CHAPTER 47: VITAMIN K
OBJECTIVES
Identify dietary and structural differences between the phylloquinones and menaquinone, and discuss differences in hepatic forms of vitamin K between dogs and horses.
Phylloquinones and menaquinone are two types of vitamin K. Phylloquinones are found in green leafy vegetables and are the primary dietary source of vitamin K1. Menaquinone is produced by bacteria in the gut and is the primary dietary source of vitamin K21.
The differences between phylloquinones and menaquinone are in their side chains. Phylloquinone has a side chain of four isoprenoid residues, three of which are saturated. Menaquinone has several forms, each with an isoprenoid side chain, designated MK-4 (or menatetrenone) through MK-13 according to the length of the side chain2.
Dogs and horses have different hepatic forms of vitamin K. Dogs have a higher concentration of vitamin K1 in their liver than horses do. Horses have a higher concentration of vitamin K2 in their liver than dogs do.
Describe how most ruminants, horses, rodents, rabbits, dogs and cats satisfy their vitamin K requirements.
Through the synthesis or Vitamin K by the bacteria in their gut.
Explain why orally administered K3 may appear at higher concentrations in the hepatic portal circulation than orally administered K1 or K2.
Vitamin K3 is water-soluble and can be absorbed in the absence of bile acids, passing directly from intestinal mucosal cells into the hepatic portal circulation. The liver is the main repository of these vitamins, although there appears to be a rapid turnover; consequently, body pools are thought to be small
Recognize why the liver can continue its production of clotting factors in vitamin K deficiency, yet those factors remain dysfunctional.
The liver can continue its production of clotting factors in vitamin K deficiency because vitamin K is required for the activation of clotting factors II, VII, IX and X. In vitamin K deficiency, these factors remain dysfunctional because they are not fully activated
Indicate how hepatic Á-carboxyglutamate is formed, where it is found, and how it functions.
Hepatic Á-carboxyglutamate is formed by the carboxylation of glutamic acid residues in vitamin K-dependent proteins. This process is catalyzed by the enzyme gamma-glutamyl carboxylase.
Á-carboxyglutamate is found in vitamin K-dependent proteins such as coagulation factors II, VII, IX and X and anticoagulant proteins C and S.
Á-carboxyglutamate functions by binding calcium ions and allowing these proteins to interact with negatively charged phospholipids on cell membranes. This interaction is necessary for the activation of coagulation factors and the inhibition of anticoagulant proteins.
Discuss relationships that exist between bone Gla protein, 1,25(OH)2D, PTH and Ca++ homeostasis.
Bone Gla protein (BGP) is a vitamin K-dependent protein that is synthesized by osteoblasts in bone. BGP is also known as osteocalcin.
1,25(OH)2D stimulates the synthesis of BGP in osteoblasts1.
Parathyroid hormone (PTH) stimulates the release of calcium from bone by increasing the activity of osteoclasts. PTH also stimulates the synthesis of 1,25(OH)2D in the kidneys1.
Calcium homeostasis is regulated by PTH and 1,25(OH)2D. PTH increases calcium levels in the blood by stimulating the release of calcium from bone and increasing calcium reabsorption in the kidneys. 1,25(OH)2D increases calcium levels in the blood by increasing calcium absorption in the intestines
Understand why vitamin K is sometimes used as a therapeutic antidote to sweet clover and rat poisoning.
Vitamin K is sometimes used as a therapeutic antidote to sweet clover and rat poisoning because these poisons contain coumarin derivatives that inhibit vitamin K-dependent carboxylation of coagulation factors II, VII, IX and X. Vitamin K can reverse the anticoagulant effects of these poisons by providing an alternative source of vitamin K
Explain why vitamin K deficiency can present itself before other fat-soluble vitamin deficiencies, and identify vitamin K deficiency symptoms.
Vitamin K deficiency can present itself before other fat-soluble vitamin deficiencies because vitamin K is not stored in the body to the same extent as other fat-soluble vitamins. Vitamin K deficiency symptoms include easy bruising, bleeding gums, nosebleeds, and blood in the urine or stool
OBJECTIVES
Identify dietary and structural differences between the phylloquinones and menaquinone, and discuss differences in hepatic forms of vitamin K between dogs and horses.
