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31 Cards in this Set
- Front
- Back
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What is the definition of Vitamin K?
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It is a CLASS of compounds derived from napthoquinone (aka menadione) & which have antihemorrhagic activity
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What are the vitamer forms and what is the difference in their structures?
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1. Menadione - two ring structure w/ no side chain
2. phylloquinone (plants) - side chain w/ no double bonds "phytal" side chain 3. Menaquinone (bacteria) - side chain w/double bonds - isoprene units |
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Which forms are active?
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The side chain must be present - menadione converted to menaquinone in liver. Then, Vit K --> KH2 for activation
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What is the biochemical function of Vitamin K?
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Vitamin K is a participant in the posttranslational carboxylation of glutamate (glu) to gamma-carboxyglutamate (gla)
COOH group attaches to g-carbon of glutamate. |
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In what classes of proteins are these reactions important? Give specific protein examples for each.
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Blood Clotting Proteins - eg prothrombin and Christmas factor
Bone Matrix Proteins - eg osteocalcin |
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Why are gla residues important for blood clotting?
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Gla residues can bind with Ca2+ causing conformational change in the protein and enabling enzymes
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Describe the blood clotting mechanism and discuss how Vit K fits in
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The coagulation of blood is a series of membrane-localized, cascading reactions involving modification of proteins: some of which depend on the presence of Vit K.
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What is osteocalcin important for?
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Bone building. Lack of vit K can result in osterperosis.
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What is the Vitamin K cycle?
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The cycle of activation and regeneration of Vit K.
K-->KH2-->K epoxide & back |
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What are the rxns/enzymes involved in the Vitamin K cycle?
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K + NADPH+H--> KH2 + NADP
enzyme: Vitamin K reductase KH2 --> Vit K epoxide enzyme: Vit K Carboxylase **This step Glu-->Gla! K epoxide --> K enzyme: Vit K epoxide reductase |
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KH2 is also refered to as?
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Vit K hydroquinone
aka "reduced" Vitamin K |
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Where do the H's go in K-->KH2?
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The form we eat, Vit K, is in th fully oxidizied =O's
H's attached to =O --> -OH groups |
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What inhibits the Vitamin K cycle? And where in the cycle?
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Coumarins including warfarin and dicumarol. They are classified as anti-coagulants. Glu cannot become Gla as readily and so it inhibits blood clotting.
Specifically: epoxide reductase is inhibited |
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What is "special" about the carboxylase enzyme?
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It is membrane bound.
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What is the first step for carboxylation reactions?
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The Vit K dependent protein and Vitamin K must "bind" with the carboxylase enzyme. Three binding sites: Pro-peptide binding side, Glu binding site, and Vit KH2 binding site.
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After the substrates (Vit KH2 and the protein) have bound to the carboxylase enzyme, what occurs next?
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Vitamin K is deprotonated by
----cys----- | S group on enzyme (weak base) (the OH nearest the side chain is the one) |
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After deprotonation of KH2, what then?
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KH reacts with oxygen to form dioxetane which is rearranged into the epoxide/ a hydroxyl group (OH-) is release. STRONG BASE!!!
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So we have a strong base formed; now what?
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This strong base is able to deprotonate Glu, forming water & Glu-carbanion.
Deprotonated glu is attracted to CO2 (held in place by SECOND Cys-SH group). Gets CO2. Gla formed. |
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What is meant by "base amplification"?
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A relatively weak base, -S is used to form a very strong base, -OH which leads to the deprotonation of Glu.
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What are some vit K deficiency signs?
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Hemorrhaging.
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Who are most susceptible?
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Elderly AND breast-fed Newborns
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What is the deficiency disease in babies called?
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Hemorrhagic Disease of the Newbown (HDN)
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Why are newborns susceptible?
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Low status; mother's milk low in Vit K
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When does HDN occur, symptoms? Treatment?
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HDN: 2 to 6 days after bith
intracrannial hemmorhage, GI bleeding Treat with injections of menadione! |
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How is Vit K assessed?
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Serum phylloquinone most common
Can also use "Protime" |
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What is "Protime"?
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Prothrombin time. In vitro method of measuring time to clot.
Insensitive for assesment of status, but good for monitoring anti-coagulation therapy. |
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Food sources?
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Leafy greens, liver
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What are some examples of blood clotting proteins dependent on Vit K for modification?
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Prothrombin and Christmas factor
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What is an example of a bone matrix protein dependent on Vit K for modification?
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Osteocalcin: most abundant non-collagen protein in bone matrix.
synthesized by osteoblasts; binds to hydroxyapatite; assoc. w/new bone formation. |
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Vitamin KH2 is called what?
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Vitamin K hydroquinone.
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Before the Vit K epoxide is formed by rearrangement, what is the form called (linked to the O2)?
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Dioxetane
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