vert phys exam 1 Flashcards
acclimatization example
at high altitude with low pO2, more BPG and RBCs to carry oxygen
positive feedback ex
blood clotting;
blood vessel injury releases chemicals that activate platelets and cause coagulation
activated platelets release more chemicals and attract more platelets to injury site
autocrine regulation
chem. regulators affect same cells as produce them
physiology
study of functioning organisms and how organisms function
structure determines function, following laws of chem and phys
EC fluid - interstitial =
plasma volume
plasma vol + EC fluid =
interstitial fluid volume
plasma vol + EC fluid =
interstitial fluid vol
homeostatic mechanisms EX
shivering
epithelial cell function
- form boundary between compartments
- selectively permeable to ions and organic molecules
- basolateral surf rests on basement membrane
steady state value that body maintains
set point
set point
steady state value that body maintains
location of internal pacemaker that sets biological rhythms
suprachiasmatic nucleus of the brain
suprachiasmatic nucleus of the brain
location of internal pacemaker that sets biological rhythms
endocrine control EX
heart rate increases from epinephrine release by adrenal medulla into bloodstream
4 cell types
epithelial, nerve, muscle, connective-tissue
homeostatic variable
in steady state of DYNAMIC CONSTANCY that is regulated to remain near a stable set point value
feed forward regulation
smell of bad food triggers the gag reflex
Smell/odor receptors trigger response in digestive sys
prepare stomach for arrival of food before it comes
saliva, churning, produce acid
steady state EX
upon entering a hot room, begins sweating
continued sweating keeps body temp stable
ID the EFFECTORS -
eating salt-rich meal increases blood volume and pressure, stretching vessel walls
nerve signals sent to brainstem stimulate Changes in hormonal/neural signaling.
heart rate slowed, blood vessel walls relax, kidneys increase salt exerted in urine
BP returns to normal
heart, blood vessels, kidney
ligand
molecule/ion that binds protein
A solution containing proteins of a particular type is exposed to the same concentrations of ligands X and Y, but the percent saturation of molecule X is greater than the percent saturation of molecule Y. why?
soon protein has a higher affinity for ligand X
increase temp of chem rxn
increase forward and reverse run rate
products of glycolysis under anaerobic conds
2 ATP, 2 H2O, 2 lactate
krebs cycle
generates ATP directly by substrate level phosphorylation
RDS in metabolic path
slowest reaction, subject to end-product inhibition
true of fatty acid synthesis
begins with acetyl coenzyme A (coA)
occurs in cytosol
requires more energy than is produced by catabolism of same fatty acid
results in even # of carbon atoms only
\enzymes that synthesize fatty acids are found separately from enzymes that catabolize
muscle cell types
skeletal, cardiac, smooth
connective tissue cells
form ECM (fibers and collagen)
tissues
aggregates of differentiated cells with same type
body fluid compartments
intracellular fluid 67%
plasma: part of blood which cells are suspended
interstitial
EC fluid
interstitial fluid and plasma
why is there homogeneous solute composition in EC fluid?
EC fluid = interstitial + plasma
Because of exchanges, concentrations of dissolved substances are identical in the plasma and interstitial fluid, EXCEPT for protein concentration (higher in plasma)
Compartmentalization
achieved by barriers
- plasma membranes surround each cell, separate the intracellular from the extracellular fluid
- 2 components of extracellular fluid— interstitial fluid and plasma—are separated by blood vessel walls.
homeostasis
- state of dynamic constancy
- stability of variable achieved by balancing input and output (not magnitudes)
- Traits fluctuate within a predictable and often narrow range. 4. When disturbed out of normal range, restored to normal.
