of Fatty Acid:
 
This proceeds by Fatty Acid  thiokinase (acyl COA synthetase) present in cytosol. Thiokinase requires ATP, COA SH, Mg++. The product of this reaction is Fatty Acid  acyl COA and water.
2. Transport of fatty acyl CoA from cytosol into mitochondria: (rate-limiting step) ?Long chain acyl CoA traverses the inner mitochondria membrane with a special transport mechanism called Carnitine shuttle.
  • Acyl groups from acyl COA is transferred to carnitine to form acyl carnitine catalyzed by carnitine acyltransferase I, in the outer mitochondrial membrane.
  • Acylcarnitine is then shuttled across the inner mitochondrial membrane by a translocase enzyme.
  • The acyl group is transferred back to CoA in matrix by carnitine acyl transferase II.
  • Finally, carnitine is returned to the cytosolic side by translocase, in exchange for an incoming acyl carnitine.
3. Proper of β – oxidation in the mitochondrial matrix:
There are 4 steps in β – oxidation
  • Step I – Oxidation by FAD linked dehydrogenase: oxidation of acyl CoA by an acyl CoA dehydrogenase to give α-β unsaturated acyl CoA (enoyl CoA). 
  • Step II – Hydration by Hydratase: hydration of the double bond to β-hydroxyacyl CoA (p-hydroxyacyl CoA).
  • Step III – Oxidation by NAD linked dehydrogenase: oxidation of β-hydroxyacyl CoA to produce β-Ketoacyl CoA a NAD-dependent reaction.
  • Step IV – Thiolytic clevage Thiolase:? cleavage of the two carbon fragment by splitting the bond between α and β carbons, by thiolase enzyme.
Beta oxidation of odd chain fatty acids:
Fatty acids that enter beta-oxidation with an even number of carbons are converted entirely to acetyl-CoA. The beta-oxidation of odd chain fatty acid results in a acetyl-CoA and the 3-carbon chain propionyl-CoA. Propionyl Coa is further converted to succinyl CoA.
Ref: Harper’s, Illustrated Biochemistry, 26th edition, Page 182

Quiz In Between


Q. 5

β-oxidation of odd-chain fatty acids produces:

 A

Succinyl CoA

 B

Propionyl CoA

 C

Acetyl CoA

 D

Malonyl CoA

Q. 5

β-oxidation of odd-chain fatty acids produces:

 A

Succinyl CoA

 B

Propionyl CoA

 C

Acetyl CoA

 D

Malonyl CoA

Ans. B

Explanation:

B i.e. Propionyl CoA

13- oxidation of odd chain fatty acid produces acetyl CoA plus a molecule of propionyl –CoAQ. But propionyl CoA is formed only in odd chain fatty acid oxidation (not in even fatty acids)


Q. 6

Short chain fatty acid produced by bacteria are maximally absorbed in :

 A

Duodenum

 B

Colon

 C

Ileum

 D

Jejunum

Q. 6

Short chain fatty acid produced by bacteria are maximally absorbed in :

 A

Duodenum

 B

Colon

 C

Ileum

 D

Jejunum

Ans. B

Explanation:

B i.e. Colon

  • Major fat absorption takes place in upper small intestine except (mainly jejunum & duodenum) short chain fatty acids which is absorbed in colon0.
  • Normal fecal fat excretion is less than 6gm/day, more than 6gm/day indicates malabsorptionQ.
  • Steatorrhea is defined as stool fat > 7gm/dayQ.
  • Daily fecal fat averages 15-25gm/d with small intestinal disease & exceeds 40gm /d with pancreatic exocrine insufficiency
  • Evaluation of fat malabsorption:

Q. 7

Oxidation of very long chain fatty acids takes place in ‑

 A

Cytosol

 B

Mitochondria

 C

Ribosomes

 D

Peroxisomes

Q. 7

Oxidation of very long chain fatty acids takes place in ‑

 A

Cytosol

 B

Mitochondria

 C

Ribosomes

 D

Peroxisomes

Ans. D

Explanation:

Quiz In Between



Different types of Fatty Oxidation

Different types of Fatty Oxidation


DIFFERENT TYPES OF FATTY ACID OXIDATION

Oxidation of Very Long Chain Fatty Acid-

  • It takes place in Peroxisomes till Octanoyl CoA.
  • Oxidation in peroxisome produces Acetyl CoA and H2O2.

Clinical Corelation-

  1. Peroxisomal Ghost
  2. Zellweger’s syndrome- is a rare inborn error of peroxisomal fatty acid oxidation.
  3. Neonatal adrenoleukodystrophy
  4. Infantile Refsum disease

Oxidation of Unsaturated Fatty Acid-

  • It occurs in mitochondria
  • The energy yield by oxidation of Unsaturated Fatty Acid is 1.5 ATP less per double bond.

