Tag: Carnitine

Carnitine

Carnitine


INTRODUCTION:

  • Carnitine is a quaternary ammonium compound.
  • In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (fats) for the generation of metabolic energy
  • It is widely available as a nutritional supplement
  • Carnitine exists in two stereo isomers: Its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive

BIOSYNTHESIS:

  • In animals, the biosynthesis of carnitine occurs primarily in the liver and kidneys from the amino acids lysine (via trimethyllysine) and methionine
  • It is a method for the endogenous production of L-carnitine, a molecule that is essential for energy metabolism
  • Amino acid used in Carnitine synthesis is Lysine & Methionine

Utilization of carnitine?Carnitine transports long-chain acyl groupsfrom fatty acids into the mitochondrial matrix,so t...

 UTILIZATION:
  • Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle
  • Fatty acids must be activated before binding to the carnitine molecule to form ‘acylcarnitine’. 
  • The free fatty acid in the cytosol is attached with a thioester bond to coenzyme A (CoA). This reaction is catalyzed by the enzyme fatty acyl-CoAsynthetase
  • The acyl group on CoA can now be transferred to carnitine and the resulting acylcarnitine transported into the mitochondrial matrix. This occurs via a series of similar steps
  • Acyl CoA is transferred to the hydroxyl group of carnitine by carnitine acyltransferase I (palmitoyltransferase) located on the outer mitochondrial membrane
  • Acylcarnitine is shuttled inside by a carnitine-acylcarnitine translocase
  • Acylcarnitine is converted to acyl CoA by carnitine acyltransferase II (palmitoyltransferase) located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol.
  • Carnitine acyltransferase I undergoes allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, to prevent futile cycling between β-oxidation and fatty acid synthesis.
  • Carnitine palmitoyl transferase I is present in outer mitochondrial membrane & Carnitine palmitoyl trasferase II in inner  mitochondrial membrane

USES:

  • Heart conditions
  • Kidney disease and dialysis
  • Effect in male infertility
  • As a weight loss supplement:Carnitine is essential for transfer of fatty acids across mitochondrial membrane 
  • As an antidote in valproic acid poisoning
  • To improve symptoms in moderate asthmatics
  • To improve fatigue resulting from ifosfamide cancer chemotherapy
  • To treat symptoms of hyperthyroidism
Exam Question
 
  • Amino acid used in Carnitine synthesis is Lysine
  • The substance essential for transfer of fatty acids across mitochondrial membrane is Carnitine 
  • Carnitine is synthesised from Methionine
  • Carnitine  is involved in transport of long chain acyl-CoA in mitochondria
  • Hepatotoxicity caused by valproate can be prevented by Carnitine  
  • Carnitine palmitoyl transferase I is present in outer mitochondrial membrane & Carnitine palmitoyl trasferase II in inner  mitochondrial membrane
Don’t Forget to Solve all the previous Year Question asked on Carnitine

Carnitine

Carnitine

Q. 1

Amino acid used in Carnitine synthesis is which of the following?

 A

Alanine

 B

Lysine

 C

Arginine

 D

Tyrosine

Q. 1

Amino acid used in Carnitine synthesis is which of the following?

 A

Alanine

 B

Lysine

 C

Arginine

 D

Tyrosine

Ans. B

Explanation:

Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely available as a nutritional supplement.


Q. 2

Carnitine-acylcarnitine translocase acts as an inner membrane exchange transporter. Carnitine is synthesized from:

 A

Alanine

 B

Arginine

 C

Lysine

 D

Glycine

Q. 2

Carnitine-acylcarnitine translocase acts as an inner membrane exchange transporter. Carnitine is synthesized from:

 A

Alanine

 B

Arginine

 C

Lysine

 D

Glycine

Ans. C

Explanation:

Levocarnitine (L-carnitine):

  • It is an endogenous carboxylic acid that facilitates transport of long-chain fatty acids into mitochondria for beta-oxidation and prevents intracellular accumulation of toxic acyl-CoA. 
  • L-Carnitine is ubiquitous in diets rich in meats and dairy products and is also synthesized in the body from the amino acids lysine and methionine.
  • Valproic acid causes carnitine deficiency, resulting in mitochondrial dysfunction. 
  • Primary defects of carnitine transport may manifest as Reyes syndrome, cardiomyopathy, or skeletal myopathy with hypotonia.
 
Ref: Thomas J.A., Van Hove J.L. (2012). Chapter 36. Inborn Errors of Metabolism. In W.W. Hay, Jr., M.J. Levin, R.R. Deterding, J.J. Ross, J.M. Sondheimer (Eds), CURRENT Diagnosis & Treatment: Pediatrics, 21e.