- dynamic process regulates adaptive responses of body to changes in environ
- require sensor to detect environ change
- require compensatory mechs
- achieved by expenditure of energy
compensatory mechanisms
restore homeostasis/set point
body temp as control sys EX
- person at norm temp into cold
- person loses heat to ext. enviro bc cold outside
- compensation: chem rxns produce heat at rate = rate heat loss
- blood vessel narrow and restricted, reducing blood flowing thru skin, decreasing heat loss from warm blood across skin into environ
- body undergoes no net change and remains about constant;
steady state
- control sys operates around set point; maintainence
steady state
system where a variable is not changing but in which heat/energy must be added continuously to maintain stable, homeostatic condition
NOT equilibrium (no input of energy req’d to maintain constant)
ALL homeostatic control sys operate around a set point
negative feedback
thermoregulation
a change in variable being regulated brings response that moves opposite the initial change towards the original point.
corrective resp. after steady state perturbed
Negative feedback EX
product formed from substrate –> product reaction by an enzyme negatively feeds back to inhibit further action by enzyme (ATCase; ATP)
as ATP accumulates, it inhibits the activity of enzyme and production slows down
resetting set points
FEVER;
set point for body temp has been set higher and body responds by shivering to generate heat
feedforward regulation
improves the speed of body homeostatic response and minimizes fluctuations of regulated variable (reduces variation from set point) using environmental detectors/learning
CHANGES IN REGULATED VARIABLES ARE ANTICIPATED/PREPARED FOR BEFORE THEY OCCUR
changes in regulated variable are anticipated/prepared for before they can occur
improves speed of homeostatic response
feedforward regulation
feedforward regulation of temp
temp-sens neurons in skin monitor temp outside
when its cold out, neurons detect change and relay info to brain which signals blood vessels/muscles resulting n heat conservation and increased heat production
COMPENSATORY thermoregulation is ACTIVATED BEFORE colder outside temps can cause a decrease in internal boy temp
reflexes (control sys)
specific involuntary built-in response to stimulus
can be automatic or learned/acquired from practice
specific involuntary built-in response to stimulus
can be automatic or learned/acquired from practice
reflex
reflex arc mediation
stimulus acts on receptor and produces signal to be relayed to integrating center. signal travels along AFFERENT pathway to integrating center
output is sent to EFFECTOR which acts along efferent pathway
- if effector response causes decrease in stimulus trigger, then reflex leads to negative feedback and typical homeostatic control
stimulus
detectable change in environ
local homeostatic responses
initiated by change in environment/stimulUs, induce alteration of activity with NET EFFECT OF COUNTERACTING STIMULUS
stimulus/change in environment causes change in activity met by response with net effect of counteracting the stimulus
local homeostatic response
- result from stimulus
- local area resp.
- nor nerves/hormones directly involved
hormones
chem. messenger that communicate and use the blood as a delivery sys for target
NTs
chem messengers released from neurons ending on other cells and diffuse thru EC FLUID separating neuron from its target
NOT released into blood like hormone
paracrine
local communication between neighbor cells
- NTS
adaptation
characteristic that favors survival in specific environments
- homeostatic control systems are inherited and allow individuals to adapt to environ changes
acclimatization
prolonged exposure to environmental change = improved functioning of already existing homeostatic system
reversible
adaptation/acclimatization EX
sweating in heat
day 1: expose to 30 mins of heat and make exercise. body temp increases, sweating begins
sweating is mechanism for increasing heat loss from body so body temp doesn’t rise
vol sweat measured
day7 - subject begins to sweat sooner and much more profusely than day1.
as consequence, body temp does NOT increase as much. subject ACCLIMATIZED to heat - undergone BENEFICIAL CHANGE INDUCED BY REPEATED EXPOSURE AND NOW BETTER ABLE TO RESPOND
- reversible: if exposure stops, subject reverts to preacclimatized values
sweating
adaptation allows heat loss from body to minimize an increase in body temp in hot environments
cause of acclimatization
increase in number, size or sensitivity of 1+ cell types in homeostatic control system for response to exposure
biological rhythms
add an anticipatory comp. to homeostatic control
like feedforward mechanism without detectors
allow homeostatic mechanisms to be utilized automatically by activating when a challenge is likely to occur but before it does occur
an anticipatory comp. for homeostatic control like feedforward mechanism without detectors
biological rhythm
EX of biological rhythms
- body temp increase prior to waking up so metabolic pathways can operate more efficiently
- during sleep, metabolism slower than awake so body temp decreases
cause of biological rhythm
environ factors do NOT drive rhythm but provide timing cues for entrainment (set the rhythm)
total body balance
depends on relative rates of net gain/loss to body
pool concentration depends on total amount of substance in the body and exchanges of substance within the body
total body balance depends on
- relative rates of net gain/loss
- pool concentration/total amount of substance in the body
- exchanges of substance within the body
3 states of total body balance
- loss exceeds gain: total amount substance is decreasing = negative balance
- gain exceeds loss: total amount of substance in body is increasing = Positive balance
- gain equals loss = stable balance
body balance EX
Calcium ions
conc [Ca] in EC fluid
the control system for balancing Ca targets the intestines and kidneys so amount of Ca absorbed from diet is balances with excretion
during childhood, net balance Ca is + and deposited in growing bone
later, Ca released from bones and lost in urine (rate of Ca loss exceeds intake so balance is negative)
homeostasis requires
energy to expend
compensatory mechs
sensor to detect environ change
Case study: A hot day
body temp increase, heat production decrease and heat loss increases
sweating caused EC fluid levels to decrease
eventually, fluid levels decrease so much that blood available to be pumped from heart decreased.