Oxidation of Odd Chain Fatty Acid-

  • It takes place in mitochondria
  • Odd chain fatty acids are also Beta-oxidized normally but the last step produces a 3-carbon propionyl.
  • This three carbon units (propionl CoA) from odd chain fatty acids is the only part of a fatty acid that is glucogenic. 

Alpha- oxidation of fatty acids

  • It occurs in endoplasmic reticulum and mitochondria

Exam Important

  • Oxidation of Very Long Chain Fatty Acid- It takes place in Peroxisomes till Octanoyl CoA.
  • Oxidation in peroxisome produces Acetyl CoA and H2O2
  • Oxidation of Unsaturated Fatty Acid- It occurs in mitochondria
  • The energy yield by oxidation of Unsaturated Fatty Acid is 1.5 ATP less per double bond.
  • Odd chain fatty acids are also Beta-oxidized normally but the last step produces a 3-carbon propionyl.
  • Alpha- oxidation of fatty acids–  It occurs in endoplasmic reticulum and mitochondria.
Don’t Forget to Solve all the previous Year Question asked on Different types of Fatty Oxidation

Module Below Start Quiz

Rapoport- Leubering Cycle

Rapoport Leubering cycle

Q. 1

The phenomenon of cancer cells switching to glycolysis even in the presence of adequate oxygen for oxidative phosphorylation is known as:

 A

Tyndall effect

 B

Warburg effect

 C

Hawthorne effect

 D

None of the above

Q. 1

The phenomenon of cancer cells switching to glycolysis even in the presence of adequate oxygen for oxidative phosphorylation is known as:

 A

Tyndall effect

 B

Warburg effect

 C

Hawthorne effect

 D

None of the above

Ans. B

Explanation:

Even in the presence of ample oxygen, cancer cells shift their glucose metabolism away from the oxygen hungry, but efficient, mitochondria to glycolysis.
This phenomenon, called the Warburg effect and also known as aerobic glycolysis, has been recognized for many years (indeed, Otto Warburg received the Nobel Prize for discovery of the effect that bears his name in 1931), but was largely neglected until recently.

This metabolic alteration is so common to tumors that some would call it the eighth hallmark of cancer.
             
Ref:
Robbins 8th edition Chapter 2.

Q. 2

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

 A

Hypoxia stimulates pyruvate dehydrogenase by increased 2,3 DPG

 B

Hypoxia inhibits hexokinase

 C

Hypoxia stimulates release of all glycolytic enzymes from band 3 on RBC membrane

 D

Activation of the regulatory enzymes by high PH

Q. 2

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

 A

Hypoxia stimulates pyruvate dehydrogenase by increased 2,3 DPG

 B

Hypoxia inhibits hexokinase

 C

Hypoxia stimulates release of all glycolytic enzymes from band 3 on RBC membrane

 D

Activation of the regulatory enzymes by high PH

Ans. C

Explanation:

During Hypoxia, the glycolytic enzymes that bind in the same region of band 3 of Hb are released from the membrane resulting in an increased rate of glycolysis. Increased glycolysis increases ATP production and the hypoxic release of ATP.
 
Ref: Oxygen Transport to Tissue, Xxxiii, edited by Martin Wolf, David K Harrison, 2012, Page 188.

Q. 3

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

 A

Hypoxia Stimulates pyruvate dehydrogenase by increased 2,3 DPG

 B

Hypoxia inhibits hexokinase

 C

Hypoxia stimulates release of all Glycolytic enzymes from Band 3 on RBC membrane

 D

Activation of the regulatory enzymes by high PH

Q. 3

Within the RBC, hypoxia stimulates glycolysis by which of the following regulating pathways?

 A

Hypoxia Stimulates pyruvate dehydrogenase by increased 2,3 DPG

 B

Hypoxia inhibits hexokinase

 C

Hypoxia stimulates release of all Glycolytic enzymes from Band 3 on RBC membrane

 D

Activation of the regulatory enzymes by high PH

Ans. C

Explanation:

C i.e. Hypoxia stimulates release of all glycolytic enzymes from Band 3 on RBC membrane

RBC membrane cytoskeletal protein spectrin is anchored to transmembrane anion exchanger protein Band 3 by protein ankyrin & protein 4.2. Another cytoskeletal protein actin is attached to transmembrane glycophorin C by protein 4.1. Tropomyosin, tropomodulin, adducin and 4.9 are other proteins.