Q. 3

The substance essential for transfer of fatty acids across mitochondrial membrane:

 A

Cera tine

 B

Ceratinine

 C

Carnitine

 D

Coenyzme A

Q. 3

The substance essential for transfer of fatty acids across mitochondrial membrane:

 A

Cera tine

 B

Ceratinine

 C

Carnitine

 D

Coenyzme A

Ans. C

Explanation:

C i.e. Carnitine


Q. 4

All are true about 0-oxidation except:

 A

Activation of FA is a must

 B

Carnitine palmitoyl transferase I is present in outer mitochondrial membrane

 C

Carnitine palmitoyl trasferase II is present in mitochondrial matrix

 D

FA activation requires 2ATP.

Q. 4

All are true about 0-oxidation except:

 A

Activation of FA is a must

 B

Carnitine palmitoyl transferase I is present in outer mitochondrial membrane

 C

Carnitine palmitoyl trasferase II is present in mitochondrial matrix

 D

FA activation requires 2ATP.

Ans. C

Explanation:

C i.e. Carnitine palmitoyl trasf erase II is present in mitochondrial matrix

Long chain activated fatty acid penetrate the inner mitochondria( membrane only in combination with carnitineQ. Carnitine, a carrier molecule, acts like a ferry boat and transport long chain acyl- CoA across mitochondiral membrane otherwise inner mitochondrial membrane is impermeable to acyl -CoA.


Q. 5

Hepatotoxicity caused by valproate can be prevented by-

 A

Zinc

 B

Carnitine

 C

Pyridoxine

 D

Vit K

Q. 5

Hepatotoxicity caused by valproate can be prevented by-

 A

Zinc

 B

Carnitine

 C

Pyridoxine

 D

Vit K

Ans. B

Explanation:

Ans. is ‘b’ i.e., Carnitine

o Valprate is a hepatotoxic drug.

o Hepatotoxicity is due to its metabolite 4-pantenoic acid.

o Valprate hepatotoxicity is more common in persons with mitochondrial enzyme deficiency and may be ameliorated by administration of Carnitine, which valproate therapy can deplete.


Q. 6

Which is involved in transport of long chain acyl-CoA in mitochondria?    

 A

Ornithine

 B

Xanthine

 C

Carnitine

 D

Albumin

Q. 6

Which is involved in transport of long chain acyl-CoA in mitochondria?    

 A

Ornithine

 B

Xanthine

 C

Carnitine

 D

Albumin

Ans. C

Explanation:

 

In humans carnitine is synthesized from protein-derived trimethyllysine in liver, brain and kidney.

Muscles take up carnitine from the blood in an exchange-diffusion process with endogenous deoxycarnitine, the immediate precursor of carnitine.

Besides catalysing the transport of long-chain acyl groups in mitochondria, carnitine is necessary for the export of intramitochondrially produced short-chain acyl residues and for the trapping and the elimination of unphysiological compounds (benzoic, pivalic, valproic acids etc.).


Q. 7

Role of carnitine in lipid metabolism ‑

 A

Catalyzation of the cyclization sequence

 B

Essential for extracellular transfer of fatty acids

 C

Essential for biosynthesis of fatty acids

 D

Transfer of activated long chain FFA into mitochondria

Q. 7

Role of carnitine in lipid metabolism ‑

 A

Catalyzation of the cyclization sequence

 B

Essential for extracellular transfer of fatty acids

 C

Essential for biosynthesis of fatty acids

 D

Transfer of activated long chain FFA into mitochondria

Ans. D

Explanation:

Ans. is ‘d’ i.e., Transfer of activated long chain FFA into mitochondria

Activated long chain fatty acid (acyl CoA) cannot penetrate inner mitochondria! membrane.

Acyl group of acyl CoA is transferred to carnitine, resulting in formation of acylcarnitine.

Acylcarnitine is then transported across the inner mitochondria! membrane into the mitochondria! matrix by translocase.

Once inside the mitochondrion, acyl group of acylcarnitine is transferred back to CoA, resulting in formation of acyl-CoA which undergoes 13-oxidation.


Q. 8

Carnitine is synthesised from ‑

 A

Methionine

 B

Arginine

 C

Histidine

 D

Choline

Q. 8

Carnitine is synthesised from ‑

 A

Methionine

 B

Arginine

 C

Histidine

 D

Choline

Ans. A

Explanation:

 

Carnitine is synthesized from amino acids lysine and methionine.



Malcare WordPress Security