Dr.Avinash Jadhao 10/6/20181

2 Vitamin K- Chemistry Vitamin K represents a group of lipophilic and hydrophobic vitamins. Three compounds have the biological activity of vitamin K Phylloquinone (Vitamin K1), the normal dietary source, found in green vegetables Menaquinones (vitamin K2), synthesized by intestinal bacteria, with differing lengths of side chain; Menadione Vitamin K3 and menadiol diacetate, synthetic compounds that can be metabolized to phylloquinone.

Vitamin K- Chemistry 10/6/20183

4 Vitamin K- Chemistry Vitamin K family are naphthoquinone derivatives Phylloquinone and menaquinones, both have a long isoprenoid side chain. The length of the side chain differs. Phylloquinone 20 C side chain Menaquinones 30 C side chain. The synthetic vitamin K (menadione, menadiol diacetate) have only hydrogen in place of isoprenoid side chain that makes these vitamin water-soluble. Vitamin K family are naphthoquinone derivatives Phylloquinone and menaquinones, both have a long isoprenoid side chain. The length of the side chain differs. Phylloquinone 20 C side chain Menaquinones 30 C side chain. The synthetic vitamin K (menadione, menadiol diacetate) have only hydrogen in place of isoprenoid side chain that makes these vitamin water-soluble.

Vitamin K is found in green leafy vegetables such as kale and spinach, and Appreciable amounts are also present in margarine and liver. Vitamin K is present in vegetable oils and is particularly rich in olive, canola, and soybean oils. Some amount is contributed by intestinal bacteria Vitamin K is found in green leafy vegetables such as kale and spinach, and Appreciable amounts are also present in margarine and liver. Vitamin K is present in vegetable oils and is particularly rich in olive, canola, and soybean oils. Some amount is contributed by intestinal bacteria 10/6/20185 Dietary Sources

10/6/20186

Absorption, Transportation and Storage Absorption takes place in intestine in the presence of bile salts. The transportation from intestine is carried out through chylomicrons. Storage occurs in liver and from liver transportation to peripheral cells is carried out bound with beta lipoproteins. Absorption takes place in intestine in the presence of bile salts. The transportation from intestine is carried out through chylomicrons. Storage occurs in liver and from liver transportation to peripheral cells is carried out bound with beta lipoproteins. 10/6/20187

Impaired absorption of vitamin K Fat malabsorption is associated with impaired absorption of vitamin K and other fat soluble vitamins. Vitamin K is important for the coagulation process. In its deficiency coagulation process is grossly affected resulting in tendency for bleeding and hemorrhages. Absorption of vitamin K may also be decreased by mineral oil, bile acid sequestrants (Cholestyramine, Colestipol) and Orlistat (weight loss medication). Fat malabsorption is associated with impaired absorption of vitamin K and other fat soluble vitamins. Vitamin K is important for the coagulation process. In its deficiency coagulation process is grossly affected resulting in tendency for bleeding and hemorrhages. Absorption of vitamin K may also be decreased by mineral oil, bile acid sequestrants (Cholestyramine, Colestipol) and Orlistat (weight loss medication). 10/6/20188

9 Impaired absorption of vitamin K

70 µ g-140 /day

Recommended daily allowance Requirement increases in – Liver disorders Patients on prolonged antibiotic therapy, bile acid sequestrants (Cholestyramine, colestipol) and Orlistat (weight loss medication) Requirement increases in – Liver disorders Patients on prolonged antibiotic therapy, bile acid sequestrants (Cholestyramine, colestipol) and Orlistat (weight loss medication) 10/6/201811

Functions of vitamin K Vitamin K is essential for normal coagulation of blood Concentrations of several coagulation factors in plasma are decreased in vitamin K deficiency These include prothrombin (Factor II), proconvertin (Factor VII), Christmas factor (Factor IX) and Stuart-Prower Factor (Factor X) Vitamin K is essential for normal coagulation of blood Concentrations of several coagulation factors in plasma are decreased in vitamin K deficiency These include prothrombin (Factor II), proconvertin (Factor VII), Christmas factor (Factor IX) and Stuart-Prower Factor (Factor X) 10/6/201812