  • Band 3, is a multifunction RBC transmembrane protein, which is important for its cytoskeletal structure, cell shape, anion exchange activity and glycolysisQ. Band 3 is responsible for chloride shift in RBCQ. Hypoxic deoxygenation of hemoglobin causes Band 3 tyrosine phosphorylation and thereby stimulates glycolysis by releasing glycolytic enzymes from band 3 on RBC membraneQ.
  • In kidney, I cells contain Band 3, an anion exchange protein in their basolateral cell membrane, which may function as a

Cl- – HCO3 exchanger for the transport of HCO3 to interstitial fluid.

  • In animal cells, principal regulators of intracellular pH are HCO3 transporters such as Band 3 CI – Hog; exchanger, 3Na+ – Hcq cotransporters and a le – HCO3 cotransporter.

Q. 4

Number of ATP produced by RBC when Glycolysis occurs through Rapoport Leubering pathway

 A

1

 B

2

 C

3

 D

4

Q. 4

Number of ATP produced by RBC when Glycolysis occurs through Rapoport Leubering pathway

 A

1

 B

2

 C

3

 D

4

Ans. A

Explanation:

 

Usually 2 ATP molecules are formed in glycolysis by substrate level phosphorylation.

Quiz In Between



Rapoport- Leubering Cycle

Rapoport- Leubering Cycle


  • Rapoport- Leubering Cycle occurs in RBCs (erythrocytes).

  • In this cycle, 1,3 – BPG is converted into 2, 3 –BPG by an enzyme biphosphoglycerate  mutase.
  • 2,3- BPG is then converted into 3- phosphoglycerate by enzyme 2,3- biphosphoglycerate phosphatase. 

Significance of Rapaport- Leubering Cycle-

  • The 2, 3 – BPG combines with haemoglobin and reduces the affinity towards oxygen. So, its presence has oxyhemoglobin unloads more oxygen to the tissues.
  • 2,3BPG shifts the oxygen Dissociation curve to right.
  • If the glycolysis of RBCs is impaired there will be impaired synthesis of 2, 3 – BPG  which causes left shift of O2  dissociation curve and increase oxygen affinity of haemoglobin.
  • Under hypoxic, high altitude, fetal tissues, anaemic condition the 2, 3- BPG concentration in the RBC increases.

Exam Important

  • Rapoport Leubering cycle occurs in erythrocytes
  • 2, 3 –bisphosphoglycerate combines with hemoglobin & reduces affinity towards oxygen.
  • 2,3 BPG shifts the oxygen Dissociation curve to right due to reduced affinity towards oxygen
  • No ATP is generated (only one molecule generated through glycolysis in RBC utilized)
  • Under hypoxic conditions, 2, 3- BPG increases in RBCs
  • Cancer cells switching to glycolysis even in the presence of adequate O2 for oxidative phosphorylation c/d Warburg effect
Don’t Forget to Solve all the previous Year Question asked on Rapoport- Leubering Cycle

Module Below Start Quiz

Metabolism of Chylomicron

Metabolism of Chylomicron

Q. 1 In chylomicrons, the Principle Apo-protein is:
 A Apo A-I
 B Apo A-II
 C Apo B-100
 D Apo B-48
Q. 1 In chylomicrons, the Principle Apo-protein is:
 A Apo A-I
 B Apo A-II
 C Apo B-100
 D Apo B-48
Ans. D

Explanation:

Apo B-48


Q. 2

Which of the following are incorporated into the core of nascent chylomicrons?

 A

Triglyceride

 B

Triglyceride and Cholesterol

 C

Triglyceride, Cholesterol and Phospholipids

 D

Free fatty acids

Q. 2

Which of the following are incorporated into the core of nascent chylomicrons?

 A

Triglyceride

 B

Triglyceride and Cholesterol

 C

Triglyceride, Cholesterol and Phospholipids

 D

Free fatty acids

Ans. B

Explanation:

After ingestion of a meal, dietary fat (triglyceride) and cholesterol are absorbed into the cells of the small intestine and are incorporated into the core of nascent chylomicrons.


Q. 3

The chyle from intestine is rich with chylomicrons. Which of the following form the protein core of chylomicrons?

 A

Triglyceride only

 B

Triglyceride + cholesterol

 C

Triglyceride + cholesterol + phospholipid

 D

Only cholesterol

Q. 3

The chyle from intestine is rich with chylomicrons. Which of the following form the protein core of chylomicrons?

 A

Triglyceride only

 B

Triglyceride + cholesterol

 C

Triglyceride + cholesterol + phospholipid

 D

Only cholesterol

Ans. C

Explanation:

The triacylglycerol, cholesterol ester and phospholipid molecules along with apoproteins B48, and apo-A are incorporated into chylomicrons.
 

