FOM Week 2

Use last names unless otherwise instructed

Upon entering the patient's room, prior to shaking their hands

• Chief Complaint (CC)
• (Other Active problems)
• Hx of Present Illness
• Past Medical Hx
• Family Hx
• Social Hx
• Review of Systems

In the patient's own words

Right after the CC and again after the HPI

Yes, pick about 3 problems to talk about--prioritize and negotiate with the patient

• Location: Where is it?
• Duration/Freq: When did it start?
• Severity: How bad is it?
• Quality: What is it like?
• Timing: When does it happen?
• Associated Symptoms: What else?
• Aggrevating/alleviating factors: What makes it better/what makes it worse?

History of Present Illness

Past medical history

The patient's immediate family and anyone who lives with them--looking for inheritable disease and illnesses affecting the family

Social History

To uncover additional information about other medical problems and the present illness

• Explanation: What do you think might be causing this?
• Treatment: Others they have tried/what do you want from me?
• Healers: Who have you sought advice from (social network)?
• Negotiate: Resolve with a mutually agreed upon plan
• Intervention: Letting the patient use safe alternative treatments
• Collagboration: with the pt and their social network, especially if working with a mental disorder

(in theory) a pool of dollars for a pool of people

Short

45 million

Employed

87%; premiums are increasing much faster than wages

insurance for children, women, and the very poor

Insurance for the elderly (>65) and the permanently disabled

health insurance, geographical, cultural, and language barriers

the access to care that affects important health outcomes (mortality, QOL, etc.); this shifts with time and is likely to become more patient centered in the future

COBRA, HIPPA, SOBRA, EMTALA

former employees can keep their insurance about 18 months after leaving or being let go

individual must be offerred at least 2 plans from each insurer

Medicaid for emergencies (eg. preggo women)

says that the ER must accept all patients

FQHC, hospitals, charity-funded clinics and government programs

• On a small scale it's rewarding (eg. pts and missions)
• On a large scale it's frustrating and complex

Focus on the underlying mechanisms so that you can predict the symptoms

• Vascular
• Infectious
• Neoplastic (cancer)
• Drugs or toxins
• Inflammatory/Idiopathic
• Congenital (gene abnormalities)
• Autoimmune disorder
• Trauma
• Endocrine/Metabolic
• Something else/supernatural/supertentorial

Physiological response of cells and tissues to trauma or disease

the cause is unknown

A definitive/absolute cause of the disease

To track the progression of changes in a disease to further understand so that they might be prevented in the future

Cellular dysfunction-->organ dysfunction-->clinical disease

Rudolf Virchow

increase in size of cell in response to energy

due to the syntehsis of more structural components within the cell (proteins and myofilaments)

No, can be pathological (hypertrophy of heart insystematic hypertension), but it can be good too (exercise--most common stilus is increased workload)

The nucleus becomes abnormally large, not centered and darkened; takes on a boxcar-like shape

Increase in the absolute number of cells in response to stimulus or persistent injury

No, example of the enlargment of breasts during pregnancy

tremendous proliferation of the glands; looks very similar to cancer

Shrinkage in the size of a cell (opposite of hypertrophy); may result in loss of function due to pressure, disuse (cast on leg), denervation, ischemia, or chronic injury

due to decreased protein synthesis (b/c of reduced metabolic activity) and increased proteind degredation in cells (via ubiquitin-proteasome pathway)

A reversible, induced change in the type of epithelium; commonly seen in smokers

Squamous cell carcinoma- the cells have gone through metaplasia and been altered to form squamous cells (abnormal in the resp. tract)

Stem cells or undifferentiated mesenchymal cells present are reprogrammed

disordered growth following chronic injury resulting in cells sloughing off more easily

in squamous epithelial cells

• Only dysplasia is pre-cancerous
• (metaplasia, hypertophy, hyperplasia, and atrophy are not)

loss of uniformity as well as architectural orientation, which is why it's precancerous

A carcinoma; the nuclei are not well-oriented,d arker, and there are more of them

