Clinical biochemistry and advanced assessment in nutrition - Assignment Example

Structurally and functionally, pyruvate dehydrogenase complex is closely related to oxoglutarate dehydrogenase. On the other hand, branched –chain ketoacid dehydrogenease complex (BCKDC) is another critically significant enzyme complex that plays a critical role in the normal breakwdown of amino acids by catalyzing the oxidative decarboxylation of the branched short chain alpha ketoacids. In terms of their functionality, one of the most important similarities between the two enzymes is that just like the Pyruvate dehydrogenase complex, (BCKDC) is also an intermitochondiarial enzyme complex that is primarily regulated by covalent modification.

Additionally, much like Pyruvate dehydrogenase complex (PDC), the branched –chain ketoacid dehydrogenease complex (BCKDC) is also comprised of the three components namely the oxoglutarate dehydrogenase, dihydrolipolyl succinytransferase and dihydrolipoyl dehydrogenase. With regard to the differences between the two enzyme complexes, the deficiency of the Pyruvate dehydrogenase complex is normally caused by mutations in any of the cofactors or enzymes and the main clinical finding is usually lactic acidosis.

However, unlike PDC, branched –chain ketoacid dehydrogenease complex is primarily concerned with the catabolism of branched amino acids such as valine, luecine and isoleucine. As a result, the deficiency of branched –chain ketoacid dehydrogenease complex is normally associated with the development of maple syrup urine disease as well as a number of other related medical problems. Accumulation for branched chain keto-acids is widely believed to be one of the potential causes of neurological features of MSUD through the induction of oxidative stress in the glioma cells.

Lastly, when there is insufficient activity of Pyruvate dehydrogenase complex, the organic acids that are usually elevated is primarily lactic acid while the insufficient activity of branched –chain ketoacid dehydrogenease complex normally result in the elevation of three organic acids namely: 2-oxoisocaproic acid derived from leucine, 2-oxoisovaleric acid derived from valine and 2-oxo-3-methylvaleric acid derived from isoleucine. How Peroxisomes are activated (PPAR system Fatty acid oxidation is an important metabolic pathway that normally results in the mitochondrial breakdown of long chain acyl-CoA to acetyl-CoA.

The many steps involved in the process are generally regulated by PPARs at the transcriptional level. Peroxizomes usually work by proliferating or decreasing in response to lipids, toxicants, hormones or drugs that bind to bind to PPAR. On the other hand, the activation of peroxizomes is achieved when the PPAR suppress the gene transcription through small additions of dietary PUEFAs. Fig 1: Oxidation of fatty acids pathway How does biotin relate to multiple carboxylase deficiency (MCD)? What are the symptoms and organic acid markers of biotin deficiency?

Biotin is an important B-complex vitamin that is primarily obtained from food, but is also synthesized by certain microorganisms such as bifidobacteria in the human gut. Biotin is closely relate with multiple carboxylase deficiency (MCD) in that the heritable disorders of biotin metabolism usually lead to MCD condition that is characterized by deficiency in the activities of various diotin