Biochemistry MSK Flashcards
What are the different subsets of collagen?
Fibril-forming
Network-forming
Fibril-associated
Explain the structure of the fibrous protein of collagen.
3 a-chains forming a triple stranded rope.
Each chain has 1000 AA
The chain is stabilized by intracranial H-bonds
Each third amino acid is Glycine.
What is the genetic difference of collagen type 1 and 2
Type one is 2 stands coded by a1 genes and 1 strand of a2.
Type two is 3 strands of a1 genes.
Which modified amino acid allows for hydrogen bonding between alpha chains?
Hydroxyproline
Has the OH group.
What things do post-translational hydroxylation require, and what is one disease that can be acquired without one of these things?
O2, Fe2+, Ascorbate (Vitamin C)
Scurvy: less tensile strength of collagen due to lack of H-bond formation.
Which enzyme aids in cross linking of collagen fibers, and what ion does it contain?
Explain that process, and which disorder goes along with genetic problems of crosslinking.
Lysol oxidase, and it has copper to aid in extracellular crosslinking.
Assembly of the triple helix in ER
N and C end proteinases that helped the helix structure are cut off.
Lysol oxidase cavalently links collagen fibrils outside of the cell.
X-linked recessive gene: Menkes Syndrome (kinky hair). Mutations that lead to lack of Cu2+.
Name and describe 2 collagenopathies
Osteogenesis Imperfecta (brittle bone syndrome). Mutations in collagen 1 by replacement of Gly.
Symptoms: blue sclerae, brittle bones
Ehlers-Danlos Syndrome: Defective collagens or processing enzymes. Involve collagen 5 in classic form and 3 in vascular form.
Symptoms: hyperextensible skin, abnormal tissue fragility. Most severe is potentially lethal vascular problems due to defective collagen in the arteries.
Explain the make up of Elastic Fibers.
Lysyl oxidase modifies lysyl side chain to form desmosine.
Fibrillin acts as the scaffold for elastin
Desmosine and Fibrillin
Explain 2 elastic fiber Genetic Disorders
Marian Syndrome
Mutations in Fibrillin 1 protein
Autosomal dominant: pleiotropic
Symtpoms: Arachnodactyly (long fingers, positive wrist sign), ectopic lensis, weak large arteries.
Williams-(Beuren) syndrome
Chromosomal #7 deletion of 27 genes including elastin.
Random event during formation of reproductive cells. Inherited in small % of cases.
Presentation: developmental disorder, unique personality, distinctive facial features, cardiovascular problem.
Explain the 2 kinds of Adhesion Proteins. And one related disorder
Laminin: large cross-shaped quartnary protein. Holds component of basement membrane
Fibronectin: Most abundant multi-adhesive protein.
Function: Gives cells the fibrous mesh work of the ECM. Quartnary
LAMA2-related muscular dystrophy
Mutation in the LAMA2 gene, messes with laminin 2 and 4 production.
Autosomal recessive.
Presentation: Muscle weakness. Can be early onset or milder late onset.
Explain the difference between Proteoglycans vs Glycoproteins
Proteoglycans: Carbs w/ little protein
Glycoproteins: Protein w/ little carbs.
Explain the 3 structures of the Aggregate
Proteoglycans monomer: - Glycosaminoglycans (GAG) - Core Protein Hyaluronic acid (type of GAG) Link Protein
What are GAGs charge?
Negative
Acidic sugar is negative, amino sugar is +, but it is eliminated and changed to -.
What are the names of the 6 kinds of GAGs, explain them.
Chondroitin 4- and 6-Sulfates:
Most abundant, found in cartilage, tendons, ligaments, and aorta. Form Proteoglycans aggregates
Keratin Sulfates (KS) 1 and 2: Most heterogeneous GAG. Found in corneas, loose connective tissue Proteoglycans aggregates
Hyaluronic Acid:
Not sulfates or covalently attached to protein like other GAG. Also found in bacteria.
Serves as lubricant and shock absorber in synovial fluid, vitreous humor, loose CT, and cartilage
Dermatan Sulfate:
Found in skin, blood vessels, and heart valves
Heparin:
A-linkage joins the sugars, intracellular (only GAG) component of mast cells that line arteries in liver, lungs, and skin. Anticoagulant.
Heparin Sulfate:
Extracellular GAG found in basement membrane and as a ubiquitous component of cell surfaces.k
What are the two problems that can go wrong with GAG and what are their associated diseases?
Synthesis and Degradation
Synthesis: Chondrodystrophies: defect in the Sulfate one of the growing GAG chain.
Autosomal recessive: Dwarfism
Degradation: Mucopolysaccharidoses: deficiency of any one of the lysosomal hydrolases involved in the degradation of heparin sulfate and/or dermatan sulfate Autosomal Recessive (except Hunter syndrome, X linked) Progressive disorders that appear normal at birth. GAG accumulate in lysosomes, urine, and various tissues, skeletal and ECM deformities with mental retardation
Types:
Hurler Syndrome: Most severe
Sanfilippo Syndrome: Severe nervous system disorders. 4 enzymatic steps for N-Sulfate residues.
Hunter Syndrome: X-linked: enzyme replacement therapy, degradation of dermatan sulfate and heparin sulfate affected.
SLY syndrome: B-Glucuronidase deficiency. Short stature, corneal clouding, developmental disability.
Which GLUT transporter is insulin dependent and in muscles?
GLUT 4
Facilitated Diffusion: ATP Independent
When insulin is in blood more GLUT 4 is transferred in vessicles to PM to bring glucose in.
Type 2 diabetes and Insulin resistance
What enzyme activates glucose inside muscle cells?
Hexokinase
3 isoforms
Inhibited by it own end product G6P.
High affinity for glucose (low Km) with low Vmax
Explain the first rate-limiting step of glycolysis
Phosphofructokinase-1 (PFK-1)
Irreversible, and first rate-limiting and committed step.
Inhibited by: ATP and citrate
Activated in muscle by: AMP
Activated in liver by: F-2,6-bisP