Four major groups of lipoproteins:

  • Chylomicrons, derived from intestinal absorption of triacylglycerol and other lipids.
  • Very low density lipoproteins (VLDL, or pre–lipoproteins), derived from the liver for the export of triacylglycerol.
  • Low-density lipoproteins (LDL, or -lipoproteins), representing a final stage in the catabolism of VLDL.
  • High-density lipoproteins (HDL, or -lipoproteins), involved in cholesterol transport and also in VLDL and chylomicron metabolism.

Triacylglycerol is the predominant lipid in chylomicrons and VLDL, whereas cholesterol and phospholipid are the predominant lipids in LDL and HDL, respectively.

Ref: Botham K.M., Mayes P.A. (2011). Chapter 25. Lipid Transport & Storage. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.

Quiz In Between


Q. 4

A human subject takes part in a nutritional research study. After ingesting a very fatty meal, serum samples are taken for research studies at 1 hour and 3 hours. These studies measure the average diameter of the chylomicrons, showing an average chylomicron diameter of 500 nm at 1 hour, which drops to an average diameter of 150 nm at 3 hours. Where is the enzyme responsible for this change located?

 A

Adipocytes

 B

Endothelial cells

 C

Enterocytes

 D

Hepatocytes

Q. 4

A human subject takes part in a nutritional research study. After ingesting a very fatty meal, serum samples are taken for research studies at 1 hour and 3 hours. These studies measure the average diameter of the chylomicrons, showing an average chylomicron diameter of 500 nm at 1 hour, which drops to an average diameter of 150 nm at 3 hours. Where is the enzyme responsible for this change located?

 A

Adipocytes

 B

Endothelial cells

 C

Enterocytes

 D

Hepatocytes

Ans. B

Explanation:

Chylomicrons are produced by enterocytes (intestinal epithelial cells), using gut luminal triglycerides for the source of the lipid. The chylomicrons are secreted into the gut lymphatic system, and from there drain eventually into the systemic venous system from the thoracic duct, and hence into the serum portion of the blood. They are initially large and have a very high triglyceride content. With time, lipoprotein lipase releases triglycerides from the chylomicron core by hydrolyzing them to more easily absorbed fatty acids. The enzyme is located on the external surface of the vascular endothelium of tissues with triglyceride needs such as skeletal muscle, cardiac muscle tissue, and lactating breast. The result of lipoprotein lipase activity is that the chylomicrons shrink in size.

While adipose tissue can utilize chylomicrons, lipoprotein lipase is located on the endothelial cells rather than adipocytes. Adipocytes have an adipose tissue lipase, which is an intracellular enzyme that can cleave triglycerides to glycerol and fatty acids, allowing them to be released into the circulation when chylomicrons are low.
 
Enterocytes have the ability to pick up mixed micelles from the gut lumen for repackaging in the smooth endoplasmic reticulum as chylomicrons.
Hepatocytes pick up the chylomicron remnants after the lipoprotein lipase shrinks them.
Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 26. Digestion, Absorption, & Nutritional Principles. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.

Q. 5

Which helps in the transport of chylomicrons from intestine to liver :

 A

Apoprotein B

 B

Apoprotein A

 C

Apoprotein C

 D

Apoprotein E

Q. 5

Which helps in the transport of chylomicrons from intestine to liver :

 A

Apoprotein B

 B

Apoprotein A

 C

Apoprotein C

 D

Apoprotein E

Ans. A

Explanation:

A i.e. Apoprotein B


Q. 6

Major apolipoprotein of chylomicrons

 A

B-100

 B

D

 C

B-48

 D

None

Q. 6

Major apolipoprotein of chylomicrons

 A

B-100

 B

D

 C

B-48

 D

None

Ans. C

Explanation:

Ans. is ‘c’ i.e., B-48 

Quiz In Between



Metabolism of Chylomicron

Metabolism of Chylomicron


LIPOPROTEIN METABOLISM

Chylomicron Metabolism

  • Chylomicrons transport the dietry lipid from intestine to liver.
  • Function of chylomicrons is to transport exogenous triglyceride to adipose tissue (for storage).
  1. Step I- Formation of Nascent Chylomicron- contains triglyceride, cholestryl ester, cholesterol, lipid, apo B-48 & apo A.
  2. Step II- Formation of Mature Chylomicron- by receiving apo C-II and apo E from HDL.
  3. Step III- Formation of Remanant Chylomicron– Apo C-II activates Lipoprotein Lipase
  4. Step IV- Uptake of Remnant Chylomicron
  • Chylomicron remnant is taken up by the liver.
  • Uptake is mediated by apo E via two apo E dependent recptors, LDL  receptor and LDL receptor related protein-I (LRP-I).

