FOM Week 2 Flashcards
Factors Affecting Observed Rxn Rates
Energy/Temperature
Encounters/Concentration
Orientation
Transient State
The beginning of a rxn
All reactants and products are being changed
Equilibrium
When the rate of the forward rxn equals the rate of the reverse rxn. Occurs at the end of a rxn
Cells are never in equilibrium
Steady State
Occurs at intermediate time points
It is when one part of the rxn/cell is constant while everything else is changing
Examples of Irreversible Rxns
When a product is a gas
Proteolysis (they diffuse away from each other)
Properties of Catalysts/Enzymes
Lower the Ea to make rxns occur quicker Specific for certain rxns They are unchanged by the rxn Do not alter G or equilibrium Speed up both the forward and reverse rxn
Advantages of Enzymes
They increase the rate of rxns
They allow rxns to occur in gentle conditions
They can couple to drive non-spontaneous rxns by using the energy released from another rxn (hydrolysis of ATP)
They control the release of energy
What is included in the patient history interview
CC HPI PMH Meds All FH SH ROS
7 Characteristics of HPI
Where is it When did it start How bad What is it like When does it happen What helps What else
IHELLP for SH
Income Housing Education Legal Status Literacy Personal Safety
Fdel508 Mutation
Causes CF
A Phe gets deleted and this slows down protein folding which causes it to get degraded
Symptoms of CF
Causes a thick mucus build up in respiratory system
Malnutrition
Sometimes sterility
Kalydeco
A drug used to treat CF class 3 Will not work with Fdel508 because that is class 2
Pharmocogenetics
An individuals response to a drug may be different due to genetic differences
Peroxisome
Responsible for the metabolism of very long fatty acid chains through beta oxidation
Also responsible for the synthesis of plasmalogen
How are peroxisomes identified on EM
They have a crystalloid core in the center region
How are peroxisomes formed
Pre-perox proteins are made and then sent from the ER to fuse with other pre perox proteins or to join with existing peroxisomes. They then split in half
How are items transported into peroxisomes
The cargo gets tagged with PTS1 (c terminus) or PTS2 (n terminus)
The PTS protein then binds to PEX5 which will go into the peroxisome and then drop off the cargo
PEX5 then goes back into the cytosol and repeats
PPARs
Proteins that induce the transcription of pre perox proteins
They get very active when there are lots of FAs present in the cell or ECM
Skeletal muscle has lots of them. How exercise burns fat
X-ALD
An X linked disease
ALD is a transporter that allows FAs into the perox
The disease causes a build up of FAs
Treatment is diet plus Lorenzo’s oil
How are mitochondria identified on EM
They are long doubled membrane structures
Also by the cristae
Mitochondria Outer Membrane
It is very permeable and allows diffusion of many molecules
It causes the IM space to resemble the cytosol
Very important when it comes to lysosomes and oxidative phosphorylation
ATP Synthase
Is responsible for creating ATP through the H+ electrochemical gradient created by the ETC
Can also work backwards and pump H+ into the cytosol
Lysosomes
The recycling centers of the cells
Have a very low pH
How are lysosomes identified on EM
They are round and have lots of vesicles
How do lysosomes maintain their low pH
They have a V type ATPase that pumps H+ ions from the cytosol into the matrix (pH is around 5)
How are lysosome enzymes tagged for transport
A phosphototransferase places a P onto the oligosaccharide attached to the enzyme. This creates a M6P
Any enzyme tagged with M6P will bind to the trans golgi receptors and be shipped off to the lysosome
The receptor is then shipped back so it can be reused
I Cell Disease
Defective phosphototransferase so nothing gets tagged with M6P and the lysosomes cannot function
6 Classes of Enzymes
Oxidoreductase (involved in transfer of electrons)
Transferase (transfers functional groups)
Hydrolase (breas bonds by the addition of water)
Lyase (cleaves C-C, C-O, or C-N bonds w/o water)
Isomerase (rearrangement of atoms)
Ligase (forms C-C, C-O, or C-N bonds by ATP)
Oxidoreductase
Involved in transfer of electrons
Co enzymes involved are NADH, NADPH, FADH2
Common names are dehydrogenase, reductase, oxidase, peroxidase, CYP450
