exam 2 Flashcards
what is oxidative stress?
body’s inability to readily detoxify a reactive metabolic intermediate or repair tissue damage resulting from an imbalance in oxidation/reduction and formation of ROS
disturbance in equilibrium status of prooxidant.antioxidant systems in intact cells
What is ROS?
reactive oxygen species
what are three neuronal disorders with oxidative stress component
Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease, and Parkinson’s Disease
What is the most common form of adult-onset dementia?
Alzheimer’s disease
Which disease is prevalent in those >65 yoa?
Parkinson’s Disease
which two neuronal disorders are mechanisms of neuronal death?
Alzheimer’s Disease and Parkinson’s Disease
Which disorder has a defective SOD enzyme?
Amyotrophic Lateral Sclerosis (ALS)
What are the free radicals?
hydroyxl radical, peroxyl radical, carbon radical, alkoxy radical, nitric oxide, thiyl radical, superoxide (HPCANTS) :
aka harry potter can’t sometimes
What are non-radical species? (stable compounds free radicals transform into0?
peroxynitrite, ozone, singlet oxygen, hydrogyen peroxide, lipid hydroperoxide, hydrochlorous acid
POSO
POSOHPLHHA
What is SOD?
- superoxide dismutatse
- most important endogenous antioxidant
- enzyme used by biological systems to remove the toxic superoxide radical
- it catalyzes the dismutation of superoxide anion to maintain a low concentration of it
its absence: lethal
overload: detrimental bc excess may produce hydrogen peroxide at rate toxic to cells during oxidative stress
What does the fenton reaction entail?
-involves one of the most powerful oxidizing reactions available
Peroxide is broken down into hydroxide ion and hydroxyl free radical.
What is H2O2?
hydrogen peroxide
What does it mean that oxygen is biradical?
two unpaired electrons unlikely to participate in reactions with organic molecules unless it is activated
What is the catalase reaction?
2H2O2 —-> 2H20 +O2
What is the difference between arteriosclerosis and atherosclerosis?
ateriosclerosis is the degeneration of the arteries, resulting in thickening and hardening of the arterial wall
atherosclerosis is the SPECIFIC form of arteriosclerosis, an accumulation of lipids in lesions of intima of large and medium sized arteries
difference between CHD and CVD?
CHD: coronary heart disease, any disorder that results from inadequate blood circulation to the heart, impairing heart function
CVD: broader category, any disorder that results from inadequate blood circulation in heart, brain, neck and extremities, often due to plaque buildup
what is angina?
chest pain resulting from arteries that are narrowed by 50%+, reducing blood supply to the heart
referred pain felt in different parts of the body, radiating from the left shoulder and arm
what is heart disease by definition?
a collection of disorders that result in inadequate blood circulation to the heart
What is an aneurysm?
dilation or ballooning of an artery
How is ischemia related to angina?
deficient blood supply of ischemia causes angina because the arteries are narrowed by more than 50%
What is an infarct?
area of coagulation necrosis due to deficient blood supply.
In a myocardial infarction (heart attack), part of heart dies due to inadequate blood flow
what is an cerebral infarction?
stroke
What is a myocardial infarction?
heart attack
What is an infarct in extremities?
gangrene
What is stenosis?
narrowing of a vessel
what is an embolus?
a plug, composed of a detached clot, mass of bacteria, or other foreign body, occluding a blood vessel
What is a thrombus?
a blood clot which more or less occludes an artery or cavity in the cardiovascular system, a specific type of embolism
Can a heart attack occur form both thrombus or embolus?
yes
What are the four kinds of human plasma lipoproteins?
vldl
hdl
ldl
chylomicron
what is the general structure of a plasma protein
- complex of protein, phospholipid, cholesterol
- proteins may be integral or peripheral
- very complex micelle – monolayer, not bilayer like a membrane
- used to transport lipids in blood from one site to another
- several types of lipoprotein complex
apoproteins triaglycerol cholesteryl ester cholesterol phospholipid
why is cholesterol packaged?
