Unit 6 - Cellular energetics Flashcards
how do living organisms comply with the 2nd law of thermodynamics?
law states that in every spontaneous RXN, will increase entropy
- life must disorder surroundings more than it disorders self
- 1 visible E –> ~80 IR
what makes ATP’s phosphoric acid anhydride bonds “energy rich”?
the 2 phosphoanhydride bonds are so E-rich b/c:
- charge repulses are relieved upon breaking alpha-beta or beta-gamma bonds
- greater resonance stabilization of products (ADP + Pi or AMP + PPi)
- more favorable interactions with products of water
the phosphoester bond from alpha PO3 to adenosine is not as high E
how are fuels “burned” in controlled steps to extract E in usable form and amount? (energy flow)
electrons on photosynthetic pigments are raiesd to an E level where they can reduce CO2
- E required is provided by absorption of visible photons
- E stored in reduced fuels is converted to ATP by multiple enzyme-controlled steps
- ATP drives work function, returning E to environment as heat (IR photons)
- life disorders its surroundings more than it orders itself by disordering light energy (2nd law thermodynamics)
what 3 work functions do our cells need to perform to stay alive?
mechanical work, transport work, and biosynthetic work
-ATP directly drives all mechanical, and directly/indirectly drives transport and biosynthetic
how is energy storage a 3 tier system?
immediate E needs = ATP
intermediate term = glycogen
long term = fats, PRO
what is the usual flux of ATP in mammals?
turnover is 1 minute
-humans have 2 oz of ATP at any given time, thus go throguh 100 lbs/day
why is ATP well suited for its role as E carrier?
- number of phosphates (b/c sometimes ADP isn’t enough; also ensures RXN can go to completion)
- soluble and mobile (go from exogonic RXN to endergonic RXN)
- high affinity binding to enzymes
- recognition handle
why are ATP’s phosphoric acid anhydride bonds well suited for a role in E transfer?
kinetic stability VS thermodynamic instability
- without an enzyme, requires a lot of activation energy (very few molecules can supply this)
- whether there is an enzyme or not, will give off -7.3 kcal/mol of energy (delta G’)
- an intermediate thermodynamic value is consistent w/ ATPs role as an acceptor and donor of E
how is ATP an acceptor and donor of energy?
ATP accepts P from high energy phosphate compounds
-phosphoenolpyruvate
-1,3-bisphosphoglycerate
-phosphocreatine
ATP donates P to low E phosphate compounds
-glucose-6-phosphate
-glycerol-3-phosphate
how do enzymes employ the common intermediate principle to couple E-releasing RXNs to E-requiring RXNs?
if X –> Y needs -10.3 kcal/mol, and ADP + Pi –> ATP + H20 gives off + 7.3 kcal/mol…
X + E –> EX + Pi –> EP + Y needs -1 kcal/mol
-the “missing” 9.3 kcal/mol is in the EP
ADP + EP –> E + ATP needs -2 kcal/mol
total delta G’ is not altered (always equals 3)
in this case, EP is the common intermediate
how can there be channeling of ~P via NTPs?
exergonic reactions create ATP, which have interconversions via NDK to make…
- UTP –> polysaccharides
- CTP –> lipids
- GTP –> proteins
- all NTPs –> RNAs
- dNTPs –> DNA
what are the advantages of having a central pool of E in the body?
due to nucleoside diphosphatase kinase (NDK), NTP pools can share available energy and avoid rate-limiting steps (like if you flee a predator)
-GTP + ADP GDP + ATP has a free energy change of zero b/c breaking 1 bond and making another
how can levels of ATP, ADP, AMP, and Pi reflect the energy state?
regulatory enzymes have evolved regulatory binding sites that can sense the energy state of the cell by binding adenine nucleotides
- ATP generating pathways are inhibited by high levels of ATP, and stimulated by ADP/AMP
- regulatory enzyme that turns a pathway on/off in response to the E state of the cell usually catalyze an early step of the pathway (feedback inhibition)
how are ATP levels maintained short-term under stressful conditions?
- phosphagens
- in vertebrate muscle and nerves (creatine kinase)
- -phosphocreatine + ADP creatine + ATP - adenylate kinase (ubiquitous)
- 2 ADP ATP + AMP - adenylate deaminase (liver and skeletal muscle)
- AMP + H2O – AD –> IMP + NH3
- -by removing AMP, the AK RXN is pulled forward
what molecule is at a central branch linking numerous pathways?
glucose 6 phosphate (first step is converting glucose to G6P with hexokinase + ATP)
why is glucose-6-phosphate trapped in cells?
there is no transporter for G6P as opposed to glucose
why does liver use glucokinase instead of hexokinase?
liver exports glucose when blood glucose is low, and hexokinase is very aggressive (binds glucose tightly)
-glucokinase is less aggressive (affinity for glucose is 500 fold weaker) so can release it when needed
what does phopshoglucose isomerase do? why?
glucose 6 phosphate to fructose 6 phosphate
-sets the stage for an aldol cleavage between C3/4 (needs carbonyl at C2) to give two equal 3-C fragments after phosphorylation of C1 hydroxyl
what does phosphofructokinase do?
with Mg++ and ATP, transfers gamma phosphoryl of ATP to newly freed C1 hydroxyl of F6P
-plays central role in regulation of glycolysis
how is alcoholic fermentation done?
pyruvate + NADH –> NAD+ + CO2 + ethanol
-not reversible
how is homolactic fermentation done?