Transferase
Transfers functional groups
Common names are aminotransferase or kinase
Hydrolase
Breaks bonds by the addition of water
Common names are peptidase, esterase, protease, phosphatase, urease
Lyase
Cleaves C-C, C-O, C-N bonds
Common names are decarboxylase and aldolase
Enzymes that do the reverse are called synthases
Isomerase
Rearranges atoms
Common names are epimerase, racemase, and mutase
Ligase
Forms C-C, C-O, or C-N bonds by ATP
Common names are synthetases (not same as synthase)
CoFactors
Small metals that attach to the enzyme
Help to stabilize and also have a catalytic role
CoEnzymes
Vitamins that are essential for the enzyme to function
What groups do each of these molecules carry: ATP NADH/NAD+ NADPH/NADP+ FADH2/FAD
Carries phosphate groups which are high energy
Shuttles electrons used for fuel
Shuttles electrons used for biosynthesis and redox rxns
Shuttles elctectrons used for fuel (more powerful than NADs and work as prosthetic groups)
What groups do each of these molecules carry: Coenzyme A Biotin Tetrahydrofolate Adenosylmethionine
Acyl groups
CO2
1 C unit to another C or S
Methyl group to O or N
What groups do each of these molecules carry:
Pyridoxal Phosphate
Thiamine Pyrophosphate
Amine groups (NH2/NH) for a.a metabolism Aldehydes/ketones for decarboxylation
Cysteine Protease
Has an active SH residue
Ex are palpain and calpain
Inhibited when SH is modified (ex iodoacetamide)
Aspartate Protease
Active site requires a deprotonated Asp
Active at low pH
Ex are pepsin and HIV protease
Inhibited by pepstatin
Metalloprotease
Active site requires Zn or Co
Ca is sometimes needed for structure
Inhibited by EDTA which binds onto the Zn or Co
Serine Protease
Active site has a catalytic triad (Asp-His-Ser)
Threonine can substitute for Ser
Ex are trypsin, chymotrypsin, thrombin
Explain how the catalytic triad works
The OH on the serine attacks a carbonyl group forming a covalent intermediate
Water comes in to hydrolyze it and the enzyme goes back to normal
Assumptions of MM Equation
[Substrate]»_space;»»» [Et]
The rxn is in steady state
Rxn is irreversible once product is made
What will the rate equation be at very high [substrate]
V = K3 x [Et} = Vmax
Because the enzyme will be at Vmax
Kcat
The turnover rate of an enzyme
Kcat = Vmax / [Et]
MM Equation
V = (Vmax x [S]) / (Km + [S])
Km
The substrate concentration that gives you 1/2 Vmax
Km= (K3 + K2) / K1
Ways to Change Km
Temp
pH
Salt
Mutations
Way to Change Vmax
Add more enzyme
Change the Kcat
Why is it important to measure at the right time when doing a glucose test
If you wait too long you will get an artificially high reading
If you dont wait long enough you will get an artificially low reading
Types of Cell Adhesion Molecules
They are membrane spanning proteins that hold cells together and also are involved in cell signaling
They attach to the cytoskeleton using linker proteins
Integrins
Cadherins
Immunoglobulin
Zonula Occludens
A very tight junction that wraps around the entire cell
Prevents transport of all material
Cholera has a toxin that disassembles this
Proteins that Make Up the Zonula Occludens
Transmembrane linker proteins are Claudin, Occlaudin, and JAM-1
Plaque Proteins are ZO1, ZO2, ZO3
Filament it links to is actin
Zonula Adherens
Their purpose it to hold the cells together by providing structure and shape
They wrap all the way around the cell
Proteins that Make Up the Zonula Adherens
Transmembrane linker protein is cadherin
Plaque Proteins are alpha, beta, and gamma catenin, vinculin, and alpha actinin
Filament it links to is actin
Desmosomes
Their purpose is to give the cell extra strength to withstand friction
They have very thick plaque proteins
Dont wrap around the cell. Instead have spot welds
Proteins that Make Up the Desmosomes
Transmembrane linker protein is cadherin (desmoglein)
Plaque Proteins are plakoglobin (gamma catenin), desmoplankin, and plakophillin
Filament it links to is keratin (IF)
Gap Junctions
They are used for cell communication
Allow the diffusion of all molecules less than 1400 daltons
They have no link to the cytoskeleton
They are made up of connexins which form a hemi-pore
Hemidesmosome
A spot wield that links the epithelial to the BM
Autoimmune disease is called bullous pemphigoid