it is not water soluble and must be packaged into lipoproteins in order to be transported
what is less dense than both cholesterol and water?
fat as a triglyceride is much less dense than both cholesterol and water. The lower the triglyceride level, the higher the density.
what is tumor suppressor gene?
gene encoding negative effectors of growth “the brakes”
oxidative stress?
damage to cells and other cellular constituents and processes by ROS generated
tumor/tumorigenesis?
new growth of tissue in which the multiplication of cells in uncontrolled and progressive
toxicant?
man made chemical that may or may not cause cancer
xenobiotic?
general term used to describe any chemical interacting with an organism that does not occur in normal metabolic pathways of that organism
three steps of cancer
initiation
promotion
progression
what is initiation?
start of cancer process, alteration of dna in cells due tp exposure to environmental toxins, contaminants or other chemical agents
What are the two phases of biotransformation?`
phase I: a functional group is introduced into molecule by oxidation, reduction or hydrolysis
phase II: conjugation of an absorbed material or its metabolite with an endogenous substrate
what is the p53 gene?
tumor suppressor gene
superoxide dismutase
involved in identifying mutations and then fixing them in dna
EDITING SEQUENCE
can initiate apoptosis, programmed cell death, if dna damage proves to be irreparable
risk factors for p53 mutation
physical inactivity
large bmi
smoking
western stle diet high in red meat and simple sugars
if something is genotoxic, it is—
dna damaging
what is microbiome?
collectively all the microbes in the human body; a community of microbes
what is the ciliary escalator?
physical barrier to pathogen
push away and brush off bacteria
secretes mucous against foreign molecules
largely prevents unwanted bacterial colonization
major barriers for microbes entering the gut?
Saliva and bile
Low pH
Immune system
Finding a place to attach to intestinal wall
surviving a widely varied diet
What are the benefits to the host that the symbiotic bacteria provide?
nutrient supply, pathogen defense, immune system development/function
what does the brain influence in the intestinal microbiota?
physiology epithelial function mucin production ee cell function motility
What is the influence of the microbiota on the brain and hehavior?
activation of neural afferent circuits to the brain
activation of mucosal immune responses
production of metabolites that directly influence the CNS
what are the two types of bacteria to know?
bacteriodetes and firmicutes at phylum level
what happens to mice that are germ-free?
leaky gut that promotes for inflammation reduced food intake increased fecal lipid excretion resistant to weight gain underdeveloped immune system greater anxiety-like behaviors
link between gut microbiome and what disorder?
autism/schizophrenia
what are the requirements for activation?
two unpaired electrons have parallel spin and must have absorption of sufficient energy to reverse the spin on one of the unpaired electrons or monovalent reduction (transfer of a single electron)
what is pauli’s exlcusion principle?
pauli’s exclusion principle inhibits reactions with a divalent reductant, unless the reductant also has parallel spins opposite to oxygen, which is rare. Spin restriction means that the most common mechanisms of oxygen reduction interactions only involve transfer of a single electron (monovalent reduction)
what is the singlet state?
two electrons have opposite spins because triplet oxygen absorbs sufficient energy to reverse the spin of one of its unpaired electrons
more reactive toward organic molecules than triplet counterpart because paired electrons are common in organic molecules
what is triplet state?
biradical form of oxygen in a triplet ground state because the electrons have parallel spins
what is oxidation?
loss of electrons or increase in oxidation sate
what is reduction?
gain of electrons or decrease in oxidation state
what is a free radical?
chemical missing an electron; absence of electron makes chemical reactive and prone to oxidize (steal electron from) a nearby atom or molecule
what is an antioxidant?
substance that prevents or repairs damage to cell caused by exposure to free radicals by donating its extra electron
what are the antioxidants?
beta-carotene, vit e, vit c, selenium
what antioxidants are water soluble?