Atrophy, hyperplasia, and hypertrophy

Apoptosis is programmed cell death of individual cells; necrosis is wide-spread, massive cell death

cells and extracellular matrix

fibers (collagen and elastin) and Ground Subtance (GAGs and associated protein cores)

In supporting tissues, basement membranes, cartilage, and bone

Thin sheets of ECM underlying all endothelial cells and epithelium

PAS (dyes the membrane purple)

Type IV collagen, heparing sulfate proteoglycan, laminin, entactin, and fibronectin

The lamina lucida and the lamina densa

Epithelial cells

laminin

• it is composed of 3 peptides: alpha (heparin binding site), gamma (proteoglycan binding site, entactin attachment site, integrin (cell surface receptor) binding sites), and beta (proteoglycan binding site, heparin sulfate bdingin site, integrin (CSR) binding site)
• This gives it the ability to bind to several different molecules and to itself to form the network that is the primary component of lamina lucida

the alpha and beta chains

the gamma chain

The gamma and beta chains

The gamma and beta chains

type IV collagen

The non-collagenous domain 7S (n-terminal), non-collagenous domain NC1 (c-terminal), and the triple helical collagenous domain in the center which is composed of 3 peptides

Because the non-collagenous domains are not cleaved off, as they are in the other types. This prevents interactions between collagenous domains

• Anti-parallel connections (7S domain connects to 4 collagens) and
• Head to head connections (NC1 domains connect 2 collagens

Lamina lucida (rara), lamina densa, and lamina reticularis

in the underlying connective tissue (mostly by fibroblasts)

The lamina reticularis would be synthesized incorrectly, or not at all

the lamina reticularis

reticular fibers which are formed by collagen III

in the kidneys

To serve as a filtration barrier

Although it is composed of only the lamina densa and the lamina lucida, it is still referred to as basemement membrane

fusion of epithlial and endothelial cells

thickening of the membrane due to inability to process glucose-->excess glucose in the blood-->AAs in tissue interact with glucose to form highly reactive O2 intermediates-->react with proteins in the BM to form advanced glycated ends (AGE)-->bind to RAGE-->signals a change in gene activity to create more BM

They are degraded slower than normal proteins, resulting in a buildup and decreased formation of normal proteins

advanced glycated ends; formed from interactions between AAs in the tissue and excess glucose

Entactin binds the collagen via the C-termini domains an the laminin via the entactin binding sites on the beta chain

Integrins bind to the long arms of the beta and gamma chains on laminin and acts like velcro; these integrins then bind to attachment proteins that are connected to the actin cytoskeleton of the cell

The connection between the attachment proteins and the integrins allows teh cell some movement

the skin sloughs off because of mutations in integrins or laminin chains; there is detachment of the epithelium from the BM; almost always perinatally lethal

An autoimmue disorder in which hemidesmosomes are targeted by the body (specifically by BP180 and BP230); inflammation occurs at dermal-epidermal junctions; benign; affects older people

an autoimmune disorder in which the desmosomes are targeted (specifically by desmoglein); skin sloughs off because things holding the cells side by side ripa apart; this is a disorder with the epidermal-epidermal junction

pemphigus vulgaris

bullous pemphigoid

• Junctional epidermolysis is a defect with the integrins or laminin chains, whereas bullous pemphigoid is a defect with the hemidesmosomes
• Subtle difference, similar clinical presentation

at the C-terminal (NC1) end of collage; this is a dimer formed by disulfide bonds on the collagen

contains a collagen binding domain and a cell binding domain (through the integrins)

they bind to the laminin network; specifically, the GAG side cahin (heparin sulfate) binds to alpha and beta chains of laminin

The GAGs have long and highly negative arms that function to sequester growth factors from the ECM

To store fat in the form of triglycerides

Connective tissue

White adipose tissue (WAT)

• insulation (conducts heat only 1/3 as readily as other tissues)
• shock absorption (surrounds all major organs)
• energy storage (buffer for energy imbalances)

• Because the carbons of fatty acids form high energy bonds (contain about 9 cal/gram)
• Also because the triglycerides are stored with very little water

in fetuses and infants; diminshes after the first decade

Brown adipose tissue

• important in regulating body temp (generates heat via thermogenesis)
• direct release of energy as heat (lipids do this instead of being used as a substrate)

