Oxygen friend of foe Flashcards
what was the first life sustaining process
photosynthesis
cyanobacteria
first element in the world
nitrogen
what to cyanobacteria do
fix Co2 dissolved in the water and release oxygen
how many times is anaerobic inefficient compared to aerobic
16
porto-bacteria ( oxygen using) got swallowed by bigger cells and used them as specialised intracellular breathing compartments. The bacteria then become what
mitochondria - these then grow into eukaryotic cells
how much O2 in atmosphere
21%
colourless odourless and tasteless
covalent bond results from the filling of molecular orbitals of each atom
can oxygen react with smoke
yes
functions of ATP
substances across cell membrane
muscle contraction ( chromosome and flagella)
energy for cells
atp made of what
adenine and ribose bound to 3 phosphate groups through phosphate ester bond and 2 high energy phosphoanhydride bonds
Atp bond lose how much energy
30.6kj/mol
which organ uses the most energy
liver - blood glucose -27%
Brian second with 19%
neurones -80% of this - synapse
what is the BMR
basal metabolic rate - rate of energy expenditure per unit time by endothermic animals at rest. Define as the Total energy conversion rate of a person at rest. - not active
how much energy is lost by BMR
exercise
thermogenesis/digestion of food
respectively
70
20
10%
redox reaction
transfer of oxygen between two species
reducing agent
supplies electrons
oxidation agent
accepts electrons
oxidation
removal of electron
Fe2+ –> Fe3+ + e-
reduction
addition of e-
Fe3+ + e- –> Fe2+
respiration is
the process of breaking down organic molecules to harvest chemical energy
glucose completely oxidised
what disaccharides is glucose broken down from
sucrose and lactose
What family of glucose transporters are used in mammals
GLUT/SLC2A
mostly GLUT1 - two conformational states - glucose binding site faces the outside of the membrane , in the other a glucose binding site faces the inside
Two types of electron carriers that are both derived from vitamin D that are important in respiration
NAD+- nicotinamide adenine dinucleotide
FAD- flavin adenine dinucleotide
Reduced forms of electron carriers are NADH and FADH2 are produced when
glycolysis, pyruvate oxidation and citric acid cycle
Glucose can relatively easily and can be converted to what in the cytoplasm of cells
glucose-6-Phosphate
what is the pathway that coverts glucose-6-Phosphate into glycogen ( glycogen is a glucose reserve for blood and muscles, most stored in liver and muscle tissues)
glycogenesis
when the body needs glucose a process know as what breaks down glycogen into glucose
glycogenesis
via what pathway does glucose-6 phosphate form ribose ( essential for nucleic acid synthesis as well as some fatty acids )
pentose phosphate pathway
glucose-6-phophate Is converted to what 3 carbon molecule
pyruvate
38ATP total
Generation of most of the energy occurs in the mitochondria membrane from acetyl CoA in the electron transport chain. Also when we get to this stage we produce citrate which go on to the production of what
fatty acids
4 main stages of respiration
glycolysis
link reaction
Krebs cycle
oxidative phosphorylation
in the process of lactic acid fermentation pyruvate is converted to lactase by what enzyme
lactase dehydrogenase
lactate goes to the liver to undergo gluconeogenesis - what is this?
production of new glucose from non-carbohydrate carbon substances such as lactate and glycerol and glycogenic aa
when does lactic acidosis occur
in the presence of inadequate tissue perfusion , abnormalities in carb metabolism and with the use of certain medications
Serum lactate levels can be both a marker for risk as well as a therapeutic target.