Vitamin C and selenium
what antioxidants are fat soluble?
beta carotene and vitamin e
which antioxidants are the ideal?
vit c and e
which antioxidant has the easiest toxicity?
selenium, but also not desirable to have beta carotene because of foods like carrots can turn your subcutaneous tissues that color in almost toxicity levels
beta carotene is not a nutrient but is a precursor for which vitamin?
vitamin A, two vitamin A’s linked together with extra electron but exists in that form and doesn’t break apart. once donated, becomes two separate vit a compounds
beta carotene is an antioxidant but vit a alone is not
why are we constantly at flux and rarely at equilibrium at oxidative and reductive states?
we constantly promote for free radical damage independent of diet, and also poor western diet
name some ROS/Oxidative stress effects
premature aging neurological damage viral replication immune dysfunction programmed cell death
enemy for proxidant effects?
pesticides
polyunsaturated lipids (30%+ is risk)
plan toxin
what are prooxidants?
chemical compounds and reactions capable of generating potential toxic oxygen specices
anti-oxidant
chemical compounds and reactions capable of disposing of these species, suppressing or opposing them
what is a xenobiotic?
any foreign chemical interaction that does not occur naturally
what are the exogenous sources of oxidative stress?
xenobiotics, pollution, pesticides, hyperoxia, ozone
what are endogenous sources of oxidative stress?
mitochondria, phagocytes, peroxisomes
what is catalase reaction?
2H2O2 —-> 2H2o + O2
what is superoxide dismutatse sod?
2O2- + 2H+ —–> H2O2 + O2
what is fenton reaction?
most powerful oxidizing reaction
hydrogen peroxide and ferrous iron catalyst
peroxide broken down into a hydroxide ion and hydroxyl free radical
h2o2 —-> OH + OH-
what are the lipoproteins that contain endogenous choleesterol?
IDL and LDL
What does very low density lipoprotein do?
transports mostly triglyceride, some cholesterol from liver to the periphery
chylomicron does what?
it transports dietary triglyceride form gut to the liver and carries dietary triglyceride
chylomicrons and vldl’s deposit triglycerides into where?
lipid droplet of adipocytes
liver makes ldl and goals is to take excess cholesterol from there and deposit it where?
peripheral cells
LDL is derived from where?
VLDL
LDL comes from VLDL but what do they carry?
LDL – cholesterol
VLDL – triglycerides
Explain LDL receptor and cholesterol uptakes
LDL receptor is glycoprotein that binds LDL and starts cascade effect
Region with receptors is called a “coated pit” coated with a protein called clathrin
LDL binding to receptor pinches to form a coated vescle, and clathrin coming off is uncoated – only comes off from ATP proton pump and pH change
the uncoated fuses to lysosome for degradation of LDL to cholesterol and amino acids
Without sufficient ldl receptors, ldl remains in the blood – scums up arteries
Why do you need ldl receptors?
LDL remains in the blood to scum up arteries without it
why does the lower synthesis of cholesterol within cell inhibits HMG-CoA reductase?
stimulates storage of cholesterol as esters –> activates acyl CoA: cholesterol acyltransferase (ACAT), which decreases syntheis sof LDL protein receptors and the amount of mRNA encoding those receptors, which is why dietary cholesterol has no place to go but scum up arteries
primary risk factors in atherosclerosis
smoking 1 pack or more per day
bp diastolic >90 mmHg, systolic >105 mmHg
elevated plasma cholesterol (>240-50 mg/dL)
no correlations to ahterosclerosis?
plants, fish, veg fat, veggies
describe hyperlipidemia 2b and 4
2b – elevated LDL, VLDL, cholesterol and triglycerides and low LDL receptor
4 – elevated vldl, normal or high triglycerides and cholesterol and high VLDL
name anatomy of blood vessel
intima is innermost layer, media is smooth muscle cells, adventitia is separated from adventitia by inner elastic membrane
blood endothelial cells intima internal elastic membrane media adventia
2 key events of cvd
endothelial injury and foam cell formation in the intima region
name the enodthelial injury during heart disease
ldl breakage of endothelial layer triggers inflammatory response, releasing free radicals that oxidize the LDL and more plaque forms
what is a macrophage?
