biochem exam 1 part II Flashcards
glucose
the major fuel for most organisms
if totally oxidized, delta G = -2840 kJ/mol
versatile precursor: from it, can synthesize C=skseltons of most major molecules
fates in higher plants & animals:
- stored (polysaccharides, sucrose)
- oxidized to a 3-C compound (pyruvate): glycolysis
- oxidized to pentoses
fates of glucose
storage
- can be stored in polymeric form (starch, glycogen)
- when there’s plenty of excess energy
- glycogen, starch, sucrose
oxidation via glycolysis
- generates energy via the oxidation of glucose
- short-term energy needs
- pyruvate
oxidation via pentose phosphate pathway
- biosynthesis of lipids and nucleotides
- generates NADPH via oxidation of glucose
- ribose 5-phosphate
synthesis of structural polymerase
- cell walls of bacteria and plants
- ECM & cell wall of polysaccahrides
glycolysis
the almost-universal central pathway for carbohydrate catabolism (breakdown)
results in the storage of energy n atp and NADH
the first part of the catabolism of glucose, either anaerobic (fermentation - alcoholic or lactic acid) or aerobic
A 2-phase process
phase 1: preparatory (investment) phase
- glucose is phosphorylated and cleaved to form 1 molecule of glyceraldehyde3-phosphate. 2 ATP molecules are invested
phase 2- payoff phase
- 2 glyceraldehyde 3-phosphates are converted to 2 pyruvates. The payoff of 4 ATP and 2 NADH molecules
another representation:
energy investment phase:
2 ATP + glucose -> 2 ADP
energy payoff phase
4 ADP -> 4 ATP
2 NAD+ -> 2 NADH (reduction, step 6)
net:
glucose -> 2 pyruvate + 2 H2O
2ADP + 2Pi -> 2atp
2 NAD+ -> 2 NADH + 2H+
Fates of Pyruvate (More Later)
Aerobic Conditions: pyruvate is oxidized to yield the acetyl group of acetyl-coenzyme A.
That acetyl group is then oxidized completely to CO2 by the citric acid cycle
Pyruvate→Acetate→CO2 + H2O
NADH + O2 + 2H+ → NAD+ + H2O
Anaerobic Conditions:
Animals and microbes convert pyruvate into lactate when O2 is lacking
Through transforming pyruvate into lactate, NADH is oxidized to replenish NAD+
Replenishing NAD+ allows glycolysis (ATP production) to continue for a short time
Summary of Glycolysis and Energetics
how much of the energy in glucose is removed through glycolysis?
C6H12O6 (glucose) + 6O2 -> 6CO2 + 6H2O
delta G = -2840 kJ/mol
Glc + 2 NAD+ -> 2 pyruvate + 2 NADH + 2H+
delta G = -146 kJ/mol
146/2840 = 5.2%
much energy remains in pyruvate
Summary of Glycolysis and Energetics
glc + 2 NAD+ + 2 ADP + 2Pi
-> 2 PYRUVATE + 2NADH + 2H+ + 2ATP + 2H2O
glycolysis is very exergonic:
delta G = -85 kJ/mol
you can also think about glycolysis as a 2part process
Glc + 2 NAD+ ->. 2pyruvate + 2NADH + 2H+
delta G = -146 kJ/mol
2 ADP + 2Pi -> 2ATP + 2H2O
delta G = +61 kJ/mol
(-146 + 61 = -85 kJ/mol)
this shows that 146 kJ/mol are removed from glucose and 61 kJ/mol are stored as ATP
Summary of Glycolysis and Energetics
Glc + 2ATP + 2NAD+ 4ADP + 2Pi -> 2pyruvate + 2ADP + 2NADH + 2H+ +4ATP + 2H2O
or the net rxn:
Glc + 2NAD+ 2ADP + 2Pi -> 2 pyruvate + 2 ATP + 2 H2O
used:
1 glucose
2 ATP
2 NAD+
made:
2 pyruvate - various different fates
4 ATP - used for energy requiring processes within the cell
2 NADH - a high energy molecule, must be reoxidized to NAD+ in order for glycolysis
Glycolysis
1- 5: “preparatory phase”
Phase 1: - Preparatory (Investment) Phase Glucose is phosphorylated and cleaved to form 2 molecules of glyceraldehyde-3-phosphate. Two ATP molecules invested
Glycolysis: Step 1
Glucose-6-phosphate is produced
from blood glucose by hexokinase
Glucose phosphorylated at C-6
It keeps glucose in the cell!! because the phosphate is negatively charged and cannot pass through the phospholipid bilayer.
