Thursday, August 23, 2012

Functions of Biotin

Q.1- Justify the statement – ‘Biotin Is a Coenzyme of Carboxylase Enzymes’.
Answer- Biotin functions to transfer carbon dioxide in a small number of carboxylation reactions Acetyl-CoA, Pyruvate, Propionyl-CoA, and Methylcrotonyl-CoA carboxylases). Biotin is attached at the active site of carboxylases.
A holocarboxylase synthetase catalyzes the transfer of biotin onto a lysine residue of the apo enzyme to form the biocytin residue of the holoenzyme. Bicarbonate as a source of CO2 is required in the initial reaction for the carboxylation (figure -1).


Figure- 1-(A) showing the attachment of biotin to the enzyme (B) showing the general reaction for biotin dependent carboxylases
The reactive intermediate is 1 N carboxy biocytin, formed from bicarbonate in an ATP-dependent reaction. The carboxy group is then transferred to the substrate for carboxylation.
1) Role of Biotin in carboxylation reactions
Each Biotin dependent carboxylase catalyzes an essential metabolic reaction;
Acetyl-CoA carboxylase (ACC) catalyzes the binding of bicarbonate to acetyl-CoA to form malonyl-CoA (Figure-2). Malonyl-CoA is required for the synthesis of fatty acids. The former is crucial in cytosolic fatty acid synthesis, and the latter functions in regulating mitochondrial fatty acid oxidation.

Figure-2 Shows carboxylation of Acetyl co A to form Malonyl co A,the first and the rate limiting step in fatty acid synthesis
Pyruvate carboxylase is a critical enzyme in gluconeogenesis—the formation of glucose from sources other than carbohydrates, for example, amino acids. Oxaloacetate formed from pyruvate can be utilized in many other ways depending upon the need of the cell (Figure-3)


Figure-3 showing the carboxylation of pyruvate to Oxaloacetate , the first step of gluconeogenesis.
Propionyl-CoA carboxylase catalyzes essential steps in the metabolism of certain amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules). 


Figure- 4-showing the fate of Propionyl co A
Propionyl co A is converted first to D- Methyl malonyl co A  and then to its L isomer, ultimately to succinyl co A for complete utilization in the TCA cycle (Figure-4).
Anaplerotic reactions catalyzed by biotin dependent pyruvate carboxylase (PC) and Propionyl-coenzyme A carboxylase (PCC) regenerate oxaloacetate for the citric acid cycle
Methylcrotonyl-CoA carboxylase catalyzes an essential step in the catabolism of leucine, an essential amino acid.
2) Role of Biotin in cell cycle regulation
Biotin also has a role in regulation of the cell cycle, acting to biotinylate key nuclear proteins such as histones and other proteins.
Histone biotinylation
Histones are proteins that bind to DNA and package it into compact structures to form nucleosomes—integral structural components of chromosomes. The compact packaging of DNA must be relaxed somewhat for DNA replication and transcription to occur. Modification of histones through the attachment of acetyl or methyl groups (acetylation or methylation) has been shown to affect the structure of histones, thereby affecting replication and transcription of DNA. Mounting evidences indicate that biotinylation of histones plays a role in regulating DNA replication and transcription as well as cellular proliferation and other cellular responses (Figure-5)

Figure-5- showing the role of biotin in the body. Holocarboxylase synthetase (HCS) catalyzes biotinylation of the apoenzyme while Biotinidase catalyzes the release of biotin from histones and from the peptide products of carboxylase breakdown.
Although the major role of biotin is as a coenzyme with carboxylase enzymes as mentioned above, Biotin also plays a special role in enabling the body to use blood glucose as a major source of energy for body fluids. It also activates protein/amino acid metabolism in the hair roots and fingernail cells. Due to its beneficial effects for hair, skin and nails, biotin is also known as the “beauty vitamin”.
Q.2-What is egg white injury ?
Raw egg whites contain Avidin, a glycoprotein that strongly binds with biotin and prevents its absorption. once a biotin-avidin complex forms, the bond is essentially irreversible; the biotin-avidin complex is not broken during passage of the food bolus through the stomach and intestines. As a result, biotin is not liberated from food, and the biotin-avidin complex is lost in the feces. Thus, the ingestion of large quantities of raw egg white over a long period can result in a biotin deficiency.
Cooking egg white denatures avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin.

Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123, ehab fathy aboueladab
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