where does glycolysis take place in a cell
cytoplasm
where does Krebs cycle occur
mitochondrial matrix
where does the link reaction take place
mitochondrial matrix
in the link stage what happens
pyruvate I converted and oxidised into Acetyl CoA - pyruvate oxidations , electrons transferred and CO2 formed
for each glucose molecule at the stage of Krebs what haas been made NADH FADHs ATP CO2
8 NADH
2 FADH2
2 ATP
6 CO2
1 turn of Krebs cycle produces what
3 NADH
1 GTP
1 FADH2
2CO2
I glucose molecule through the link stage produces what
2 NADH
2CO2
what happens to oxygen in the electron transport chain
electrons reduced oxygen producing water
and electro from NADH and FADH2 are passed to protein complexes iin the electron transport chain
accepted by oxygen at terminal acceptor and combines with two hydrogen to form water
chemiosomosis
movement of ions across a selectively permeable membrane - down their electrochemical gradient
used to generate 90% of ATP made during aerobic glucose catabolism
during chemiosmosis electron carriers like NADH and FADH donate electrons to electron transport chain what change to shapes of protein to pump hydrogen ions acrosss selectively permeable membrane
conformational
uneven distribution of Ions established electrochemical gradient
if opened they would tend to go back to matrix driven by electrochemical gradient - can’t due to non polar regions of phospholipid bilayer
what membrane protein allows hydrogen ions to move through membrane
ATP synthase - tiny generator down their electrochemical gradient - adds phosphate to ADP to make ATP
ATP falls to a value of 5-10% - life threatening
what is the name of process of chemiosmosis that produces ATP in mitochondria called
oxidative phosphorylation
how many ATP does glycolysis produce
4 but only 2 net as 2 used up
how many ate made in link
0
how many ATP Ade in Krebs
2
how many ATP made in oxidative phosphorylation
34
what is the best electron transporter molecule because it can carry more ions
and where do the respective electron trasporters work
NAD+- used in liver
FAD+ - brain
what are intermediates can be made during respiration
amino acids
other sugars and lipids
there are numerous genetic disease that stem from enzymes deficiencies in the glycolytic pathway
a deficiency in hexokinase type 1 causes what
haemolytic anemia ( red blood cell destroyed faster than can be made)
Hexokinase II is a leading enzyme and glucose ‘sensor’ in insulin-sensitive tissues, and a defect causes what
type 2 diabetes
Glucokinase is also a glucose sensor, and low-activity and low-stability mutants can explain in part the
maturity-onset diabetes of the young (MODY).
tarui disease
different amino acid substitutions of the muscle phophofructokinase causes an exertion myopathy and haemolytic syndrome
phosphofructokinase deficiency
how many subunits does the neixyme phosphofructokinase have
3
PFKL (liver),
PFKM (muscle), and PFKP (platelet). The combination of these subunits varies depending on the tissue in
question.
In this condition, a deficiency of the M subunit (PFKM) of the phosphofructokinase enzyme impairs the
ability of cells such as erythrocytes and skeletal muscle cells to use carbohydrates (such as glucose) for
energy. Unlike most other glycogen storage diseases, it directly affects glycolysis.
The mutation impairs the ability of phosphofructokinase to phosphorylate fructose-6-phosphate prior to its
cleavage into glyceraldehyde-3-phosphate which is the rate limiting step in the glycolysis pathway.
Inhibition of this step prevents the formation of adenosine triphosphate (ATP) from adenosine
diphosphate (ADP), which results in a lack of available energy for muscles during heavy exercise. This
results in the muscle cramping and pain that are common symptoms of the disease.
Fumarase deficiency (or fumaric aciduria) is an exceedingly rare autosomal recessive metabolic disorder characterized by a deficiency of the enzyme fumarate hydratase.