pyruvate + NADH NAD+ + lactate
- LDH is readily reversible
- hydride transfer to C2 carbon of pyruvate, with protonation of resulting hydroxyl O2
how does fructose enter glycolysis in muscle?
fructose + ATP + hexokinase –> fructose-6-phosphate
how does fructose enter glycolysis in liver?
fructose + ATP + fructokinase –> fructose-1-phosphate + fructose-1-phosphate aldolase –> glyceraldehyde + ATP + glyceraldehyde kinase –> glyceraldehyde-3-phosphate (GAP)
how does mannose enter glycolysis?
mannose + ATP + hexokinase –> mannose-6-phosphate + phosphomannose isomerase –> fructose-6-phosphate
-requires aldose/ketose isomerization
what does a deficiency in galactokinase result in?
galactitol formation, which causes cataracts
-reduced from aldose to alcohol
what does a deficiency in UMP transferase cause?
mental retardation and liver failure b/c buildup of UDP-glucose
-treat by screening newborns and removing lactose from diet
which enzyme catalyzes, any cofactors, and type of enzyme:
glucose + ATP glucose-6-P + ADP
hexokinase or glucokinase (liver only)
-phosphorylation that needs ATP
which enzyme catalyzes, any cofactors, and type of enzyme:
glucose-6-P fructose-6-P
phosphoglucose isomerase (isomerization)
which enzyme catalyzes, any cofactors, and type of enzyme:
fructose-6-P fructose-1,6-bisphosphate
phosphofructokinase
-phosphorylation that needs ATP
which enzyme catalyzes, any cofactors, and type of enzyme:
fructose-1,6-bisphosphate DHAP + GAP
aldolase (dihydroxyacetone + glyceraldehyde-3-phosphate)
-aldol cleavage
which enzyme catalyzes, any cofactors, and type of enzyme:
DHAP GAP
triose-P isomerase
-isomerization
which enzyme catalyzes, any cofactors, and type of enzyme:
GAP + Pi + NAD+ 1,3-bisophosphoglycerate + NADH
GAPDH (glyceraldehyde-3-phosphate dehydrogenase)
- requires NAD+ and acyl thioster
- both oxidation and phosphorylation
which enzyme catalyzes, any cofactors, and type of enzyme:
1,3-bisophosphoglycerate + ADP 3-phosphoglycerate + ATP
phosphoglycerate kinase
-requires ADP for substrate-level phopshorylation
which enzyme catalyzes, any cofactors, and type of enzyme:
3-phosphoglycerate 2-phosphoglycerate
phosphoglycerate mutase
-needs P-his for intramolecular phosphoryl transfer
which enzyme catalyzes, any cofactors, and type of enzyme:
2-phosphoglycerate phosphoenolpyruvate
enolase
-dehydration reaction
which enzyme catalyzes, any cofactors, and type of enzyme:
phopshoenolpyruvate + ADP pyruvate + ATP
pyruvate kinase
-needs ADP for substrate-level phosphorylation
which enzyme catalyzes, any cofactors, and type of enzyme:
glucose-6-P glucose-1-P
phosphoglucomutase
-needs P-serine for intramolecular phosphoryl transfer
which enzyme catalyzes, any cofactors, and type of enzyme:
glucose-1-P + UTP UDP-glucose + PPi
UDP-glucose (phosphoanhydride exchange), pyrophosphorylase/pyrophosphatase (hydrolysis)
-needs UTP
which enzyme catalyzes, any cofactors, and type of enzyme:
UDP-glucose + glycogen –> UDP + glycogen+1
glycogen synthase
-needs UDP for glucosyl transfer
which enzyme catalyzes, any cofactors, and type of enzyme:
7-residue fragment linked 1-4 glucosyl + Pi –> glucose-1-P
branching enzyme
-transglycosylation
which enzyme catalyzes, any cofactors, and type of enzyme:
terminal 1-4 linked glucosyl + Pi –> glucose-1-P
glycogen phosphorylase
-phosphorolysis
which enzyme catalyzes, any cofactors, and type of enzyme:
trisaccharide from 4-residue branch to another branch
debranching enzyme
-transglycosylation
which enzyme catalyzes, any cofactors, and type of enzyme:
cleavage of single 1-6 linked glucosyl –> glucose
debranching enzyme
-hydrolysis
what causes Von Gierke disease?
- what is the organ affected?
- how does glycogen in affected organ change?
- what are clinical features?
defective glucose-6-phosphatase or transport system
- affects liver and kidney
- increased amounts of glycogen, but normal structure
- massive enlargement of liver
- -failure to thrive
- -severe hypoglycemia, ketosis, hyperuricemia, hyperlipidemia
what causes Anderson disease?
- what is the organ affected?
- how does glycogen in affected organ change?
- what are clinical features?
defective branching enzyme (alpha-1,4 –> alpha-1,6); only liver polymers; makes Abs against it
- affects liver and spleen
- normal amount of glycogen, but very long outer branches
- progressive cirrhosis of liver
- -liver failure causes death before 2 years
what causes McArdle disease?
- what is the organ affected?
- how does glycogen in affected organ change?
- what are clinical features?
defective phosphorylase
- affects muscle (doesn’t break glycogen down)
- moderately increased amt of glycogen, normal structure
- limited ability to perform strenous exercise b/c painful muscle cramps
- -otherwise, pt is normal and well developed
