Deduce the likely enzyme deficiency causing the infant's condition and explain how this deficiency can cause his symptoms. How might you treat this disorder
The lack of the denaturase enzyme results in a build up of unreduced LFA and a increased request of caritine to transport the accumulating waste products. The caritine is then becoming acylated with the LFA which results in low serum caritine and a disruption of fatty acid metabolism overall.
2. Wakil's pioneering studies on the synthesis of fatty acids included the crucial observation that bicarbonate was required for the synthesis of palmitoyl CoA. He was surprised to find that very low levels of bicarbonate could sustain palmitate biosynthesis and that there is no correlation between the amount of bicarbonate required and the amount of palmitate produced. Explain these observations and describe how radiolabelled bicarbonate could be used to support your explanation.
The following reactiom is the accepted mechanism for producing the long chain fatty acid palmitoyl-CoA. When acetyl coenzyme A, malonyl coenzyme A and reduced triphospopyridine nucleotide (TPNH) are used as substrates palmitic acid is the principal product of the reaction. Naturally the reaction is enzymatic. Obtained from metazoic and microbial cells. The proposed stoichiometric mechanism is:
7Malonyl-CoA + acetyl-CoA+ 14 TPNH- palmitate+14TPN+ 7CO2 +8CoA2
Wakil and Sterbi et al favored a simple condensation that would yield an alpha-caroxyl-beta-ketothioester, wheras Vagelos and Alberts and Lynenet al have favored a concerted condensation-decarboxylation that would yield a beta-ketothioester.
Using two sources of radiolabelled Carbon can find out which is correct.
Source 1 external from bicarbonate
Source 2 internal from malonyl
As was determined no external bicarbonate source was necessary. The decarboxylation reaction produces CO2.
3. I dreamt about studying fatty acid synthesis in two different experimental systems; cultured rat hepatocytes and Escherichia coli. In my dream I was able to covalently anchor the ketoacyl ACP synthase activities of the fatty acid synthase complexes from both experimental systems to gold nanoparticles (aka quantum dots) through a sulfur-gold bond involving the active site cysteine thiol of -ketoacyl ACP synthase. This resulted in a complete loss of fatty acid synthesis from 14C-1 radiolabelled acetyl CoA in Escherichia coli, but only about 50% reduction in palmitate biosynthesis in the rat liver cells in my dream. Explain the molecular basis for the observations I made in my dream.
While it seems the quantum dots were sufficient in destroying the active site of the enzyme in the E.Coli, there appears to be a second active site from rat heptocytes enzyme not denatured by the quantum dots, but sufficient in halving activity.
4. Niemann-Pick Disease is an inherited disorder of sphingomyelin breakdown due to a deficiency of sphngomyelinase. This enzyme is found in all tissue and