occurs in what cycle
krebs
affects nervous systems
Sx - small head size ( microcephaly), abnormal brain structure, severe developmental delay , weak muscle tone and failure to gain weight and grow
seizures
could have unusual facial features - forehead, ears, jaw
enlarged liver and spleen and excess red blood cells of deficiency of WBC
hardly live
what kind of disease involve the dysfunction of the oxidative phosphorylation OXPHOS
mitochondrial diseases
what is Huntington’s disease characterised by
chorea
psychiatric disturbances
demnetia
pathologically by loss of long projection neurones in the cortex and striatum
decreased activation of electron transport chains 2 and 3
what is the venous P02 and PCO2
PO2 = 100mmHg and PCO2=40mmHg
pressure of oxygen dissolved in the blood and how well oxygen is able to move from airspaces of lungs and blood
the systemic tissue PCO2=45mmHG
what does this do
pressure gradient drives CO2 out of tissue cell into capillaries so blood returning to the lungs is that and PO2= 40mmHg
what does oxygen cascade mean
progressive decrease in the partial pressure of oxygen from the ambient air to the cellular level
when does Po2 reach its lowest level
in the mitochondria 10-20mmHg
hypoxia
low oxygen - defined as deficiency in the amount of oxygen that reaches the tissues of the body
two types
acute or chronic
generalised hypoxia - whole body
specific organ - tissue hypoxia
hypoxemia
inadequate amount of oxygen travelling in the blood
what are the 4 types of hypoxia
hypoxic hypoxia
anaemic hypoxia
circulatory hypoxia
histotoxic hypoxia
what is hypoxic hypoxia
what is a symptom
PO2 is below normal either due to alveolar PO2 reduced ( envrionemtnal - due to altitude) or cannot equilibrate fully with alveolar air ( emphysema or fibrosis)
cyanosis - appearance of blue or purple coloration of the skin or mucous membranes due to tissues near the skin surface having low oxygen saturation
what is anaemic hypoxia
lungs are in perfect condition
oxygen caring capacity of blood is reduced
CO produces this - bind to Hb with such affinity - tissues don’t get sufficient need to maintain metabolic need
Circulatory hypoxia
lungs are fine and blood can carry sufficient oxygen
tissue is not receiving sufficient 02 as heart cannot pump blood to the tissue
e.g. sickle cell anaemia lead to this as the cell sickle block blood vessels
Histotoxic hypoxia
cells have been poisoned
no problem getting O2 to tissues - lungs, blood and circulatory system all fine
the tissue is unable to use the oxygen
e.g. cyanide lead to this poisons system - cell thereof experience lack of O2 and are affected as if there was little/no oxygen available
cyanosis
blue skin or mucous due to tissues near skin having low O2 saturation
what is the first response of the body to hypoxia
goes into anaerobic respiration
loss of oxidative phosphorylation and decreased generation of ATP
The depletion of ATP results in failure of the sodium pumps, with loss of potassium, influx of sodium and
water, and cell swelling. There is progressive loss of glycolgen and decreased protein synthesis.
the depletion of ATP pumps results in failure of what
failure of the sodium pumps, with loss of potassium, influx of sodium and
water, and cell swelling. There is progressive loss of glycolgen and decreased protein synthesis.
when the cell swells as extra fluid builds up in the cell what happens to the cell
distended and cellular organelles appear to become
more spaced out within the cell. More importantly, most of the extra fluid actually builds within the
endoplasmic reticulum, causing the ER to appear much more distended. As time goes on, regions of the ER
burst and become encapsulated in clear vacuoles containing chunks of the ER. This is known as vacuole
degeneration.
what ion plays a crucial role in cell death
calcium ions
a free radical
species capable of independent existence that contains one or more unpaired electrons
very unstable and highly reactive
reactive oxygen species
collective term that includes oxygen radicals and certain non-radicals that are oxidising agents or/and easily converted into radicals
in other words all oxygen radials are ROS but not all ROS are oxygen radicals
define oxidative stress
‘a disturbance in the pro-oxidant – antioxidant balance in favour of
the former, leading to potential damage’
The effects of oxidative stress depend upon the size of these changes, with a cell being able to overcome
small alteration and regain its original state. However, more severe oxidative stress can cause cell death,
and even moderate oxidation can trigger apoptosis, while more intense stresses may cause necrosis.
what is a superoxide
anionic form of molecular oxygen - cytotoxic and biologically toxic
what ROS is released during respiratory burst
hydrogen peroxide - only bacteriacidal or cytotoxic at very high concentrations and can pass through cell membranes
how are hydroxyl radicals generated
haber-weiss reaction and Fenton reaction with iron
Mitochondrial ROS (mtROS or mROS) are reactive oxygen species (ROS) that are produced by
mitochondria. Generation of mitochondrial ROS mainly takes place at the electron transport chain located
on the inner mitochondrial membrane during what process
oxidative phosphorylation.
leakage electrons at what complex of the electron transport chain leads to partial reduction of oxygen to from superoxide
comple 1 and 3
Collectively, both superoxide and
hydrogen peroxide generated in this process are considered as mitochondrial ROS.
what intracellular compartments are capable of ROS generation
(endogenous sources)
Intracellular compartments including mitochondria, the endoplasmic reticulum, peroxisomes,
nuclei, the cytosol, plasma membranes, and even extracellular spaces
what is the major site of ROS production in most mammalian cells
mitochondrial electron transport chain
exogenous sources of ROS
pollutants, radicals, smoke, food, drugs , heavy metals
which base is the most susceptible to oxidative changes and why
guanine
lower reduction potential and hydroxyl radicals interact with the imidazole ring of this
nitrogen base at positions C4, C5 and C8.