They utilize the uncoupling protein (UCP-1) of mitochondria to transfer protons from outside to inside without the production of ATP

loose association of lipid-filled cells that comprises the major bulk of adipose tissue in all adult mammals

BAT although each adipocyte of WAT is in contact with at least one capillary

No, the number of adipocytes increases through development and then remains constant through life; the size of each adipocyte can change

fibroblast-like precursor cells (mesenchymal cells) differentiate into preadipocytes with the expression of PPAR. These preadipocytes contain insulin growth factor-1 (IGF-1) and begin to synthesize lipoprotein lipse (LPL) and accumulate small fat droplets in the presence of insuling. These can then differentiate into WAT or BAT

single lipid droplet that pushes the cell nucleus and mitochondria against the plasma membrane; gives the cell a characteristic signet shape; predominantly in the WAT

Containing many smaller droplets of lipids; predominantly in the BAT

the depsoition of fat

in adipose tissue, triglycerides are hydrolyzed to glycerol and free FAs by lipoprotein lipase; these free FAs are then taken up adipocytes in a concentration dependent manner by a transport protein; FAs combine with CoA to form a thioester and are re-esterized to form triglycerides

Glucerol

• enhances storage and blocks mobilization and oxidation of FAs by stimulating lipoprotein lipoase formation
• Also required for transport of glucose

decomposition and release of FAs from the adipose tissue

the multi-enzyme complex HSL (hormone sensitive lipase) hydrolyzes triglyceride into free FAs and glycerol

It inhibits through the inhibition of the hormone sensitive lipase (HSL) enzyme

25

30

1.6 billion

400 million

A glycine present at every third AA produces this structure

Glycine, proline, hydroxyproline

• all collagens are syntehsized with 2 non-collagenous domains--to produce the collagen fibrils, non-collagenous domains must be removed
• They are synthesized as individual chains called procollagen which contain registration peptides within the cell. These are then secreted to the ECM where procollagen peptidases cleave the non-helical registration peptides to produce insoluble tropocollagen; aggregation of tropocollagns form collagen fibrils and covalent cross-linking between these reinforces the fibrillar structure

help assemble and regulate the procollagen into the triple helical molecule

the overlap of tropocollagen

Similar to the size of a fibroblast

type I

irregular connective tissue composed primarily of type I collagen

to support tubes especially in the linin gof the GI, GU, and respiratory tract; contains a lot of Type I and ground substance

networks of fibrils, not fibers

in the cartilage (but most abundantly in the hyaline and elastic)

Type III forms reticular fibers which are very different from the collagen fibers found in type I

In the lamina reticularis

forms the supporting framework for many highly cellular organs such as the spleen and lvier

forms networks with no fibers or fibrils because the non-collagenous parts are not cleaved off

In the basement membrane

To provide elasticity and stretching to tissues

the cross-linking between individual elastin molecules

Both; most commonly fibers, but elastic sheets are found in the walls of large blood vessels

tropoelastin, fibrillin I, fibrillin II, and microfibril associated protein (MAGP)

to provide the force and structural support

to regulate the assembly of said fiber

• Primarily synthesized by fibroblasts and smooth muscle cells
• Proelastin is formed in the RER from desmosine and isodesmosine; all components of the elastic fiber are then secreted to the ECM (proelastin secreted by the GA); coassembly of MAGp and tropoealstin to produce the immature elastic fibers; these bundle together to form mature elastic fibers

Synthesis of the components occurs in the cell (RER); components are secreted to the ECM where they are assembled

Fibrillin I is deficient. Because of this, elastic fibers cannot be synthesized because there's no structural support

mitral valve prolapse (flap goes down into ventricle instead of coming up like in normal patients; basically, the seal is no good) and aortic dissection

Autosomal dominant (but the good gene still can't produce enough)