Proteins that Make Up the HemiDesmosome
Transmembrane linker protein is integrin and BP 180
Plaque Proteins are plectin and BP230
Filament it links to is keratin (IF)
Focal Adhesion
On the basal end of the epithelial
They are important for cell motility and signaling
Proteins that Make Up the Focal Adhesions
Transmembrane linker protein is integrin
Plaque proteins are vinculin, alpha actinin, FAK, SRC Kinase, Ras, Raf, GRB2, and SoS
Filament it links to is actin
3 Modifiable Determinant of Health
Socioeconomic environment
Physical Environment
Individual Behavior
Effects of Distress
Has a negative affect on health and behavior in most cases
Downward Drift Hypothesis
Mental disorders lead to reduced income and employment which in turn leads to more increased symptoms of mental disorders
Fundamental Attribution Error
An automatic way of thinking
We blame others wrong doing on internal behavior while our wrong doing due to external influences
Just World Hypothesis
People get what they deserve
Factors that Effect a Persons Pysche
Early trauma and stress Relationships Support Mental Disorders Behavior
Biopsychosocial Perspective
Seeing patients as whole persons
Not blaming the patient for what is wrong
Identifying which of the three will most help improve the patients health
Stages of Change
- Precontemplation
- Contemplation
- Preparation
- Action
- Maintenance
Relapse happens about 7-8 times and brings you back to steps 1-4
Etiology
The cause of a disease
Pathogenesis
The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent
Morphological Change
Structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process
Central Dogma of Pathology
Molecular damage–> Cellular damage–> Tissue damage–> Organ damage–> Clinical symptoms
VINDICATES
Vascular Infection/Idiopathic Neoplasia Drugs/Toxins Inflammation Congenital Allergies/Auto immune Trauma Endocrine Something else
Hypertrophy
Increase in cell size
Due to increased protein and organelle synthesis
Caused when the tissue is overworked
Ex is systematic hypertension
Treated with diuretics and ACE inhibitors
Hyperplasia
Increase in the cell number
Due to hormones and GFs
Ex is the breast and mammary glands during pregnancy
Atrophy
Decrease in both cell size and cell number
Caused when there is a lack of food/oxygen or when tissue is not active and an increase in protein degradation by proteosomes
Ex is Atherosclerosis
Metaplasia
When a differentiated cell type gets replaced by another cell type
Most common is columnar to squamous
Caused by a change in the stem cells below
Ex is Barret Esophagus
Dysplasia
Disordered growth of cells
Commonly seen in squamous epithelial
Is pre-malignant and needs treatment
Types of Loose CT
Aeriolar
Reticular
Adipose
Types of Dense CT
Regular
Irregular
Elastic
Types of Specialized CT
Bone (compact and spongy)
Blood
Cartilage (elastic and hyaline)
Types of Resident Cells
Fibroblasts
Chondroblasts
Osteoblasts
Ondontoblasts
Major Types of Collagen
Type 1 is found in skin and bone (most common)
Type 2 is found in cartilage
Type 3 is found in reticular fibers (liver, spleen, lymph nodes)
Type 4 is found in the basement membrane
Assembly of Collagen
The alpha chain is inserted into the lumen of the ER and the predomain is removed
Three precursors will then assemble into pro collagen where the NC1 domains are still present
The Procollagen peptidase then cleaves the NC1 domains from the collagen. This happens in the extracellular domain
The collagen molecules are then linked together to form collagen fibrils by the activity of LOX
The collagen fibrils then join together to form a collagen fiber
Ground Substance
The space between the loose CT
Is composed of water, proteoglycans, glycoproteins, and GAGs
Elastic Fibers
Made out of elastin and fibrillin
They are stetchy and return to normal shape
Found in organs that need to be flexible
Three Layers of BM
Lamina rara/lucida (made up of laminin) Lamina Densa (made up collagen 4) Lamina reticularis (made up of collagen 3)
Laminin
A protein secreted by the epithelial cells and binds to integrin on the basal side
Entactin
Joins the laminin to the collagen 4 in the lamina densa region of the BM
Proteoglycans
Bind to the laminin network and have sugars on them that hold signals to the underlying cell receptors
