Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Enzymatic Hydrolysis and Group Transfer Reactions 117
(3) Cysteine proteases are eVectively inhibited by substrate analogues containing
an aldehyde functional group in place of the amide targetted by the
enzyme. Suggest a possible mechanism of inactivation.
(4) Acetyl CoA is biosynthesised from acetate by diVerent pathways in bacteria
versus higher organisms, as shown below. In the case of the bacterial
pathway incubation of 18 O-labelled acetate yields one atom of 18 O in the
phosphate product, whereas in higher organisms the same experiment
yields one atom of 18 O in the adenosine monophosphate (AMP) product.
Suggest intermediates and mechanisms for the two pathways.
Bacteria:
CH 3 CO −
2 + ATP + CoASH
(1) acetate kinase
(2) phosphotransacetylase
CH 3 COSCoA + ADP + P i
Higher organisms:
CH 3 CO −
2 + ATP + CoASH
acetate thiokinase
CH 3 COSCoA + AMP + PP i
(5) Glycogen is a mammalian polysaccharide consisting of repeating
a-1,4-linked d-glucose units. It is stored in liver and muscle and is used as
a carbohydrate energy source by the body, being converted to d-glucose
when required by the pathway shown below. Suggest mechanisms for each
of the enzymes on the pathway. What would be the medical consequences
of a genetic defect in muscle glycogen phosphorylase
OH
O
HO
O
OH
O
HO
glycogen
OH
O
OH
O
n
glycogen
phosphorylase
Na 2 HPO 4
HO
HO
OH
O
OH
OPO 2−
3
phosphoglucose
isomerase
D-glucose
HO
HO
OH
O
glucose
6-phosphatase
HO
HO
OPO 2−
3
O
OH
OH
P i
OH
OH