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Petition Letter: To begin, I would like to discuss specifically the biochemical basis of disease section. I believe that I explained the healthy and diseased states in my paper well. Beginning from ??In a healthy individual, BTD cleaves biotin depicted in Figure 12 ?? also known as coenzyme R, vitamin H, and vitamin B7 ?? from biocytin or biotinyl-peptides. This produces free biotin and lysine and restores free biotin to proceed as a cofactor, increasing enzymatic activity2. Biotinidase is also important for making biotin bioavailable from bound dietary sources.7 Several food sources contain biotin including raw egg yolk, milk, organ meats, and leafy green vegetables2. Biotin is a cofactor, specifically a prosthetic group. As a cofactor, biotin is part of many different processes... Biotin-dependent carboxylases are crucial components utilized in intracellular processes through which nutritive material is transformed into cellular components as outlined in Figure 2. This process is described as intermediary metabolism. The carboxylases aid in the production of fats through fatty acid synthesis, gluconeogenesis, and amino acid catabolism.? I continued to explain in further detail which is outlined in my paper. Furthermore, I explained the causes of the diseased state and how it affects the enzyme at the biochemical level All mutations lead to enzymatic activities with less than 10% of mean normal serum enzyme activity causing profound BD, however, partial BD is caused by a mutation resulting in the enzyme having 10-30% of mean normal serum BTD activity.4 All types of mutations have been found to cause BD including missense, nonsense, single and multiple nucleotide deletions, single and multiple nucleotide insertions, cryptic splice site mutations, and compound allelic mutations.5 An example of a mutation of the BTD gene is a single amino acid substitution involving a cysteine residue called C423R.6 The substitution replaces cysteine with another amino acid which can either alter enzyme folding as the original cysteine residue is involved in disulfide bonding or it could disrupt the free sulfhydryl at the active site of the enzyme... With biotinidase deficiency, the four human carboxylases are predominantly affected: ACC, PCC, MCC, and PC. Following this paragraph, I dive into the effects of BD on each of the carboxylases and the pathway it affects leading to symptoms, for example, The conversion of propionyl-CoA to D-methylmalonyl-CoA that is catalyzed by PCC requires biotin as a coenzyme.14 Deficiency of PCC activity due to BD causes an accumulation of propionyl-CoA ?? a catabolic product of the amino acids methionine, valine, isoleucine, and threonine ?? and an accumulation of D-methylmalonyl-CoA leading to propionic acidemia, hypotonia, hyperammonemia, ketoacidosis... I explained how symptoms result from deficiencies in the human carboxylases which cause accumulation of substrate among other consequences leading to symptoms ?? formatting it similarly to ??spotlight on disease? sections in our modules.

The next section I would like to gain insight to is the diagnosis and treatment section. In my paper I discussed genetic testing and other diagnosis methods stating that ??To establish the child??s enzyme status after transfusion, the BTD activities of their parents can be measured through genetic testing. If the two parents??. I additionally explained how a positive and negative result is determined 'Samples from negative infants are purple in colour, however, infants that are positive have straw-coloured samples. In addition, for the treatment I explained how free biotin restores the cycle and the human carboxylases, improving symptoms This therapy uses free biotin, as bound biotin placed within an oral multivitamin supplement would not effectively treat the deficiency.2 Oral biotin augments the amount of free biotin entering the cycle leading to the improved function of the biotin cycle. As a result, the activities of the four human carboxylases affected by BD are increased...Individuals with BD should avoid raw eggs as they contain an egg-white protein known as avidin. This protein will bind to biotin and consequently reduce its bioavailability In this section I explain the symptoms that are improved from the treatment. I provided an additional few treatments for symptoms that could not be treated with free biotin as well . Symptoms such as spasticity and dystonia that are related to inborn errors of metabolism have been treated with intrathecal baclofen and neurotoxins.

The last section I would like to discuss is the writing and grammar section. I adapted my figures with a caption and by referencing them in the paper, for example,Biotin-dependent carboxylases are crucial components utilized in intracellular processes through which nutritive material is transformed into cellular components as outlined in Figure 2 and Figure 2. A Visual of the biotin cycle including the four human carboxylases. I believe I separated my paper in an organized manner that flowed logically (healthy, diseased, symptoms) as well. I began by explaining the biochemical basiss of the diseased, how a healthy individual would function, followed by symptoms resulting from the affected pathways.

I would like to gain insight into how marks were lost and possibly reward marks to these sections.