IF EC FLUID DECREASES, BP DECREASES.
sweat from EC fluid. more sweating and losing water (sweat is dilute EC fluid), more concentrated EC fluid is
sweat
from the EC fluid
more dilute than EC fluid bc more H2O than ions is secreted
more sweating = more concentrated EC fluid (saltier
decrease EC fluid, BP decrease
prokaryotes
bacteria,
lack membranous organelles
plasma membrane
limiting barrier, regulate passage, link adjacent cells by junctions and anchor cells to ECM
double layer of lipid molecules with embedded proteins
largest intracellular fluid comp
cytoplasm/cytosol
phospholipid bilayer
plasma membrane
amphipathic
random lateral movement of lipids and proteins bc lack of bonds
characteristic flex and fluidity
cholesterol
slightly amphipathic bc polar hydroxyl
close association limits the ordered packing of fatty acids
no cholesterol = tightly packed, less fluid
MAINTAIN IM FLUIDITY
Integral proteins
amphipathic, move laterally, associated w membrane
most are TRANSMEMBRANE
form channels
Transmembrane proteins
integral proteins
form channels
peripheral proteins
NOT amphipathic
at membrane surface, cytosolic surface and bind polar regions
assoc. w CYTOSKELETAL shape and mobility
fluid mosaic model
plasma membrane is lipid bilayer mosaic of membrane proteins that are free to move in a sea of lipids
junctions
provide barrier to movement of molecules
between cells
form tissues
integrins
transmembrane protein organizes cells into tissues by binding to ECM proteins and linking adjacent cell membranes
transmembrane protein organizes cells into tissues by binding to ECM proteins and linking adjacent cell membranes
integrin
desmosome
between 2 adj. cells
structural support and integrity
- characterized by accumulation of protein dense plaques along cytoplasmic surf of membrane
- anchoring proteins to bind cadherins of adj. cell
- bind to IM filaments
- connect w integrins
- adhesive junctions, hold adj. cells firmly together
- in areas of mechanical stress, give stability
- contains cadherins
- keratin filaments anchor
feature between 2 adj cells that provides structural support/integrity
accumulation of protein dense plaques on cytoplasmic surf
desmosome
desmosome dense plaques
anchoring proteins for cadherins
extend from 1 cell into EC space to bind w/ cadherins of adj. cell
- disk shape membrane.
in areas of mechanical stress, provide support by adhering 2 cells together in disk shape with cadherins
desmosome
tight junction everything
forms when EC surf of 2 adj. plasma membranes join together so not EC space remains between them
- adhering junctions (desmosome) must form 1st
- occurs in band around circumference of cell
- joined at apical surf
- limits movement thru EC space
- limits paracellular diffusion
- forces passage thru cells and NOT between (NO LEAKS)
- Claudin composition
- prevent epithelial mesenchymal transition
- encircle epithelial cell by connecting to actin microfilaments
- ZO-1 acts to tether cytoskeleton to transmembrane barrier protein
occurs in band around circumference of cell after an adherins/desmosome leaving so EC space between the cells
tight junctions
of epithelial cells
- at apical surf
composition includes claudin
TJ
limits movement through EC space,
limits paracellular diffusion,
prevents Epithelial mesenchymal transition
TJ force passage thru cells and not leaking between
connect to actin MFs
TJs
gap junction
protein channels linking cytosol of adjacent cells
- connexins proteins
small diam. of channel limits passage thru to small ions
protein channels linking cytosol of adjacent cells
gap junction
nucleus
Nuclear envelope contains 2 membranes with nuclear pores. RNA moves thru pores.