Chest deformity, tall, long arms, arachnodetyly

• degrade ECM proteins to help cells
• involved in embryonic development, tissue morphogenesis, wound repair, inflammaotry diseases and cancer

metal ions

Epithelial cells or cells moving in and out of the ECM

• Proteolytic activation
• Proteolytic processing and inactivation
• Protein inhibition (by tissue inhibitors of MMPs called TIMPs)
• ECM localization (bound by stuff in ECM to keep it there)
• Cell surface localization (by receptors)
• Endocytosis and Intracellular degredation

They are overexpressed in tumor cells to degrade the basement membrane and other structural proteins in teh underlying connective tissue

Connective tissue cells

Resident cells, which are a type of connective tissue cell

To synthesize proteoglycans, collagen, and elastin

Fibroblasts that syntehsize type III collagen in bone marrow and lymphoid organs

fibroblast equivalent in cartlage--synthesize type II collagen

fibroblast equivalent in bone--synthesizes type I collagen

fibroblast equivalent in teeth (dentin)--synthesizes type I collagen

in epithelial cells

Usually the only thing you can see is the nucleus because the cytoplasm is squeezed long and tight to make connections with other cells

Macrophages, lymphocytes, plasma cells, mast cells, and eosinophils

to phagocytose anything foreign in the ECM; literally "big-eater"

dark blue because of the phagocytic vesicles inside

in the GI tract

A plasma cell

No, almost quiescent

• It is the mechanism by which lymphocytes move through the connective tissue
• Cells interact with receptors (selectin) on endothelial cells weakly. Lymphocyte rolls along the surface until it interacts tightly with integrin and then passes in between the cells into the ECM

It actively synthesizes antibodies (proteins or immunoglobulins)

• Off to the edge
• Characteristic cartwheel configuration is created by the distribution of heterochromatin

Mast cells

When an antigen cross-links 2 IgE antibodies on the surface of the mast cell, a movement of cystolic Ca2+ is initiated; this triggers the release of granules storing histmine, proteases, and proteoglycans; cytokines are also synthesized and released into the local environment

The block the effect of the histamines released from the the mast cell, but they do not interfere with the release of it

An eosinophil

• Eosinophil peroxidase (binds to microorganisms and helps macrophages kill them)
• Major basic protein (MBP) (binds and disrupts parasitic membranes)
• Eosinophil cationic protein (works with MBP to fragment parasites)

a fibrin clot is laid out to stop the bleeding; cytokines recruit macrophages and fibroblasts via diapedesis; these cells are attracted to the ligand EN-RAGE; the recruited fibroblasts degrade excess MMPs and synthesize collagen to heal the wound

AGE (the highly reactive proteins) are everywhere; these compete to make tissue like glue so that the fibroblasts can't get to the wound site; as a result, the connective tissue is further destroyed (by MMPs), the wound won't heal, and it just keeps getting worse and worse

Involved in the tight packing of actin fibers (parallel bundles)

Involved in the loose packing of actin fibers (contractile bundles)

The GTP cap is used to stabilize microtubules while the Cap Z is used to stabilize actin filaments

Filopodia and lamellopodia (respectively)

Actin filaments

cytoplasmic motors

Na+, glucose transporter

Moves 3 Na+ molecules into the blood and 2 K+ molecules into the intestinal epithelial using the energy from hydrolyzing ATP

The diffusion of K+ out of the cell

to move glucose from the intestinal epithelial cells into the blood

• They use passive facilitated diffusion
• They have bi-directional transport because glucose is travelling tothe lowest concentration (passive)
• They require a sugar gradient
• Stereoselective for Glucose

• Substrate specificity
• Substrate Km
• Tissue distribution
• Regulation

• High glucose concentrations within the cell won't saturate GLUT2 and it keeps operating
• Takes a long time to reach saturation of transporter

fructose

It is translocated to plamsa membrane

a secondary active transporter, meaning that it uses Na+ transport (with gradient) to drive glucose transport (against gradient)

It's a 6 step process

• Intracellular: plasma concentration
• Na+ 10:142
• K+ 140:4

Pore, channel, and pump/transporter

both ends of passage are open always

• both ends of channel are open during passage (fast process)
• Channel opening can be regulated
• Ion channels have smaller pore sizes

only one end is open during passage at any time; analagous to an air lock; binding causes a conformational change

