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1. What are the 3 forms of Vitamin K? What is the most common form and the only form that can be made in mammalian tissues? What is it made from?
2. What is bioavailability in cooked spinach? What happens when you add fat? Why is bioavailability the way it is? How is free vitamer absorbed?
3. Which types of vitamers of vitamin K are poorly absorbed and less active?
1. K1 (phylloquinone) K2 (menaquinone) synthetic (menadione). MK-4 (common & made in mammalian tissues from vitamin K1)
2. 5%, 13%, bc Vitamin K is trapped. Free vitamer bioavailability is ~80%
3. Longer chains
How can menaquinones be modified?
Can add 3-9 different groups (short or long chain)
What are the functions of Vitamin K?
1. Blood clotting cascade - important for both pro and anti-clotting proteins
1. What is the more common clotting pathway?
2. Thru what mechansim does Vitamin K work?
3. Where are vitamin K dependent proteins synthesized? How many? What amino acid do they contain? What form are these AAs in? What are they converted to? What ion is needed?
- 1. Extrinsic
- 2. Redox
- 3. Liver, 7, Gla (zymogen) --> Serine. Need calcium.
1. Why don't we need high intakes of vitamin K?
2. What is the role of vitamin K specifically? What form? Name of form? What is the substrate? What is final product?
3. Where does Ca2+ come in?
- 1. Vitamin K is efficiently recycled
- 2. Reduced vitamin K (hydroquinone) is needed to modify glutamate residue into gamma-carboxylated glutamate. (Glu --> Gla)
- 3. Vitamin K is needed to modify Glu into gamma-carboxylated glutamate so that these proteins can form Ca2+ bridges between (1) clotting factors and phospholipids on membrane surfaces of blood platelets and endothelial/vascular cells (2) Gla residues to form internal Gla-Gla linkages.
Draw cycle of Glutamate to Gla and how Vitamin K is regenerated
Draw 3 enzymes and 3 forms of Vitamin K
Where does vitamin K regeneration generally occur?
In which enzyme is there genetic variability? What does this lead to?
For clotting cascade, mostly happens in the liver.
Vitamin K epoxide reductase - leads to variability in patient response to anti-coagulant therapy
1. What does human gut contain?
2. How do we know that bacterially produced vitamin K2 is absorbed by body?
3. Can animals synthesize?
4. Is breast milk a good source of vitamin K?
- 1. K2 menaquinones produced by bacteria
- 2. Because liver contains significanta mounts
- 3. No, but can get from bacteria in gut or dark leafy greens, etc
- 4. No
Where is vitamin K absorbed? What does it depend on? (3)
What affects absorption rates?
How is Vitamin K absorbed? (2) - where? Basically, what do we need to know?
- 1. In all areas of small intestine
- 2. Depends on bile, micelles, pancreatic lipases like all other fat-soluble vitamisn
- 3. Content of micelles
- 4. K1 (active) - occurs in proximal small intestine, no other competition.
K2 (passive, non-carrier mediated) occurs in distal small intestine & colon.
Just know K1 = active and K2 = passive
How is Vitamin K transported into blood? Where does it go? What are plasma carriers for Vitamin K?
Where are the different forms of Vitamin K taken up by? How much is stored? What is rate of metabolism and secretion? What is it excreted in? (2)
Chylomicrons to liver. NO PLASMA CARRIERS, probably just uses VLDL and LDL
K1 and K2 are taken up by liver while menaquinone is taken up by wide variety of tissues. Very little is stored in hepatocytes. Very rapid metabolism and secretion.
Excreted in urine and feces.
What is the difference between hemophilia and vitamin K deficiency?
What are the two types and which is most common?
In hemophilia, there is an ENZYME deficiency, not vitamin K deficiency. IMPORTANT TO DIFFERENTIATE!
Haemophilia A (most common) Hemophilia B
What is the predominant clinical sign of Vitamin K def? Who is this most often seen in?
What can result from Vitamin K def? (2)
Is Vitamin K def common in humans? Why or why not?
What are 4 risk factors?
- 1. Hemorrhage, most often seen in newbrons
- 2. Reduced bone density and increased risk of fractures
No, bc amount synthesized by gut bacteria is enough.
Lipid malabsorption, alcoholism, anticoagulation therapy, and neonates
Why are neonates frequently at risk? (4)
What are they given at birth?
1. Because transplancental transport of vitamin K is poor, newborns have sterile guts for first few days (no biosynthesis), and hepatic biosynthesis of clotting factors is inadequate Human milk isn't good source either.
Vitamin K shot
What is an example of a famous antagonist? Who needs antagonists? (3)
- 1. Warfarin
- 2. Artificial heart valves, deep venous thrombosis (DVT) and pulmonary embolism
What is Vitamin K's role in bones? - 3 proteins. What happens if you have a def of the last one in children?
There are 3 vitamin K dependent proteins in bone: osteocalcin (made by osteoblasts) MGP (matrix protein) and protein S
MGP assists with bone matrix calcification and protects soft tissue from artery calcification
Protein S is synthesized by osteoblasts, needed for strong bones. Children with protein S deficiency often have osteopenia
What are case studies we looked at? 2
- 1. Short bowel syndrome leading to easily bruising
- 2. Pulmonary embolism when someone is on birth control and inactivity