DNA forms w histones into chromatin (dense)
chromatin becomes chromosomes
free ribosomes
release proteins into cytosol
rough ER
proteins synthesized here pass into lumen of ER and then Golgi and secreted out
smooth ER
lipid molecules synthesized.
stores Ca2+ for muscle contractions
golgi
prots arrive from rough er and undergo mods and sorting with transport vesicles
mitochondria organelle
chem process transfer energy from bonds to ATP
most ATP formed in mitochondria BY CELLULAR RESPIRATION
- inner and outer membrane
- inner membrane folded has crustal into the matrix
cellular respiration
produces most ATP in mitochondria
consumes O2 and produces, CO2, heat water
mitochondria membranes
inner and outer
inner folds into crustal, extends into matrix
lysosomes
have acidic fluid w digestive enzymes
defense
break down
peroxisomes
consume molecular oxygen
NOT used in transfer of energy to ATP
removes H from organic molecules prods H2O2
toxic in high conc.
break down fatty acids in 2C sources which can be used for ATP
cytoskeleton
formed by protein filaments
determines cell shape, movements and contractions
- actin filaments = microfilaments (thin)
- IM
- microtubules (tubulin units)
IM filaments
assoc w desmosomes to provide support/stability
microtubules
hollow tubulin protein subunits
rigid, in neurons
radiate from centrosome
cilia core
cilia
core of microtubules
motile on epithelial cells (move mucus)
no signal sequence
synthesis continues on free ribosome and then released into cytosol, destined for function in cell/enzyme
proteome
the specific proteins expressed in a cell
protein degradation
some have high affinity for proteolytic enzymes
unfolded plots more easily digested
targeted for degradation by attachment of ubiquitin which directs the protein to a proteasome
proteasome
protein complex that unfolds and breaks down a protein
ubiquitin
regulatory protein that targets proteins for degradation by proteasome
- covalent attachment to lysine
specificity
depends on shape of binding site
ability of protein to bind active site
affinity
strength of ligand-protein binding
depends on strength and attraction between protein-ligand
with high affinity, very little ligand is required to bind
saturation
fraction of total binding sites that are occupied
% saturation depends on [unbound ligand] and affinity of binding site for the ligand
- if binding site had high affinity, low [ligand] conc. will result in high saturation bc once bound to site, ligand not easily dislodged
competition
the ability and presence of 1+ ligands to bind to same binding site affects the % of occupation
- cooperation
allosteric modulation
as shape of binding site changes, cooperation changes shape of other regions of the protein
non covalent binding of ligand to 1 site can alter the shape and binding characteristics (affinity)
active site for binding and regulatory binding site
modulators bind regulatory site
Hb EX
4 subunits for O2. when 1 O binds, affinity of other sites for O2 increase
covalent mods
often phosphate group (-) added
charge alters distribution of electrical forces and changes conformation
protein kinase mediates phosphorylation
kinase
proteins modulates phosphorylation
catalyze transfer of Pi from ATP to OH on side chain
phosphatase
dephosphorylation
metabolism
cells cannot use heat energy
synthesis and breakdown of organic molecules req’d for structure and function
generates water
reaction rate is influenced by
reactant conc.
