Question

Explain how Niacin can be used to reduce a ketone. Please provide a mechanism. Draw by hand

Explain how a cell ubiquitinates a protein and provide two possible reasonings for doing so.

Explain how high levels of amino acids can act as feedback inhibitors.

Answer 1

Niacin can be used as a cofactor for reduction of ketones using biocatalysts. Dehydrogenases or Carbonyl Reductases (CRED) can be used for the reduction of ketones, to chiral alcohols.

Ubiquitin is a 76-amino-acid polypeptide that is highly conserved in all eukaryotes. Proteins are marked for degradation by the attachment of ubiquitin to the amino group of the side chain of a lysine residue. Ubiquitination is a multistep process. First, ubiquitin is activated by being attached to the ubiquitin-activating enzyme, E1. The ubiquitin is then transferred to a second enzyme, called ubiquitin-conjugating enzyme (E2). The final transfer of ubiquitin to the target protein is then mediated by a third enzyme, called ubiquitin ligase or E3, which is responsible for the selective recognition of appropriate substrate proteins. This is how multiple ubiquitin molecules are added to the protein forming polyubiquitin chain. Such polyubiquinated proteins are recognized and degraded by multi-subunit protease complex called proteasome. This is done if -

1. Faulty or damaged proteins are recognized.

2. Short-lived proteins, many of which are regulatory proteins, whose actions are controlled in part by rapid synthesis and degradation.

High levels of amino acid production acts as feedback inhibitors. Most of the pathways of amino acid biosynthesis are regulated by feedback inhibition, in which the first committed step is allosterically inhibited by the final product. Branched pathways require extensive interaction among the branches that includes both negative and positive regulation. The regulation of glutamine synthetase from E. coli demonstrates a cumulative feedback inhibition and control by a cascade of reversible covalent modifications.