A pump has slow movement of ions against a gradient and requires ATP; a transporter also has slow movement of ions, but it is driven by a gradient and may or may not require ATP

The transporter works with a gradient and experiences a conformational change upon binding

12

It contains 12 transmembrane alpha-helices (don't know a lot)

In the liver, kidneys, islets, and small intestine

17 mM, signifies that it does not ever get saturated as the normal circulating glucose concentration is 3.6 to 5.6 mM

To move glucose from the cell to the blood

It releases insulin in a 1:1 ratio

3-7 mM; this is involved in basal glucose uptake and transport across blood tissue barriers

1.4 mM; found in the brain and nerve cells; needs to be low because brain has high demand for glucose, don't want to lose it in the blood

Insulin and muscle contraction (which is why it's important to exercise); involved in translocation from vesicle to plasma membrane

GLUT4 and mRNA are reduced in adipose tissue of diabetic animals

At least 6 isoforms

in the kidney and intestines (in the epithelial cells); it functions to reabsorb glucose into the kidneys and intestine

in the kidney; it has a low affinity and high selectivity for glucose

They prefer to move glucose into the cell, but they can be bi-directional

There is more water in the lumen of the gut because glucose isn't absorbed out of the gut and water prefers to stay where glucose is

They cannot absorb glucose into the cell from the gut properly. Give them fructose as a dietary alternative

Sodium is not taken up and builds up in high concentration in the urine. More water goes there (produces more urine, polyurea) and the patient is frequently thirsty. Large amounts of glucose are also excreted although there is no change in blood glucose levels

It drives the SGLT into action and more sodium and glucose is moved into the cells. Consequently, more water is also moved into the cells

Ion gradients

Because the transporters work together and knocking out one will likely affect several others

always open

It responds to changes in membrane potentials

It responds to extracellular neurotransitters

It responds to intracellular signal transduction events

They have arms in the center that move and cause a conformational change when there is a change in electricl potential

Sodium potassium ATPase

Sodium, potassium ATPase; it uses 1/3 of cell's ATP to maintain this gradient

cardiac glycosides like digoxin; leads to slower, stronger heart contractions

• P-Type ATPase (ion transport including Na+ K+)
• F and V-type ATPase (sets up the H+ gradient in metabolism)
• ABC superfamily (transports ions, peptides, lipids, and drugs)

48

4, 2, or 1 polypeptide subunits with 2 TM domains (not conserved, specificity for different ligands) and 2 nucleotide binding domains (bind ATP to cause conformational change, Walker A is a good example of this)

4 (steps 1 and 4 are the same....so maybe just 3)

They are hydrophobic

An MDR transporter is a multi-drug resistant protein. It probably evolved to protect the cell against toxins that freely diffuse in; these nonspecifically transport lipophilic, planar molecules out of the cell

All families, not just ABC

ABC superfamily

MDR (multidrug resistant) or ABC (ATP binding cassette)

It is mostly composed of product

It is mostly reactant

Drives the reaction to proceed toward equilibrium

• deltaG=deltaH-TdeltaS
• G=H-TS

• It tells youthe direction the reaction will occur.
• Negative reactions proceed forward and are spontaneous.
• Positive are not spontaneous and likely will not happen

Delta G determines what actually happens whil delta G not refers to the standard state

delta G not=-RTln(Keq)

The transition state or the activation energy, enzymes work by lowering the energy of activation

• K1 is the rate of the forward reaction, K2 is the rate of the reverse
• The velocity of the forward reaction=K1[A][B]
• The velocity of the reverse reaction=K2[C][D]

energy, encounter, and orientation

The brief period when the reaction has just started

• a situation where all state variables are constant, but equilibrium has not yet been reached
• Our bodies are in steady state because we do not reach equilibrium because of constant replenishing of reactants and removal of products

• Highly specific
• Unchanged in the reaction
• Only required in trace amounts (because not used up)
• No change in Keq
• Only change rate constants
• Allow for a controlled release of energy
• Charged side chains often predict pH sensitivity