activation energy
temperature
catalysts
active site
region of enzyme that binds substrate
cofactors
trace metals bind and work with the enzyme
can alter enzyme conformation
coenzyme
cofactor that directly participates as a substrate in a reaction. the coenzyme remains in original form throughout
derived from vitamins, NAD+, FAD
oxidized
lose electrons
loss of electrons
oxidation
gain electron
reduced
reduced
gain electrons
ATP
primary molecule that stores energy transferred from breakdown
glycolysis
carbs (glucose) only
sugar breakdown/catalysis
10 enzymatic reactions
NO Oxygen
Occur in cytosol
break down 6C glucose into 2 3C pyruvate (ionized pyruvic acid)
Net GAIN of 2 ATP, 4 H (2 released), 2 transferred NAD+
All IMs between glucose and pyruvate end prod contain ionized phosphate groups (remain trapped in cells since cannot penetrate plasma membrane)
most pyruvate is reduced to lactate
where is glycolysis
in cytoplasm, NO oxygen
1st step of (an)aerobic respiration
glycolysis in cytoplasm
glycolysis process
glucose broken down into 2 3C pyruvates. then, either lactate or to krebs cycle
pyruvate
2 3C pyruvate formed by glycolysis
mostly reduced to lactate
otherwise onto kreb’s cycle
pyruvate reduced to lactate
2 3C pyruvate of glycolysis reduced to lactate
1. 2 H atoms from NADH+ and H+ transferred to pyruvates molecules to form lactate and NAD+ is regenerated
2. remainder of pyruvate is not converted to lactate but enters kreb’s to be broken down to CO2
lactate released into blood, liver (precursor to glucose)
converted back into pyruvate, used as energy source
Kreb’s cycle
citric acid cycle forms CO2, some ATP in the inner mitochondrial matrix
pyruvate enters mitochondria from cytosol metabolized into 2C acetyl coA (release CO2)
1. primary molecule: acetyl coenzyme A coA transfers acetyl group to 4C oxaloacetate to form 6C citrate
- acetyl-CoA reacts –> generation of reduced cofactors NADH and FADH2, production of ATP thru substrate-level phosphorylation.
directly prods 1 high E NTP
Krebs cycle conditions
ONLY AEROBIC
oxidative phosphorylation is necessary for regeneration of H-free form of coenzymes
used in oxidative phosphorylation to form lots of ATP
reduced cofactors
NADH, FADH2
oxidative phosphorylation
most important mechanism for energy derivation
energy for ATP derived from energy
- mitochondria
- aerobic
E released when H ions combine with molecular O2 to form H2O
H comes from NADH, H+, FADH2 coenzymes of Kreb’s cycle, by metabolism of fatty acids
-embedded in mitochondrial membrane is ATP synthase - forms channels
coenzymes of krebs cycle
soluble in mitochondrial matrix
cytochromes
proteins contain iron heme and copper cofactors
form components of electron transport chain and transfer electrons:
- 2 e- from H are transferred … eventually to O2 to form water
potential energy of oxidative phosphorylation
hydrogen ion conc. gradient
energy of gradient converted into chemical bond by ATP synthase (catalyzes formation of ATP from ADP)
ATP synthase
embedded in mitochondrial membrane
forms channels
step forming the most ATP
oxidative phosphorylation in inner mitochondrial membrane, aerobic
occurs at inner mitochondrial membrane
krebs (cofactors) and oxidative phosphorylation (most ATP)
glycogen storage
muscles and liver
synthesis from glucose
synthesis of glycogen
add phosphate group to glucose, form glucose 6 phosphate to be broken down to pyruvate to to form glycogen
gluconeogenesis
major substrate is pyruvate formed from lactate
liver and kidneys
essential amino acids
9/20
vitamins
diff solubility
water soluble vitamins form parts of coenzymes like NAD+, FAD+, coA
hypoxia
lack of O2
Tylenol case study
cause of death was hypoxia (low O2) despite blood oxygen levels elevated
cell death and mitochondrial damage
BC
oxygen not delivered to tissues, accumulated in blood