Exam Important

  • Chylomicrons transport the dietry lipid from intestine to liver.
  • Function of chylomicrons is to transport exogenous triglyceride to adipose tissue (for storage).
  1. Step I- Formation of Nascent Chylomicron
  2. Step II- Formation of Mature Chylomicron- by receiving apo C-II and apo E from HDL.
  3. Step III- Formation of Remanant Chylomicron- Apo C-II activates Lipoprotein Lipase
  4. Step IV- Uptake of Remnant Chylomicron-
  • Chylomicron remnant is taken up by the liver.
  • Uptake is mediated by apo E via two apo E dependent recptors, LDL  receptor and LDL receptor related protein-I (LRP-I).
Don’t Forget to Solve all the previous Year Question asked on Metabolism of Chylomicron

Module Below Start Quiz

Cholesterol Synthesis

Cholesterol synthesis

Q. 1

The major step of regulation of cholesterol synthesis is:

 A

Cyclization of squalene to lanosterol

 B

3-hydroxy-3-methylglutaryl-CoA synthase

 C

3-hydroxy-3-methylglutaryl-CoA lyase

 D

3-hydroxy-3-methylglutaryl-CoA reductase

Q. 1

The major step of regulation of cholesterol synthesis is:

 A

Cyclization of squalene to lanosterol

 B

3-hydroxy-3-methylglutaryl-CoA synthase

 C

3-hydroxy-3-methylglutaryl-CoA lyase

 D

3-hydroxy-3-methylglutaryl-CoA reductase

Ans. D

Explanation:

Cholesterol is obtained from the diet as well as by de novo synthesis.

Although many cells can synthesize cholesterol, the liver is the major site of its production.

The rate of cholesterol production is highly responsive to feedback inhibition from both dietary cholesterol and synthesized cholesterol.

Feedback regulation is mediated by changes in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase.  

This enzyme is the first committed step in the production of cholesterol from acetyl-CoA.

3-Hydroxy-3-methylflutaryl-CoA, the substrate of the reductase, also can be synthesized into the ketone by acetoacetate by the action of 3-hydroxy-3-methylglutaryl-CoA lyase

Ref: Essentials of Medical Biochemistry; With Clinical Cases, 1st Ed, page 215


Q. 2

The first step in synthesis of steroids is derived from the cleavage of cholesterol. What is the enzyme responsible for the cleavage of 20,22-dehydrocholesterol to pregnenolone?

 A

Delta 5-3 beta-hydroxysteroid dehydrogenase (3B – HSD)

 B

HMG-CoA reductase

 C

Aromatase

 D

17 alpha-hydroxylase

Q. 2

The first step in synthesis of steroids is derived from the cleavage of cholesterol. What is the enzyme responsible for the cleavage of 20,22-dehydrocholesterol to pregnenolone?

 A

Delta 5-3 beta-hydroxysteroid dehydrogenase (3B – HSD)

 B

HMG-CoA reductase

 C

Aromatase

 D

17 alpha-hydroxylase

Ans. A

Explanation:

The enzyme responsible for the cleavage of 20,22-dehydrocholesterol to pregnenolone is termed Delta 5-3 beta-hydroxysteroid dehydrogenase ( 3B HSD). Pregnenolone is a precursor to progesterone. Conversion to progesterone is necessary for eventual synthesis of testosterone and estrogen. Although there are different enzymes for their production, progesterone converted from cholesterol is of primary importance.
 
Ref: Weil P. (2011). Chapter 41. The Diversity of the Endocrine System. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.
 

Q. 3

Which of the following enzymes is common to the synthesis of cholesterol and ketone bodies:

 A

HMG -Co-A Reductase

 B

HMG-Co-A Lyase

 C

HMG-Co-A Synthase

 D

Thiokinase

Q. 3

Which of the following enzymes is common to the synthesis of cholesterol and ketone bodies:

 A

HMG -Co-A Reductase

 B

HMG-Co-A Lyase

 C

HMG-Co-A Synthase

 D

Thiokinase

Ans. C

Explanation:

C i.e. HMG-Co-A Synthase

Quiz In Between


Q. 4

Which of the following blocks DNA replication with getting incorporated in DNA strand:

 A

Cytarabine

 B

Nalidixic acid

 C

Ciprofloxacin

 D

Paclitaxel

Q. 4

Which of the following blocks DNA replication with getting incorporated in DNA strand:

 A

Cytarabine

 B

Nalidixic acid

 C

Ciprofloxacin

 D

Paclitaxel

Ans. A

Explanation:

A i.e. Cytarabine


Q. 5

Cholesterol is synthesized from:

 A

Acetyl CoA

 B

Alpha-ketoglutarate

 C

Glutaric acid

 D

Oxalate

Q. 5

Cholesterol is synthesized from:

 A

Acetyl CoA

 B

Alpha-ketoglutarate

 C

Glutaric acid

 D

Oxalate

Ans. A

Explanation:

Q. 6

Cholesterol is:        

 

 A

Tocopherol

 B

Lipoprotein

 C

Steroid

 D

Lipopolysacchride

Q. 6

Cholesterol is:        

 

 A

Tocopherol

 B

Lipoprotein

 C

Steroid

 D

Lipopolysacchride

Ans. C

Explanation:

 

Cholesterol is an amphipathic lipid and is an important structural component of membranes and of the outer layer of plasma lipoproteins.

It is mainly synthesized in many tissues from Acetyl-CoA and is the precursor of all other steroids in the body, including corticosteroids, sex hormones, bile acids, and vitamin D.

Quiz In Between


Q. 7

Cholesterol is not a precursor of:

 A

Bile acid

 B

Bile pigment

 C

Vitamin D

 D

Sex hormones

Q. 7

Cholesterol is not a precursor of:

 A

Bile acid

 B

Bile pigment

 C

Vitamin D

 D

Sex hormones

Ans. B

Explanation:

 

Cholesterol is the precursor of bile acids [Bile contains bile salts (conjugated bile acids), which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K].

 


Q. 8

Mineral required for cholesterol biosynthesis ‑

 A

Fe

 B

Mn

 C

Mg

 D

Cu

Q. 8

Mineral required for cholesterol biosynthesis ‑

 A

Fe

 B

Mn

 C

Mg

 D

Cu

Ans. C

Explanation:

 

Mg is required in stage 2 of cholesterol synthesis.

Biosynthesis (De Novo Synthesis) of cholesterol

  • The liver is the major site for cholesterol biosynthesis. Some cholesterol is also synthesized in intestine adre‑nal cortex, gonads and skin. The microsomal (smooth endoplasmic reticulum) and cytosol fraction of cell is responsible fir cholesterol synthesis; However most of the reactions in synthesis occurs in cytosol.
  • Cholesterol is a C-27 compound. All 27-carbon atoms of cholesterol are derived from a single precursor, i.e. acetyl-CoA (activated acetate).
  • First two molecules of acetyl-CoA condense to form acetoacetyl-CoA. Next, a third molecule of acetyl- CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Then HMG-CoA is converted to mevalonate by HMG-CoA reductase, the key regulatory enzyme of cholesterol synthesis.

Q. 9

Rate limiting step in cholesterol synthesis –

 A

HMG CoA reductase 

 B

HMG CoA synthase 

 C

Mevalonate kinase

 D

Squalene synthetase

Q. 9

Rate limiting step in cholesterol synthesis –

 A

HMG CoA reductase 

 B

HMG CoA synthase 

 C

Mevalonate kinase

 D

Squalene synthetase

Ans. A

Explanation:

Ans. is ‘a’ i.e., HMG Co A reductase

Reactions Rate limiting enzymes 
Glycolysis Phosphofructokinase 
Glycogen synthesis  Glycogen synthetase 

Glycogenolysis

Glycogen phosphorylase 

TCA cycle

Isocitrate dehydrogenase 
Fatty acid synthesis  Acetyl CoA carboxylase 
Cholesterol synthesis  HMG CoA reductase HMG 
Ketone body synthesis CoA synthase 
Bile acid synthesis  7-a-hydroxylase
Catecholamine synthesis  Tyrosine hydroxylase 
Urea synthesis

Carbamoyl transferase

Quiz In Between



Cholesterol Synthesis

CHOLESTEROL SYNTHESIS


CHOLESTEROL SYNTHESIS

  • Cholesterol is the major sterol in humans.
  • Major component in plasma membrane.