Depends on the number of products and reactants. For 2 react, 2 prod, there are 4 enzyme substrate complexes (EA, EAB, ECD, EC) and each one represents a transition state (though none of these transition states are equal to the uncatalyzed transition state activation energy

They are coupled to favorable reactions

• It is independent of the pathway it took to get to the final product
• Cares only about the distance of the energy between the first reactant and the final product

Use diaminobenzidene plus H2O2 because it forms an electron dense precipitant in the peroxisome

• Ether lipid synthesis
• beta-oxidation of fatty acids
• alpha-oxidation of fatty acids

Demylination in the brain

The ability to digest more fat

in the ER

• A protein must have the starting sequence of serine-lysine-leucine; if this sequence is present, it will bind to complex 5 which transports it inside the peroxisome where the pH change causes the protein to release and 5 to come back out
• This starting code is called the peroxisome transport signal 1 (at the C-terminal)

• Peroxisome proliferating activating receptor
• incerases the number of peroxisomes by increasing the number of times they divide
• PPAR binds to free fatty acids and DNA to signal proteins to make more peroxisomes
• Activation of a PPAR leads to burning more fatty acids and less glucose

• Exercise increases
• Age decreases
• Short term fasting increases
• Long term fasting decreases

Type II diabetes

• the ABCD gene (ATP dependent protein that pumps fatty acids into peroxisome)
• This is a spectum disorder
• Patients can't pump fatty acids into peroxisomes, so they build up in the blood and cytosol and knockout the adrenal glands; also leads to problems with myelin formation and retardation
• TMNT: diet control

• In long chains
• Have an inner membrane, outer membrane, intermembrane space, and matrix (which is broken up by stacks of inner membrane)

the extensively folded flat structures of the inner membrane within the mitochondria

in the space between the inner and outer membrane. Formed by the electron transport chain

The energy from the electrochemical gradient turns the rotor handle and phosphorylates ADP

~1000

La momma mia

the mitochondria

Lysosome

V-type ATPase

• nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases, phspholipases
• All function best at low pH (inactive when transpored through cytosol because pH is 7.0)

• receives incoming endocytic vesicles
• Sorts for recycling and degredation

Early endosome (formed from pinched off membrane)-->late endosome-->lysosome

Contains intraluminal vesicles (ILV) which ubiquinate proteins that are not destined to be recycled and targets them for the lysosome

The lysosome to be degraded

To the lysosome

In the lysosome

acidic vesicles in the cytoplasm that are full of hydrolytic enzymes; functions to hydrolyze macromolecules to monomers and recycle subunits

• 40
• diseases typically result from lack of a particular enzyme in the lysosome; lysosome can't break down a particular component and it builds up over time; symptoms vary depending on which component it is; worst is I cell disease

Manose-6-phosphate shuttle does not work and garbage and debris cannot be shuttled into the lysosome. This is the worst of the lysosomal diseases because none of the enzymes within can work and debris builds up. Results in demylination and death within the first few months

Oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases

• Reduces one compound to oxidize the other (redox reactions)
• NADH, NADPH, FADH2

Transfers a component from one substrate to another

• Splits water to carry out some type of chemistry
• H2O will ALWAYS be involved

Cleaves C-C, C-O, C-S, and C-N bonds by means other than oxidation or hydrolysis

Only rearrangement of the atoms, none added or lost

• forms C-C, C-S, C-O, and C-N bonds using the energy from ATP hydrolysis; doesn't transfer the phosphate, just uses the energy
• ATP or GTP will ALWAYS be involved

A kinase is a transferase, so it transfers one chemical group to another compound; specifically, it transfers phosphate groups from ATP

structural and co-factor

Yup

Carries phosphoryl group (very high energy bond) for protein phosphorylation

Shuttles electrons for redox of biological fuels, helps produce ATP

Shuttles electrons for the redox of biological fuels (more powerful than NAD); always bound to a protein