10/6/ All these factors are proteins, and vitamin K is required for post-translational modification of these proteins, which is necessary for their Activation Prothrombin is synthesised in liver in the form of an inactive precursor, pre-prothrombin

10/6/ Vitamin K-dependent gammacarboxylation

10/6/201815

10/6/ Calcium binding proteins Vitamin K–dependent proteins are a heterogeneous group, including = clotting factor proteins and proteins found in bone lung kidney, and placenta. Functions of vitamin K

Vitamin K cycle Reduced lipoamide is required for the activity of Epoxide reductase whereas NADPH is needed for the action of vitamin K reductase. 10/6/201817

10/6/2018 Biochemistry for medics- Lecture Notes- Namrata Chhabra18 Deficiency Deficiency of vitamin K leads to a disturbance in the normal mechanism of coagulation of blood Even a slight injury causes prolonged bleeding in a subject deficient in vitamin K Diagnosis can be made by measuring prothrombin time which is prolonged in vitamin K deficiency.

10/6/2018 Biochemistry for medics- Lecture Notes- Namrata Chhabra19 Prothrombin time may also be prolonged in patients with liver damage due to inability of the liver to synthesise prothrombin These two conditions can be distinguished by parenteral administration of vitamin K Prothrombin time returns to normal in subjects deficient in vitamin K but not in patients with liver damage

A deficiency of vitamin K can lead to extreme bleeding, which can begin as a gum or nose discharge or bruising 10/6/ Clinical Manifestations

Laboratory Studies A prolonged PT is usually the first laboratory test result to be abnormal in vitamin K deficiency bleeding due to reduction in Prothrombin F II FVII, FIX FX levels. A prolonged PT is usually the first laboratory test result to be abnormal in vitamin K deficiency bleeding due to reduction in Prothrombin F II FVII, FIX FX levels. 10/6/201821

Treatment Patients with liver disease may have an elevated prothrombin time because of liver cell destruction as well as vitamin K deficiency. If an elevated prothrombin time does not improve on vitamin K therapy, it can be deduced that it is not the result of vitamin K deficiency. Patients with liver disease may have an elevated prothrombin time because of liver cell destruction as well as vitamin K deficiency. If an elevated prothrombin time does not improve on vitamin K therapy, it can be deduced that it is not the result of vitamin K deficiency. 10/6/201822

10/6/ People who have vitamin K deficiency and a severe liver disorder may also need blood transfusions to replenish the clotting factors. A damaged liver may be unable to synthesize clotting factors even after vitamin K injections are given. The reversal of excessive anticoagulant therapy with Warfarin or Warfarin-like drugs can be achieved by minimal doses of vitamin K (1 mg orally or by intravenous injection) for asymptomatic patients. People who have vitamin K deficiency and a severe liver disorder may also need blood transfusions to replenish the clotting factors. A damaged liver may be unable to synthesize clotting factors even after vitamin K injections are given. The reversal of excessive anticoagulant therapy with Warfarin or Warfarin-like drugs can be achieved by minimal doses of vitamin K (1 mg orally or by intravenous injection) for asymptomatic patients. TreatmentTreatment

Toxicity Toxicity from dietary phylloquinone and menaquinones has not been described. High doses of vitamin K can impair the actions of oral anticoagulants. 10/6/201824

10/6/ Intramuscular (IM) vitamin K prophylaxis at birth is the standard of care. Commercial infant formulas contain supplemental vitamin K. These measures have served to make vitamin K deficiency bleeding a rarity. However, parental refusal of prophylaxis and an increasing frequency of breastfeeding may cause a resurgence of vitamin K deficiency bleeding in developed countries. PreventionPrevention