Week 1 Flashcards
Collagen Biosynthesis Disorder Type 1 Diseases?
Osteogenesis Imperfecta and Ehlers-Danlos
What can Osteogenesis Imperfecta lead to?
Dentinogenesis Imperfecta Type 1
Discolored and broken down enamel and structure.
Collagen Biosynthesis Disorder Type II Diseases?
Skeletal Displasia, vitreous abnormalities, hearing impairment
Osteogenesis Imperfecta symptoms?
Curved long bones that are weak leading to deformed body
What type of collagen is needed to endochondral/long bone ossification and what results in the body?
Type II- Short bones/dwarfism, underdeveloped jaw, cleft palates, Pierre robin sequence, stickler syndrome, retina detachment and blindness
Collagen Biosynthesis Disorder Type III Diseases?
Keloid formation and Elher Danlos type IV
Collagen Biosynthesis Disorder Type IV Diseases?
Goodpasture Syndrome aka producing antibodies against collagen in lungs and kidneys
Alport Syndrome
Loss of kidney function and hearing
Epidermolysis Bullosa- fragile and blistering skin
Tissue that collagen type I is found in?
Bone skin and tendons
Tissues that collagen type II is found in?
Cartilage and vitreous humor
Tissues that collagen type III is found in?
Blood vessels and granulation tissue
Tissues that collagen type IV is found in?
Basement membranes
How does Vit C affect collagen?
Needed for the for the hydroxylation of procollagen side chains. Deficiency of vit c results in insufficient hydroxyproline and no cross linking of of collagen fibrils = scurvy
Symptoms of scurvy?
Gingival swelling, rash/mucocutaneous petechiae, poor wound healing, peri follicular papules, edema of lower limbs
Bleeding into joint cavities/hemarthrosis
Brittle bones
Elastin?
Connective tissue in lungs skin ligaments and arteries
No hydroxylysine making it more elastic
What is alpha antitrypsin?
It inhibits elastase that breaks down elastin
When elastin is broken down lungs are less elastic/emphysema
What are plasma proteins?
Made in liver and balance pH
More later
What is hemoglobin?
In red blood cells only Carries oxygen 4 hemes Hb binds CO2 in blood Sickle cell anemia is mutation in it
Myoglobin details
In heart and skeletal muscles
1 heme
Stores O2
Carrier of O2
Pneumonic to memorize essential amino acids?
PVT TIM HALL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine (only during growth/positive nitrogen balance)
Leucine
Lysine
5 physiologically relevant proteins?
Collagen, elastin, plasma proteins, hemoglobin, myoglobin
What are inhibitors of prokaryotic protein synthesis?
Streptomycin Erythromycin Clindamycin Tetracycline Chloramphenicol
What are inhibitors of eukaryote protein synthesis
Cycloheximide
Diphtheria toxin
Pseudomonas toxin
What happens when a baby if given to much chloramphenicol?
Grey baby syndrome
They don’t have an enzyme to metabolize excess
Blue lips and ashen grey skin
Xeroderma pigmentosum
Defective nucleotide excision repair
Can’t fix DNA damage from sun
Burns tumors photophobia in eyes with pink eye
What is a disease caused from a defect in mismatch repair?
Lynch syndrome
Colorectal cancer endometrial cancer
Does RNA polymerase proofread?
No!
Holoenzyme
Whole enzyme complex with cofactors
Catalytic site?
Where the enzyme bonds to protein to go through a conformational change to lower activation energy of protein
Coenzyme?
Non protein cofactor of vitamins
Cofactors?
Non proteins metal ions need to activate the enzyme
What factors affect kinetic properties of enzymes?
Substrate concentration
Temp
Enzyme concentration
pH
First 3 if increased increase reaction rate
Km and how to recognize it on MM equation plot?
Km= affinity of an enzyme for its substrate
Higher number = less affinity
Km is 1/2 of Vmax on MM chart
What is the Lineweaver Burke plot?
Reciprocal form of MM equation plot. Easier to spot a Vmax where line crosses y axis
Allosteric enzyme?
Enzymes with a separate binding site for an effector which when binds causes the active site to either open or close
either a repressor or activator
Does an allosteric enzyme change Vmax and Km?
Yes they don’t follow MM equation
3 types of enzyme inhibition?
Competitive
Uncompetitive
Non competitive
Competitive inhibitors?
Bind at substrate site
Reversed by increasing substrate
Uncompetitive?
Binds at different site but
ONLY to ES complexity
Can’t be reversed by increasing substrate
Noncompetitive?
Binds at different site to enzyme alone OR ES complex
Can’t be reversed by increasing substrate
What inhibition increases Km but Vmax stays the same?
Competitive
What inhibitor reduces Vmax but Km stays the same?
Noncompetitive
When does Km change?
Goes up with competitive inhibitor
When does Vmax change?
Goes down in presence of noncompetitive inhibitors
List some enzyme inhibitor drugs?
Statins, Beta lactams, Allopurinol, ACE inhibitors, aspirin
What happens to Lineweaver Burk plot in noncompetitive inhibitors?
Steeper slope is decreased Vmax ie 1/Vnaught increases
What happens to Lineweaver Burk plot in competitive inhibitors?
Same y-axis crossing with steeper slope which shows increased Km
What is salivary amylase?
Made in parotid- sensitive to radiation,
can be detected in blood but serum amylase is made by both salivary glands and exocrine pancreas Elevated levels mean acute pancreatitis
Amylase up with out lipase can mean stress or salivary gland inflammation
ALT/AST
Alanine Aspartate aminotransferases
Used in glycolysis
Plasma membrane damage and protein leakage increase levels
Testing monitors liver injury and disease
CPK?
Creatine Phosphokinase
Found in heart brain and skeletal muscles, leaks into blood when muscle tissue is damaged
Elevated levels indicate heart or muscle damage heart attack
Also high in lupus patients (joint pain and rash) shows muscle inflammation
Exercise and Statins increase it too
GALT?
Galactose-1-phosphate Uridyltransferase
Can’t metabolize galactose found in breast milk or dairy
Build up damages liver brain kidneys and eyes can cause them to vomit
Good to test newborns for
What are the key cells in chronic inflammation?
Macrophages
What do macrophages do to regulate chronic inflammation and immune response?
- Phagocytosis
2. Present antigens to T cells so B can make antibodies
What is the most prominent cell type in acute inflammation?
Neutrophils
Triple response of Lewis?
Constriction
Dilation
Edema/Swelling
What is a granuloma?
Large area of foreign bodies that macrophages have walled off from body.
Outer layer- macrophages, lymphocytes, plasma other inflammation molecules
Middle more macrophages aka lots
Center- necrosis
What is the most prominent cell type in acute inflammation?
Neutrophils
What do macrophages do to regulate chronic inflammation and immune response?
- Phagocytosis
2. Present antigens to T cells so B can make antibodies
What are the key cells in chronic inflammation?
Macrophages
What is a granuloma?
Large area of foreign bodies that macrophages have walled off from body.
Outer layer- lymphocytes, plasma other inflammation molecules
5 cardinal signs of inflammation?
Redness Heat Pain Swelling Loss of function