O is final electron acceptor
stripping electrons
carbons become more oxidized for ETC
NAD+
oxidized acceptor
NADH
reduced donor
reduced
has the H
why are ppl so vulnerable to protein deficiency
no essential amino acids can be synthesized by the body, must be consumed
required for binding
concentration, orientation, and affinity
binding is random
cytochrome C oxidase
enzyme; complex 4 of ETC
transfers electrons to molecular O2 (substrate), reducing it to water
higher respiration
more water produced
law of mass action
drive rxn forward by increasing substrate. increase prods = drive backwards
when available ATP is exhausted
catabolism ensues
Km
measure of affinity
strength/tightness of ligand-protein binding
simple diffusion
no energy input besides movement from heat, NO ATP; passive
graded potentials
magnitude is related to intensity of stimulus that elicits them
magnitude is related to intensity of stimulus that elicits them
graded potential
neuronal time constant
proportional to product of membrane resistance and capacitance
proportional to product of membrane resistance and capacitance
neuronal time constant
speed of conduction of nerve impulse can be determined by
temperature and diameter of axon
If apply Na channel agonist to squid axon that is voltage clamped to -100mV…
large inward sodium current
AND
voltage gated K+ channels remain closed
EX of synaptic plasticity
- increasing amount of NT released from AP
- Increasing number of receptors on postsynaptic membrane
- altering amount of Ca entering the cell at presynaptic terminus
stimulus intensity/strength is encoded in
freq. of Pas with stronger stimuli eliciting higher frequencies
Serotonin
excitatory NT
Effect of fluoxetine in post-synaptic neuron
acts on serotonin - excitatory NT
= graded potentials of longer duration in post-synaptic neuron
oxidative phosphorylation
- ETC
- chemiosmosis
ATP synthase complex uses E released from ETC proton gradient to make ATP
electron transport chain
proteins bound to inner mitochondrial membrane; electrons pass through series of redox reactions, release energy
transfers e- from reduced molecules onto O2 to become H2O (most reduced)
as e- passed, E released and used to pump protons, create proton gradient (PE)
cellular respiration
- glycolysis in cytosol
AEROBIC, Mitochondria - krebs
- oxidative phosphorylation & ETC
net products of glycolysis
2 ATP (net), 2 H+, 2 H2O, 2 NADH, 2 pyruvate (–> lactate)
glycolysis reaction
glucose + 2 ATP + 2 NAD+ –> 2 pyruvate, 4 ATP, 2 NADH, 2 H+, 2 H2O
all IMs contain ionized phosphate group so cant permeate membrane and leave
glycolysis in cytosol
- body pH
step 4 glycolysis
fructose 1,6 - diphosphate splits into 2 molecules.
isomerase converts 1 into the other so 2 of same molecule
UNSTABLE bc 2 phosphate groups
step 1 glycolysis
glucose phosphorylated by kinase
USE 1 ATP
Mg2+ cofactor lowers Ea
step 2 glycolysis
becomes fructose
step 3 glycolysis
USE 2nd ATP w/ cofactor Mg to phosphorylate
step 5
split apart into 2. DHAP converts by isomerase into glyceraldehyde
step 6 glycolysis
2 NADH is reduced to 2 NAD+ and 2 H+
exergonic rxn releases energy to be used to phosphorylate again
step 7 glycolysis
ATP Is formed x2 from each molecule
SUBSTRATE LEVEL PHOSPHORYLATION: Pi transferred from IM substrate onto an ADP
glycolysis step 8/9
isomerize and LOOSE WATER =
PEP is unstable and looses phosphate group x2
step 10 glycolysis
unstable PEP x2 donates it phosphate group to ADP = 2 ATP
and becomes 2 pyruvate (end prod)
- go on to krebs and make CO2 or
- into lactate
end of glycolysis
if oxygen is available,
krebs and ETC breaks down pyruvate all the way into ATP
what does glycolysis NEED
2 ATP energy
carbohydrate
2 NAD+
NADH/NAD+ cycling
Oxygen:
NADH can pass its electrons into the electron transport chain, regenerating
NAD+ glycolysis.
