Comprehensive Review of Bone, Enzyme, and Metabolic Disorders in Medical Science

Osteogenesis imperfecta

Collagen defect, affects all bony structures, brittle bone disease

Dentinogenesis imperfecta

Discolored teeth, obliterated pulp chamber, brittle teeth

Scurvy

A condition caused by a severe lack of vitamin C in the diet.o Bleeding gums, loose teeth

Absolute Specificity

Enzymes that are highly specific regarding which substrate they act on

Relative Specificity

Enzymes can catalyze reactions with molecules similar to the substrate

Salivary Amylase

initiates carbohydrate digestion in the mouth.o Acts on α-1,4-glycosidic bonds

Transition State

the peak of the apex

Zero-Order Reactions

Increase or decrease in A or B does NOT affect the rate of P. Traffic jam :: can't go any faster

First-Order Reactions

A → P Rate of reaction is directly proportional to the reactant.o Increase or decrease in A affects the rate of P

Second-Order Reactions

A + B → Po Rate of reaction is directly proportional to either reactant

Km

affinity of an enzyme for its substrate at one half of Vmax Higher Km, less affinity, more substrate is neededo Lower Km, higher affinity, less substrate is needed

Competitive Inhibitor

o Competes for active site, similar to substrateo Vmax UNCHANGEDo Km goes UP

Uncompetitive Inhibitor

o binds to ES complex and prevents it fromprogressing towards product.o Vmax goes DOWNo Km goes DOWN

Noncompetitive Inhibitor

o binds to an allosteric site on the enzyme.o Vmax goes DOWNo Km is UNCHANGED

β-lactam antibiotics / Penicillin

Binds irreversibly to transpeptidase (which makes up the peptidoglycan)

What is Ribose 5-Phosphate broken down into?

Purines and uric acid

What enzyme is involved in the breakdown of Ribose 5-Phosphate?

PRPP synthetase

How do purines regulate PRPP synthetase?

Through feedback inhibition via noncompetitive inhibition

What happens if there is a defective enzyme in the purine metabolism pathway?

It will keep producing uric acid, leading to crystal formation and an inflammatory reaction

Gout

Gout is a type of arthritis

crystal formation

R State

enzyme binds with more affinity but less stability to substrate

T State

Tight, enzyme bind with less affinity but more stability to substrate

T state is the default state

Concerted model

All subunits shift simultaneously from the T state to the R state

Sequential model

Enzyme can exist in a hybrid state

Hypophosphatasia

Disruption of mineralization of bones/teetho Can be caused by defective ALP

low activity of the enzyme alkaline phosphatase

Alkaline Phosphatase (ALP

Removes phosphates from molecules. Promotes HyAp formation '

Shut off by feedback inhibition of Pi

Ca and Pi can make

HA -> bone/teeth

Pyrophosphate (PPi)

o Hydrolyzed by ALP into 2 inorganic phosphates (Pi)

o Inhibits HA formation

Paget's Disease

o Osteoclasts go haywire

o Cotton wool appearance

Bisphosphonates

o Inhibit osteoclast activity

o Tooth extraction -> necrotic bone

ALP Blood levels

o Hypophosphatasia LOW ALP Paget's Disease HIGH ALP Bisphosphonates LOW ALP

Myoglobin

1 heme group
o Holds 1 oxygen molecule

Deoxygenated

Un-bound iron of porphyrin ring lies 0.4A below the plane.
o Contains a ‘pocket’, present in T state

Oxygenated

o Allosteric effect, iron atom is pulled back into the plane of the ring.
o Positive cooperativity, concerted model, when binds to O2, shifts to R state

2,3-BPG

Forces open the pocket, causing Hgb to shift to T state, dumping its O2 load
o 2,3 BPG gets released as Hgb travels back to lungs
o Smokers produce more 2,3 BPG, need more O to overcome 2,3 BPG

Hgb Tissue Side

o More acidic environment causes O2 to be released from Hgb.
o Co2 released by the cells, combines with water to make HCO3 and H. The H
forces the O2 off of the Hgb. The O2 gets picked up by the cells and the CO2, in
the form of HCO3 can now travel back to the lungs to be released

Hgb Lung Side

In the lungs, a basic environment and high O2 levels cause Hgb to bind O2. High O2 forces H+ off Hgb, which then combines with HCO3- to form CO2 for exhalation, and oxygenated Hgb goes to deliver O2 to tissues.