Phylloquinones and menaquinone are two types of vitamin K. Phylloquinones are found in green leafy vegetables and are the primary dietary source of vitamin K1. Menaquinone is produced by bacteria in the gut and is the primary dietary source of vitamin K21.
The differences between phylloquinones and menaquinone are in their side chains. Phylloquinone has a side chain of four isoprenoid residues, three of which are saturated. Menaquinone has several forms, each with an isoprenoid side chain, designated MK-4 (or menatetrenone) through MK-13 according to the length of the side chain2.
Dogs and horses have different hepatic forms of vitamin K. Dogs have a higher concentration of vitamin K1 in their liver than horses do. Horses have a higher concentration of vitamin K2 in their liver than dogs do.
Describe how most ruminants, horses, rodents, rabbits, dogs and cats satisfy their vitamin K requirements.
Through the synthesis or Vitamin K by the bacteria in their gut.
Explain why orally administered K3 may appear at higher concentrations in the hepatic portal circulation than orally administered K1 or K2.
Vitamin K3 is water-soluble and can be absorbed in the absence of bile acids, passing directly from intestinal mucosal cells into the hepatic portal circulation. The liver is the main repository of these vitamins, although there appears to be a rapid turnover; consequently, body pools are thought to be small
Recognize why the liver can continue its production of clotting factors in vitamin K deficiency, yet those factors remain dysfunctional.
The liver can continue its production of clotting factors in vitamin K deficiency because vitamin K is required for the activation of clotting factors II, VII, IX and X. In vitamin K deficiency, these factors remain dysfunctional because they are not fully activated
Indicate how hepatic Á-carboxyglutamate is formed, where it is found, and how it functions.
Hepatic Á-carboxyglutamate is formed by the carboxylation of glutamic acid residues in vitamin K-dependent proteins. This process is catalyzed by the enzyme gamma-glutamyl carboxylase.
Á-carboxyglutamate is found in vitamin K-dependent proteins such as coagulation factors II, VII, IX and X and anticoagulant proteins C and S.
Á-carboxyglutamate functions by binding calcium ions and allowing these proteins to interact with negatively charged phospholipids on cell membranes. This interaction is necessary for the activation of coagulation factors and the inhibition of anticoagulant proteins.
Discuss relationships that exist between bone Gla protein, 1,25(OH)2D, PTH and Ca++ homeostasis.
Bone Gla protein (BGP) is a vitamin K-dependent protein that is synthesized by osteoblasts in bone. BGP is also known as osteocalcin.
1,25(OH)2D stimulates the synthesis of BGP in osteoblasts1.
Parathyroid hormone (PTH) stimulates the release of calcium from bone by increasing the activity of osteoclasts. PTH also stimulates the synthesis of 1,25(OH)2D in the kidneys1.
Calcium homeostasis is regulated by PTH and 1,25(OH)2D. PTH increases calcium levels in the blood by stimulating the release of calcium from bone and increasing calcium reabsorption in the kidneys. 1,25(OH)2D increases calcium levels in the blood by increasing calcium absorption in the intestines
Understand why vitamin K is sometimes used as a therapeutic antidote to sweet clover and rat poisoning.
Vitamin K is sometimes used as a therapeutic antidote to sweet clover and rat poisoning because these poisons contain coumarin derivatives that inhibit vitamin K-dependent carboxylation of coagulation factors II, VII, IX and X. Vitamin K can reverse the anticoagulant effects of these poisons by providing an alternative source of vitamin K
Explain why vitamin K deficiency can present itself before other fat-soluble vitamin deficiencies, and identify vitamin K deficiency symptoms.
Vitamin K deficiency can present itself before other fat-soluble vitamin deficiencies because vitamin K is not stored in the body to the same extent as other fat-soluble vitamins. Vitamin K deficiency symptoms include easy bruising, bleeding gums, nosebleeds, and blood in the urine or stool