Anaerobic: fermentation
erythrocytes
RBCs have enzymes for glycolysis but NO MITOCHONDRIA so no other pathways
lactate
prod during muscle activity
released into blood
- can be converted back into pyruvate (oxidized)
- used as precursor in liver to form glucose
use of lactate
released into bloodstream
- converted back into pyruvate
- or stored in liver as precursor to glucose
critic acid cycle facts
uses carbs, fats, and proteins to prod CO2, H atoms (half bound to coenzymes), some ATP
step 1 krebs
- Acetyl coA forms citrate
(transfer acetyl group from coA onto oxaloacetate)
pyruvate enters mitochondria from cytosol after glycolysis
metabolized into acetyl coA and CO2
NAD+ –> NADH
acetyl coA
enzyme derived from vitamin B transfer acetyl group w/ pyruvate or fatty acid breakdown
1st step of krebs
produced from OXIDATION OF PYRUVATE
krebs step 2
citrate isomerized with loss/addition of water molecule
krebs step 3
isocitrate is oxidized and releases CO2
NAD+ is reduced to NADH
krebs production of ATP
directly prods 1 high E GTP –> ATP
uses substrate level phosphorylation
How kreb’s creates ATP
substrate level phosphorylation: Pi onto GDP = GTP
GTP + ADP = ATP + GDP
creates ATP from GTP
Krebs cycle most important
H atoms transferred to reduce coenzymes and free H generated are used in oxidative phosphorylation to gen. ATP
reaction of krebs
Acetyl CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O –> 2 CO2, CoA, 3 NADH, 3H+, FADH2, GTP
why must oxidative phosphorylation/krebs be aerobic
nec. for regeneration of oxidized, H-free form of coenzymes
mitochondria CANNOT remove H from coenzymes under anaerobic conds
step 4 krebs
reduced NAD+ to NADH
release CO2
forms succinyl coA
step 5 krebs
CoA group of succinylcholine CoA is replaced by phosphate, then transferred to ADP to make ATP
= succinate
step 6 krebs
succinate oxidized.
2 H atoms are transferred to FAD = FADH2
7/8 krebs
water added, converts molecule
and malate regenerates into starting oxaloacetate
NAD+ is reduced to NADH
products of citric acid cycle
2 C enter on acetyl CoA
2 CO2 released
3 NADH
1 FADH2
1 ATP
per acetyl coA
why krebs cant operate without O2
when ET cant oxidize NADH to NAD+, there is no NAD+ available for krebs (finite)
krebs regulation
by oxygen and availability of NAD+
oxidative phosphorylation ENERGY
E transferred to ATP is derived from E released when H ions combine w/ molecular O2 to form H2O
H comes from NADH + H+ and FADH2 coenzymes generated in krebs (metabolism of fatty acids (and glycolysis))
as e= are transferred from 1 protein to another, some E released is used by cytochromes to PUMP H ions from matrix to intermemb. space = CREATES SOURCE OF PE AS H+ ION CONC. GRADIENT
oxidative phosphorylation EQ
1/2 O2 + NADH + H+ –> H2O + NAD + E
Krebs cycle enzymes
soluble in mitochondrial matrix
proteins of oxiphospho
embedded in mitochondrial membrane
1. transfer H onto molecular O2
2. couple E released to synthesis of ATP
ETC components
cytochromes (Fe and Cu cofactors) transfer H down to O2 with proteins
general ETC
2 H e- are transferred from NADH + H+ or FADH thru the chain w/ cofactor until reach O2 and form H2O
- use free H ions and coenzyme H ions
oxidized H-free coenzymes
regenerated in ETC so available to accept 2 more H from other paths
ETC regenerates H-free oxidized coenzymes NAD+ and FAD by transferring the H onto O2
rxns prod. conc gradient
flow of H+ back across membrane provides E for ATP synthase
coenzymes of krebs
oxidized in ETC so now available to accept 2 more H
H ion conc gradient
PE source of ETC
e- are transferred from 1 protein to another, releasing E to be used by cytochromes to pump the ions from the matrix into intermembrane space
ATP synthase
embedded in mitochondrial membrane enzyme that forms a channel in membrane allowing H ions to flow to matrix side
reason for channel/conc gradient in ETC
lipid bilayer blocks diffusion of ions
ATP synthase creates channel for H ions to flow to matrix side
= chemiosmosis
conc gradient of ETC Energy
E converted to chemical BOND E by ATP synthase,
catalyzes form of ATP from ADP
chemiosmosis
ATP synthase embedded in mitochondrial membrane that forms channel in membrane allowing H ions to flow to matrix side
most ATP is formed
oxidaphosphorylation from H atoms of Krebs cycle (breakdown macromolecules)
mitochondria
prods most ATP, consumes most O2, releases most CO2
entering substrate of ETC