Isozymes
Enzymes that have similar functions but discrete differences
A way of enzyme regulation
Drugs can target multiple isozymes
COX1 and COX2
Inhibited by aspirin and ibuprofen
Inhibiting COX1 gives you the GI side effects
Ways to Change Enzyme Concentration
Synthesis
Degradation
Compartmentalization
Covalent Modifications to Enzymes
Phosphorylation (reversible)
Proteolysis (irreversible)
ATCase
An enzyme resonsible for synthesis of pyramidines
Activated by ATP and GTP
Inhibited by CTP and UTP
Ways to Regulate Enzymes
Isozymes Concentration Covalent Modification Cooperative/Allostery Co-Factors Availability Inhibition
Cross Sectional Study
A prevalence study that involves analysis of two data sets
It is convenient and cheap
Ecological Study
Monitoring data from cross sectional studies and placing them in populations or groups
Data is easily collected but gives rise to the ecological fallacy
Case Control Study
Starting with people who have the disease and working backwards in order to find the risk factors/cause
Is cheap and quick but you cannot determine prevalence or incidence from it
Cohort Study
Starting with people who are disease free and monitoring them when they are exposed to see who gets the disease
Costly and time consuming but gives you incidence
Randomized Control Clinical Trials
Planned experiments that assess the efficacy of treatments by comparing those with the treatment to those in the control group
Systematic Reviews
Combine and assess multiple studies in order to gain qualitative data
The most supported studies
Use Aspirin and Ibuprofen to Explain Reversible and Irreversible Inhibition
Ibuprofen is reversible from COX and readily dissociates
Aspirin is irreversible because it doesnt let go of COX and outlasts the life of RBCs
Categories of Irreversible Inhibitors
Drugs (penicillin)
Naturally occurring (serpins)
Heavy metals (mercury and lead)
Pathology (glycation of enzymes from diabetes)
Lineweaver-Burke Plots
Originally created before computers because quantifying date from curved plots was difficult
X axis is 1/[S]
Y axis is 1/Vo
Slope is Km/Vmax
How to Determine Km and Vmax from LB Plot
Where the line crosses x axis is 1/Km
Where the line crosses y axis is 1/Vmax
Competitive Inhibition
When the inhibitor competes with the substrate for the active site
Enzyme can bind one OR the other
Raises the Km but no effect on the Vmax
Non Competitive Inhibition
When the inhibitor allosterically binds to the enzyme or the ES complex and prevents the rxn from occuring
Lowers the Vmax but no effect on the Km
Uncompetitive Inhibiton
Affects both the Km and Vmax
Causes the lines to be parallel on the plot
AChase
Enzyme in the synapse that is responsible for hydrolyzing ACh so neurons arent always firing
Inhibitors of AChase
Carbomates are reversible
Sarin and malathion are irreversible
Myesthenia Gravis
A condition where the dendrites have too few of ACh receptors so the signals dont last long enough
Treat by adding carbomates to slow down degradation
Metabolism
All the chemical rxns that occur in a cell in order to maintain life
They involve a series of enzymatic processes
4 Building Blocks of Macromolecules
Sugars
Fatty Acids
Nucleotides
Amino Acids
What is the preferred energy source for most cells
Fatty Acids
Not ATP
Why is ATP the main currency of energy
It contains just the right amount of energy
It is stable
It is relatively small
Anemia
A disease caused from a patient having too few of RBCs
Erythrocytes
Red Blood Cells and are very short lived
They have no organelles and no nucleus
They are bio concave shape which is essential for flexibility
4 Major Steps to Tissue Preparation
Fixation (kills the cell but retains their shape)
Dehydration (all fixation and tissue fluid is removed)
Embedding
Staining
H&E Stain
The most common histological stain
H stains nuclei and ribosomes blue/purple
E stains collagen fibers red
PAS Stain
Stains a magenta color
Useful for observing mucins and glycogen
Trichrome Stain
Stains connective tissue a blue or green depending on the type used
Giemsa Stain
Stains a dark purple
Useful for observing blood cells and bone marrow
Toluldin Blue Stain
Stains mast cells a dark blue
Osmium Staining
Stains lipid rich areas such as myelin a dark black
Is also used for EM
