In the absence of the vitamin, the blood-clotting time increases, since the post-translational
carboxylation of several glutamate residues in prothrombin and other factors involved in
blood clotting is impaired. In humans, this disorder is unknown except in cases of faulty
vitamin K absorption, since the normal diet covers the need generously.
Vitamin K antagonists, such as dicoumarol (8.61, a natural product) and warfarin
(8.62), are used as anticoagulants in human therapy (thrombosis, atherosclerosis) and
as rat poisons that lead to internal bleeding and death in rodents. Heparin,a polysac-
charide consisting of 2-0-sulfonated glucuronic acid and 2-N,6-0-disulfonated glu-
cosamine, is also a widely used anticoagulant, but its effect is connected not with
Vitamin K but with enzyme inhibition.
8.2.9 Molecular–Clinical Interface: Human
Disease and Enzyme Cofactors8.2.9.1 Case Studies
In a single 12 hour period, one of the authors saw the following five sequential patients
in the emergency department of an urban teaching hospital.
Patient 1. This 32-year-old markedly obese female had undergone a gastric stapling
operation to decrease the size of her stomach and thus promote weight loss. Although
she had recovered well from the surgical procedure, in the ensuing 3–4 weeks she had
only been able to take fluids, vomiting all solid foods. Nevertheless, since she was
rapidly losing weight, she did not complain. Suddenly, over the course of 24 hours, she
rapidly developed confusion (not recognizing her children or spouse), ataxia (staggering
gait when walking and inability to stand), and diplopia (double vision). A diagnosis of
Wernicke’s syndromesecondary to acute thiamine deficiency was made. Following the
administration of 50 mg of thiamine intravenously, her confusion and diplopia resolved
within hours.
512 MEDICINAL CHEMISTRY