H atoms of NADH + H+ and FADH2;
O2 formed during glycolysis and krebs
products of ETC
2-3 ATP for each NADH + H+
1-2 ATP for each FADH2
carb catabolism
breakdown carb to pyruvate or lactate by glycolysis
metabolize pyruvate to CO2 and H2O by krebs and ox phosphorylation
substrate level phosphorylation
glycolysis and krebs
net gain of 2 ATP from glycolysis
2 more ATP from krebs GTP
- 1 ATP for each of 2 pyruvate molecules entering cycle
max ATP
34 ATP
ATP production of krebs
glucose –> 2 pyruvate molecules –> 2 GTP –> 2 ATP (substrate level phosphorylation)
Anaerobic ATP production
only 2 ATP from substrate level phosphorylation in glycolysis -> lactate
energy in Anaerobic conditions
2 ATP from glycolysis
lots of glucose break down into lactate
glycogen
small amounts of glucose can be stored as reserve as polysaccharide glycogen, in liver and muscles
glycogen synthesis
from glucose
enzymes in cytosol
1. transfer phosphate from ATP to glucose
SAME 1st step as glycolysis
So, IM can be broken down to pyruvate or glycogen
glucose storage
as glycogen in liver/muscles (polysaccharides)
glycogen synthesis pathways
- catabolized to provide energy for ATP formation
- in liver cells, converted to free glucose by removal of phosphate group, then glucose can enter blood
glucose synthesis
- in liver, breakdown glycogen
gluconeogenesis
gluconeogenesis
generate new glucose from noncarbohydrate precursors
major substrate is pyruvate, formed from lactate
what determines if glucose is broken down to pyruvate or if pyruvate is used to synthesize glucose?
concentrations of glucose and pyruvate and hormones that alter/change expression
adipocyte function
synthesize and store triglycerides, release as needed for E and ATP formation
beta oxidation
coA derivative of fatty acid goes thru process which splits off acetyl coA and transfer 2 pairs of H atoms to enzymes ( 1 to FAD and 1 to NAD+)
H atoms from co enzymes then enter oxidative phosphorylation path to form ATP
ATP formed from fatty acid catabolism
18 C saturated = 146 ATP
1 glucose yields max 38 ATP
catabolism of 1g fat is 2.5x greater than 1g carb
fatty acid synthesis
- cytoplasmic acetyl coA transfers acetyl group to another and start forming chain, repetition builds up by 2C at a time
all fatty acids synthesized have even #
acetyl coA enzyme
starting material for fatty acid synthesis, Krebs cycle, formed from pyruvate
acetal coA derived from fatty acid breakdown
CANNOT be used to synth new glucose
1. pyruvate broken down into acetyl coA and CO2 is irreversible
2. the 2 C atoms in acetyl coA are used to form 2 molecules of CO2 during krebs
glucose and fatty acids
glucose can readily be metabolized to synthesize fat
fatty acids can NOT be used to synth glucose
proteases
protein catabolism break peptide bonds
macromolecules
all can enter the Krebs cycle thru some IM
all can be used as source of E for synthesis of ATP
keto acids
formed by removal of amino groups from AAs
ammonia
used to form urea in liver; excreted in urine
essential nutrients
water
(body looses more than oxphospho prods)
HILK MF TVW
water soluble vitamins
form coenzymes NAD+, FAD, coA
excreted in urine
- accumulation in body is limited
fat soluble vitamins
ADEK are not coenzymes
A - retinol
what structure contains enzyme required for oxidative phosphorylation
inner membrane of mitochondria
NOT matrix
ligand-protein binding reaction
allosteric modulation can alter affinity of protein for ligand
phosphorylation of protein is a covalent mod
if 2 ligands can bind same binding site of protein, = competition
binding reactions are electrical or hydrophobic
what can be used to synthesize glucose by glujconeogeneis in liver?
glycerol (?)
catabolism of fatty acids
2 steps
strength of ligand protein binding of binding site is
affinity
membrane structures that form channel linking together the cytosol of 2 cells and permitting movements of substances between cells
gap junction
fluid inside cells but NOT within organelles
cytosol
liquid portion of the cytoplasm, excluding the organelles
significance of folds on inner mitochondrial membrane
increases total SA
enzymes required to generate ATP are here
structure –> function
proteins and ligands relationship
protein function can be altered by allosteric changes in structure
charge attraction
energy for homeostasis
ATP provides E required for homeostatic processes
generation of ATP is under NEGATIVE feedback control.