Synthesis of Cholesterol

  • Major sites- Liver, adrenal cortex, testis, ovaries and intestine.
  • Cell organelle- endoplasmic reticulum and cytoplasm
  • First material is Acetyl CoA.
  • Acetyl- CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)
  • Then HMG-CoA is converted to mevalonate by HMG-CoA reductase, (the key regulatory enzyme of cholesterol synthesis)

Exam Important

  • Cholesterol is the major sterol in humans.
  • Major sites- Liver, adrenal cortex, testis, ovaries and intestine.
  • Cell organelle- endoplasmic reticulum and cytoplasm
  • First material is Acetyl CoA.
  • Acetyl- CoA condenses with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)
  • Then HMG-CoA is converted to mevalonate by HMG-CoA reductase, (the key regulatory enzyme of cholesterol synthesis)
Don’t Forget to Solve all the previous Year Question asked on CHOLESTEROL SYNTHESIS

Module Below Start Quiz

Metabolism of HDL

Metabolism of HDL

Q. 1

Which of the following statements about High Density Lipoprotein (HDL) is false:

 A

HDL increases oxidation of LDL

 B

HDL reduces foam cell production by LDL

 C

HDL is the best predictor of CAD

 D

HDL helps to clear lipids from atheromas

Q. 1

Which of the following statements about High Density Lipoprotein (HDL) is false:

 A

HDL increases oxidation of LDL

 B

HDL reduces foam cell production by LDL

 C

HDL is the best predictor of CAD

 D

HDL helps to clear lipids from atheromas

Ans. A

Explanation:

HDL prevent oxidation of LDL in complex in vitro models as a result HDL function as a naturally acting antioxidant which protect vessel wall from oxidative damage and resulting atherogenesis.

Ref: Current Pharmaceutical Design, Page 6.


Q. 2

Good cholesterol found in:

 A

HDL

 B

LDL

 C

VLDL

 D

IDL

Q. 2

Good cholesterol found in:

 A

HDL

 B

LDL

 C

VLDL

 D

IDL

Ans. A

Explanation:

A i.e. HDL

  • HDL contains good cholesterolQ. So there is an inverse relation between HDL (HDL2) concentrations and coronoary heart disease. This is consistent with the function of HDL in reverse cholesterol transport.
  • Diseases (eg. diabetes mellitus, lipid nephrosis, hypothyroidism and other considtions of hyperlipedimea) in which prolonged elevations of VLDL, IDL, LCD or chulomicron remnants in blood are often accompanied by premature or severe atherosclerosis. This makes LDL : HDL cholesterol ratio a good predective parameter for atherosclerosis & coronary heart disease.

Q. 3

Reverse cholesterol transport is mediated by

 A

HDL

 B

VLDL

 C

LDL

 D

IDL

Q. 3

Reverse cholesterol transport is mediated by

 A

HDL

 B

VLDL

 C

LDL

 D

IDL

Ans. A

Explanation:

Ans. is ‘a’ i.e., HDL

Reverse cholesterol transport

  • All nucleated cells in different tissues synthesize cholesterol, but the excretion of cholesterol is mainly by liver in the bile or by enterocytes in gut lumen.
  • So, cholesterol must be transported from peripheral tissue to liver for excretion.

o This is facilitated by HDL and is called reverse cholesterol transport because it transports the cholesterol in reverse direction to that is transported from liver to peripheral tissues through VLDL                        LDL cycle. Process

o HDL is synthesized in liver and small intestine.

o Nascent HDL contain phospholipids and unesterified cholesterol and Apo-A, C, E.

  • This nascent HDL is secreted into circulation where it acquires additional unesterified cholesterol from peripheral tissues.

o Within the HDL particle, the cholesterol is esterified by lecithin – cholesterol acetyltransferase (LCAT) to form cholesteryl ester and additional lipid are transported to HDL from VLDL and chylomicrons.

o There are two pathway by which this cholesterol is transported to liver.


Q. 4

All are bad cholesterol except:    

 A

HDL

 B

LDL

 C

VLDL

 D

IDL

Q. 4

All are bad cholesterol except:    

 A

HDL

 B

LDL

 C

VLDL

 D

IDL

Ans. A

Explanation:

 

HDL can remove cholesterol from atheroma within arteries and transport it back to the liver for excretion or re-utilization, which is the main reason why HDL-bound cholesterol is sometimes called “good cholesterol”, or HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases, and low HDL cholesterol levels (less than 40 mg/ dL or about 1mmol/L) increase the risk for heart disease.

Cholesterol contained in HDL particles is considered beneficial for the cardiovascular health, in contrast to “bad” LDL cholesterol.

Quiz In Between


Q. 5

Lipoprotein involved in reverse cholesterol transport‑

 A

LDL

 B

VLDL

 C

IDL

 D

HDL

Q. 5

Lipoprotein involved in reverse cholesterol transport‑

 A

LDL

 B

VLDL

 C

IDL

 D

HDL

Ans. D

Explanation:

 

The HDL particles are referred to as scavengers because their primary role is to remove free (unesterified) cholesterol from the extrahepatic tissues.