specialized white blood cell that ingests foreign particles and infectious organisms and can become stuck in the tear of artery wall
special bc universal soldier, does not require memory of foreign molecules, regardless of what it is, engulfs it and enzymatically chews it up
adventitia separated from media (smooth muscle cells) by what?
inner elastic membrane
four cell types present to oxidize ldl
smooth muscle cells
macrophages
enodthelial cells
monocytes
what happens in accumulation of foam cells?
buildup expands the intima into the lumen of the arteriole, which restricts blood flow
HDL amplifies what?
inflammatory reactions in cardiovascular risk
what is a vaccination?
administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease
what kind of micro-organisms is HIV?
retrovirus
what is immunity?
mechanism used by the body as protection against environmental agents that are foreign to the body
what is innate immunity (nonspecific immune system)?
physiological barriers, phagocytosis, dendritic cell, natural killer cells, macrophages, biologically active substances
provide chemical and physical barrier
identify and remove xenobiotic
activate adaptive immune system
activation of antibody complexes
acquired immunity?
learned immunity, adaptive immunity, t and b cells
What is an antigen?
a substance that reacts with antibody molecules and antigen receptors on lymphocytes. An immunogen is an antigen that is recognized by the body as nonself and stimulates an adaptive immune response.
recognition mechanisms of innate immunity
rapid response in hours
invariant
limited number of specificities
constant during response
adaptive immune system is specific how?
highly specialized immune system, specific antibodies and response, designed for robust and rapid removal of foreign cell,
DEVELOPS IMMUNE MEMORY
explain b cell triggers
b cell triggered when it encounters a matching antigen, engulfing the antigen. The b cell then displays antigen fragments bound to its unique mhc molecules. combo of antigen + major histocompatability complex attracts the help of mature matching T cell to secrete cytokines. The B cell multiplies and mature into antibody producing plasma cells released into the blood to lock onto matching antigens. It is then cleared by the complement cascade or by liver.
when T cells come to the aid of a b cell displaying antigen fragments, what are the two types of T cells it can become?
helper t – attract fresh macrophages and neutrophils and other cytokines to direct the recruits when they arrive onscene
cytotoxic – track down cells infected with virus and induce DEATH
recognition mechanisms of adaptive immunity
slow response (Days to weeks) variable numerous highly selective specificities improve during response
routes of transmission
sexual
contaminated needles
breastmilk
from mom to baby at birth
how does hiv reduce levels of CD4 T cells though three main mechanisms?
direct viral killing of infectd cells
increased rates of apoptosis in infected cells
killing infected CD4+ T cells by cytotoxic lymphocytes that recognize infected cells
HIV infects immune system but treatment with antiretroviral drugs reduce what
mortality and morbidity of HIV infection
when CD4 + T cell numbers decline below a critical level, cell-meditated immunity is lost, and the body becomes what?
more susceptible to opportunistic infections
body relationship of immune response to amount of virus is direct or inverse?
inverse
how does hiv avoid the immune system?
CD8 t cell kill virally infected CD 4 helper T cells
CD4 t tells with virus die via apoptosis easily
HIV can directly kill the cell
what does treatment do for HIV?
hidden virus in tissues but treatment is effective
what do fusion inhibitors do?
block HIV from fusing with a cell’s membrane
what do protease inhibitors do?
interfere with hiv protease enzyme, which breaks hiv protein chain into parts
what do integrase inhibitors do?
interfere with his integrase enzyme so it cannot be incorporated into DNA
waht is severe weight loss due to hiv and aids called
wasting, as much as 5% loss increase mortality and morbidity, tends to be lean tissue, increased energy expenditure
lipodystrophy
fat distribution change