The most studied marker for DNA oxidation is 8-
hydroxydeoxyguanosine, a product of guanosine oxidation by HO•
. This product is able to pair with
adenine, generating a GC/TA mutation upon replication.
what are the 2 forms lipid per oxidation occurs
one enzymatically, involving the
participation of cyclooxygenase and lipoxygenase in the oxidation of fatty acids and other nonenzyme
mediated, involving transition metal, reactive oxygen species and reactive nitrogen species
excess periodisation results are very damaging to the cell despite contribute to the inflammatory response , due to its importance of prostaglandin formation The action of free radicals on lipids leads to the formation of
lipid hydroperoxides and aldehydes that contribute further to increased cellular toxicity and can be
detected in biological samples to measure what
oxidative stress
the effects of oxidation in proteins is observed in impaired in?
impaired protein folding
side chain and backbone fragmentation
cysteines and methionines
leukaemia
blood cancer
the genes that code for the positive cell cycle regulators are called
proto-oncogenes
when proto-oncogenes are mutated what do they become
oncogenes ( genes that cause a cell to become cancerous )
what are tumour suppressor genes
segments of DNA that code for negative regulator proteins - when activated these can prevent the cell from undergoing uncontrolled division
tumour suppressors are smilier to brakes in a car if they fail you crash
mutated p53 genes play what normal role at which checkpoint
G1 checkpoint - cell with this mutation fail to detect errors in DNA - or be Abel to signal repair enzymes - either apoptosis or cancer
the human body is equipped with what to counterbalance the effect of ROS
antioxidants e.g. SAD,CAT and GPx
these E act by control or prevent formation of free radicals or ROS
Since superoxide is the primary ROS produced from a variety of sources, its dismutation by SOD is of
primary importance for each cell.
there are different types such as SOD1,2 and 3
where are they all found
SOD1- cytoplasm of cells and some in inter-membrane space of mitochondria ( CU,Zn)
2- manganese one, mitochondrial matrix and produced in cytoplasm
3- tissues on the extracellular matrix on cell surfaces
what does catalase do
catalyses the decomposition of hydrogen peroxide to water and oxygen. Catalase
has one of the highest turnover numbers of all enzymes
what is respiratory burst ( sometimes called oxidative burst)
rapid release of ROS ( superoxide radical and hydrogen peroxide) from different types of cells - usually fm immune cells such as neutrophils and monocytes
Respiratory burst plays an important role in the immune system. It is a crucial reaction that occurs in
phagocytes to degrade internalized particles and bacteria. To combat infections, immune cells use NADPH
oxidase to reduce O2 to oxygen free radical and then H2O2.
Neutrophils and monocytes utilize myeloperoxidase to further combine H2O2 with Cl−
to produce
hypochlorite, which plays a role in destroying bacteria.
absence of what molecule will prevent the formation of ROS and will result in chronic granulomatous disease
NADPH oxidase
hyperbaric oxygen therapy HBO is what
exposure of a patient to a partial pressure of oxygen greater than oee atmosphere - 5% more
10 to 15 times more oxygen
A high partial pressure of oxygen in capillary blood provides a larger gradient for the diffusion of oxygen
from blood to tissues. This is especially useful in tissues rendered hypoxic by microvascular angiopathies
such as in diabetes and radiation necrosis.
true or false
true
does the increased oxygen from HBO enhance the ability of white blood cells to kill bacteria , reduces swelling and allows new blood vessels to grow more rapidly into the affected areas.
yes It
does this in multiple ways, including acting as a bactericidal agent particular to anaerobic pathogens and
increases fibroblast and collagen production.
Photodynamic therapy is a sophisticated and highly selective way to ablate tissue.
There are a number of applications of PDT
what are they
Non-melanoma skin cancers Lung cancers Bladder cancers Gynaecological cancers Brain tumours Acne Age related macular degeneration Warts
There are three main components in PDT these include a photosensitiser (a drug sensitive to light), tissue
oxygen and light. The combination of these three cause the destruction of cells by reactive oxygen species.
