Biomech/chem of bones, joints, and muscles Flashcards
understand the biological basis of bone development and relevance to osteoporosis.
What is the mechanism of action of Nitrogen containing biphosphonates?
Nitrogen-containing biphosphonates such as alendronate, act by reacting with ATP within osteoclasts resulting in apoptosis.
What defines a Gamma carboxygLutamic Acid (Gla) protein domain? How does vitamen K affect the biological activity of the protein.
Gla refers to the carboxylation of glutamatic acid residues within glutamate containing proteins. Vitamin K is a cofactor and necessary for the deveolpment of calcium binding and the protein’s biological activity.
What gene codes for osteocalcin (aka matrix Gla protein, MGP) and how is it expressed?
Osteocalcin is a product of the (Gamma-carboxyGlutamic Acid Protein, Bone) gene (BGLAP) which has 5 glutamic acid residues. Different splice variants develop in different tissues but all require vitamin K for full activity. Cirulating osteocalcin and bone bound osteocalcin have different effects.
What does osteocalcin do and what is the fate of knockout mice ?
Cirulating osteocalcin inhibits vascular calcification, and bone bound calcitonin plays a role in bone organization. Preprosteocalcin mRNA is translated into at lleast 7 variants which are identical at the amino teminus.
Knockout mice without osteocalcin die within two months of arterial calcification with blood vessel rupture.
What is the relationship between osteocalcin and vitamin D ?
Bone content of osteocalcin increases with vitamin D.
How does warfarin induce osteoporosis and arterial calcification?
Warfarin induces osteoporosisi men but not women related to lower intake of vitamin K.
Warfarin induces arterial calcification due to inhibition of gamma carboxylation of matrix Gla protein (MGP). Calcification rate increases markedly with additional vitamin D.
What is the role of vitamin K in metabolism?
Vitamin K is important in modifying coagulation factors, osteocalcin (matrix Gla protein), growth arrest-specific protein 6 (from leukocytes and endothelial cells), transmembrane proteins, and proline-rich Gla-proteins. The functions of the latter 2 are unknown.
What stimuli are helpful in building muscle and what metabolic changes occur ?
Amino acids and exercise plus insulin induce movement of Raptor and mTORC1 to the lysosomal membrane along with RagC and RagA GTPases and Rheb GTPase (Ras Homolog Enriched in Brain) to stimulate protein synthesis by phosporylation of mTOR.
What amino acid is helpful in stimulating muscle growth in the elderly?
Aging skeletal muscle requires higher concentrations of essential amino acids (leucine) and is relatively resistant to insulin and sensitive to decreased blood flow (hypertrophic stimulus), especially following resistance exercise.
How many types of vitamin K are there ?
Vitamen K 1 (Phytomenadione) is synthesized by plants and has an 1,4-napthoquinone base and differs from Vitamin K2 (menaquinone) in the location and length of side chains. Vitamin K2 varies by number of isoprenoid units making up the side chain and the degree of saturation. K2 4 units with one double bond has MK 7 has 7 isoprenoid units with 7 double bonds.
What type of vitamin K affects osteocalcin ?
The osteocalcin effect requires higher doses of vitamin K than the coagulation effect. Vitamin K2 and MK 7 can increase active osteocalcin but not vitamin K1. K2 can increase bone density, but not in postmenopausal women even though osteoporosis is associated with arterial calcification.