HDL particles transport cholesterol from extrahepatic tissues to liver (i.e. reverse cholesterol transport) which is then excreted through bile.

Reverse cholesterol transport

All nucleated cells in different tissues synthesize cholesterol, but the excretion of cholesterol is mainly by liver in the bile or by enterocytes in gut lumen. So, cholesterol must be transported from peripheral tissue to liver for excretion. This is facilitated by HDL and is called reverse cholesterol transport because it transports the cholesterol in reverse direction to that is transported from liver to peripheral tissues through VLDL → LDL cycle.

Process

HDL is synthesized in liver and small intestine. Nascent HDL contain phospholipids and unesterified cholesterol and Apo-A, C, E. This nascent HDL is secreted into circulation where it acquires additional unesterified cholesterol from peripheral tissues. Within the HDL particle, the cholesterol is esterified by lecithin – cholesterol acetyltransferase (LCAT) to form cholesteryl ester and additional lipid are transported to HDL from VLDL and chylomicrons. Apo-A1 activates LCAT.


Q. 6

Lipoprotein associated with carrying cholesterol from peripheral tissues to liver is ‑

 A

 HDL

 B

LDL

 C

VLDL

 D

IDL

Q. 6

Lipoprotein associated with carrying cholesterol from peripheral tissues to liver is ‑

 A

 HDL

 B

LDL

 C

VLDL

 D

IDL

Ans. A

Explanation:

 

HDL particles transport cholesterol from extrahepatic tissues to liver (i.e. reverse cholesterol transport) which is then excreted through bile.


Q. 7

Cholesteryl ester transfer protein transport cholesterol from HDL to ‑

 A

VLDL

 B

IDL

 C

LDL

 D

Chylomicrons

Q. 7

Cholesteryl ester transfer protein transport cholesterol from HDL to ‑

 A

VLDL

 B

IDL

 C

LDL

 D

Chylomicrons

Ans. A

Explanation:

 

Cholesteryl ester is tranfered from HDL to VLDL and chylomicrons in exchange with triglyceride by the cholesteryl ester transfer protein (CETP).


Q. 8

Lipoprotein associated with carrying cholesterol from periphery tissues to liver is ‑

 A

HDL

 B

LDL

 C

VLDL

 D

1DL

Q. 8

Lipoprotein associated with carrying cholesterol from periphery tissues to liver is ‑

 A

HDL

 B

LDL

 C

VLDL

 D

1DL

Ans. A

Explanation:

Ans. is ‘a’ i.e., HDL 

Quiz In Between



Metabolism of HDL

Metabolism of HDL


HDL METABOLISM

  • Nascent HDL is synthesized and secreted from intestine and liver.
  • Nascent HDL contain phospholipids, cholesterol and Apo A.
  • Lecithin cholesterol Acyl Transferase (LCAT) esterified by cholesterol.
  • Apo- A- I activates LCAT.

Cholesterol is transported to liver in 2 ways-

  1. Indirect pathway Cholestryl ester is transferred from HDL to VLDL and chylomicrons by cholestryl ester transfer protein (CETP)à Liver
  2. Direct pathway HDL cholesterol by liver via scavenger receptors.
  • HDL particles are referred to as scavangers.
  • The level of HDL in serum is inversely related to the incidence of MI.
  • HDL is cardioprotective and anti- atherogenic is referred to good cholesterol.
  • HDL- Cholesterol appears to be the best independent predictor of coronary artery disease.
  • HDL collects excess cholesterol iron tissues and transport it to liver and steroidogenic tissues. This is called Reverse cholesterol transport.

Exam Important

  • Nascent HDL is synthesized and secreted from intestine and liver.
  • Nascent HDL contain phospholipids, cholesterol and Apo A.
  • Lecithin cholesterol Acyl Transferase (LCAT) esterified by cholesterol.
  • Apo- A- I activates LCAT.

Cholesterol is transported to liver in 2 ways-

  1. Indirect pathwayCholestryl ester is transferred from HDL to VLDL and chylomicrons by cholestryl ester transfer protein (CETP)à Liver
  2. Direct pathway– HDL cholesterol by liver via scavenger receptors.
  • HDL particles are referred to as scavangers.
  • The level of HDL in serum is inversely related to the incidence of MI.
  • HDL is cardioprotective and anti- atherogenic is referred to good cholesterol.
  • HDL- Cholesterol appears to be the best independent predictor of coronary artery disease.
  • HDL collects excess cholesterol iron tissues and transport it to liver and steroidogenic tissues. This is called Reverse cholesterol transport.
Don’t Forget to Solve all the previous Year Question asked on Metabolism of HDL

Module Below Start Quiz

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