Carries an acyl group

Carries an aldehyde for decarboxylation

Carries a CO2 for carboxylation

in amino acid metabolism, it carries one carbon unit to another carbon or a sulfur

Carries a methyl to oxygen or nitrogen

In amino acid metabolism, it forms a Sciff base with many amine compounds, forming a key intermediate in AA metabolism

Cleave peptide bonds, found everywhere, classified by which amino acid side chains or metals are located in their active site

A serine protease. There is a serine residue in it's active site. It works by forming an acyl enzyme (covalent intermediate) and then hydrolyzing the acyl enzyme

• Bind more tightly to the intermediate than to the reactants or products
• Strain the reactant to look more like the transition state
• Trap 2 reactants close to each other
• Orient the two reactants so the proper regions are juxtaposed

• that the enzyme is saturated [S]>>>>[E]
• that the reaction is in steady state
• and because it measures only the early (linear) times, that the reaction is irreversible

k1[E][S] = (k2 + k3)[ES]

Vmax=k3[ES]

Where k3 is the rate from ES to E + P

• k4
• the rate from E + P to ES

• Km= (k2 + k3)/k1
• additionally, Km=[S]([Et]-[ES])/[ES]

Vnot= (Vmax*[S])/(Km +[S])

At half Vmax, Km = [S]

Velocity is maximal

The velocity decreases to a minimum

• X-intercept= -1/Km
• Y-intercept= 1/Vmax
• Slope is Km/Vmax
• Where x-axis= 1/[S] and y-axis=1/(Vnot)

• Isozymes
• Enzyme concentration
• Covalent modification
• Cooperativity/Allosteric Regulation
• Linked enzymatic Reactions
• Substrate/co-factor availability
• Inhibition

Isozymes are slightly different forms of the same enzyme with the similar function. Different isozymes have different enzymatic activity in different tissues due to specificity of the active site

changes in gene expression and enzyme degredation

Phosphorylation and proteolysis

metabolic pathways

reversible enzyme inhibition

Irreversible enzyme inhibition

Serpin and heavy metals (non-specific binding to side chains that mimics other co-factors; tmnt is chelation)

• Competitive inhibitors alter the x-intercept, or the 1/km
• Non-competitive inhibitors alters the slope, or Km/Vmax because X binds to both free enzyme and the ES

only ES complexes

free enzymes and ES complexes

it decreases Vmax

Nothing, the degree of inhibition is based solely on the concentration of the enzyme

Km will increase because the inhibitor competes with the substrate to get to the active site; more enzyme will be in the ES complex because more substrate is present

In locations remote from the active site

Competitive inhibitors resemble the structure of the substrate, so increasing the inhibitor concentration increases the time it takes for half the enzyme to be bound. Vmax remains unchanged because increasing the substrate concentration allows the substrate to overcome the inhibition and reach Vmax.

The peroxisome. Peroxisomes are the sole site of plasmalogen synthesis (which is a glycerol-based phospholipid).

the matrix

Tay-Sachs disease is a lysosomal storage disease. Hexosaminidase A is deficient, resulting in the buildup of GM2 ganglioside and leading to mental retardation, blindness, and mortality. The best treatment would be to stimulate hexosaminidase production

laminin of the lamina lucida

Type IV collagen

The highly charged GAGs

The presence of Na+, K+-ATPase

apical and lateral

the apical and the basolateral

The apical

Kinesin

Troponin

• zonula occludens
• zonula adherens
• macula adherens (desmosomes)
• Gap junctions
• Hemidesmosomes
• Focal Adhesions

zonula occludens

zonula adherens

Desmosomes (macula adherens)

A gap junction

Hemidesmosome

Cadherins

Cadherins, immunoglobulin family of CAMs, and integrins

• Structurally link the cell to the outside
• Cell signalling complexes

Cadherins

homophilic, heterophilic, and extracellular matrix linkages

The zonula occludens

occludin (utilizes ZO-1 as the main intracellular plaque protein) and claudin (utilizes ZO-2)

The Zonula Occludens toxin disrupts the Zonula Occludens

Cadherin

Vinculin

Desmosomes

Cadherins

Desmoplakin