Glucose is now Charged - due to a negative charge from phosphate
Exergonic → irreversible
delta G = -16.7 kJ/mol
Uses/stores energy of ATP. First ATP invested! (other ATP investment is step 3 I think)
Hexokinase allosterically regulated by glucose-6-phosphate
Mg2+ lowers activation energy
(Ch #6 Biochem I – Enzyme Mechs)
1 - exergonic
2 - energy stored in the phosphate bond
3- regulated, steps 1,3,10
4 - induced fit
Glycolysis: Step 2
Isomerase converts glucose-6- phosphate to fructose-6- phosphate
6-membered ring to 5
Reversible (small ∆G) of 1.7 kJ/mol
Mg2+ lowers activation energy (Ch #6 Biochem I – Enzyme Mechs)
Glycolysis: Step 3
Fructose-6-phosphate is phosphorylated by phosphofructokinase-1 (PFK-1)
Fructose phosphorylated at C-1 Symmetrical☺now, 1,6-biphos.
Keeps all later products in the cell!! Charged.
Exergonic → irreversible Uses/stores energy of ATP
Second ATP invested!
Mg2+ lowers activation energy
(Ch #6 Biochem I – Enzyme Mechs)
1 - exergonic
2 - energy stored
3- regulated, steps 1,3,10
4 - induced fit
Glycolysis: Step 4
Fructose-1,6-bisphosphate is cleaved into two, 3-C molecules by aldolase:
- Glyceraldehyde-3-phosphate (G-3-P) ☺
- Dihydroxyacetone phosphate (DHAP) Gotta change this!
1 -> 2 molecules: endergonic, but coupled to later rxns
- FROM HERE ON, EACH REACTION IS HAPPENING TWICE! (except Step 5 – ha!)
Glycolysis: Step 5
Dihydroxyacetone phosphate (DHAP) from Step 4 is converted to Glyceraldehyde-3-phosphate (G-3-P)☺ through triose phosphate isomerase
Now we have two G-3-Ps from 1 glucose!
Prep. Phase Done!
Glycolysis
6 - 10: payoff phase
Phase 2: - Payoff Phase
2 molecules of glyceraldehyde- 3-phosphate are converted to two molecules of pyruvate.
Four ATP molecules and 2 NADH molecules were produced.
Glycolysis: Step 6
Glyceraldehyde 3-phosphate is phosphorylated/oxidized to 1,3-bisphosphoglycerate
NAD+ is reduced to NADH
1,3-Bisphosphoglycerate has a phosphate group we can cleave, and release energy to drive reactions (remember reaction coupling?). Also storing energy in the NADH.
G3P is oxidized and NAD+ is reduced (a redox rxn!!!)
NAD+ is reduced to NADH
Glycolysis: Step 7
ATP is synthesized (2 ATPs come back→net = zero at this point) as phosphoglycerate kinase transfers the phosphate group from 1,3-Bisphosphoglycerate to ADP
1,3-Bisphosphoglycerate → 3-Phosphoglycerate + ATP
Energy released used to pull previous rxns 4, 5 & 6
Glycolysis: Step 8
3-Phosphoglycerate → 2-Phosphoglycerate Just moving a phosphate group around
isomerization, small delta G
Glycolysis: Step 9
2-Phosphoglycerate doesn’t have a lot of energy compared to other compounds:
Phosphoenolpyruvate
So let’s convert 2-phosphoglycerate to Phosphoenolpyruvate (PEP) via enolase
Dehydration has a small deltaG
Glycolysis: Step 10
Phosphoenolpyruvate →Pyruvate + ATP
Via pyruvate kinase
Here is where we gain 2 ATP and now net two ATP.
THIS IS THE PAYOFF!
Irreversible
Note the Mg2+
Vry exergonic hydrolysis of PEP coupled to ATP formation stores energy and drives the whole process; allosterically regulated
allosterically Activated by: AMP and fructose-1,6-biphosphate
Allosterically Inhibited by: ATP and acetyl-CoA
summary of glycolysis and energetics
Glc + 2 ATP + 2 NAD+ 4 ADP + 2 Pi
–> 2 Pyruvate + 2 ADP + 2 NADH + 2 H+ 4 ATP + 2 H2O
or the net rxn:
*Glc + 2 NAD+ 2 ADP + 2 Pi
—> 2 pyruvate + 2 NADH + 2 H+ 2 ATP + 2 H2O
used:
1 glucose
2 atp
2 nad+
made:
2 pyruvate - various different fates
4 ATP - used ro energy-requiring processes within the cell
2 NADH - a high energy molecule, must be reoxidized to NAD+ for glycolysis to continue
Which of the steps of glycolysis is/are regulated?
A
1, 3
B
1, 3, 7, 10
C
1, 3, 10
D
7, 10
C
1, 3, 10
7 & 10 have ATP coming out
1 & 3 have ATP going in
Glycolysis and Cancer
in most tumors, there is limited O2 availability ( hypoxia) and therefore less aerobic metabolism
for ATP production, cells become more dependent on glycolysis. Glucose uptake increases and glycolysis is accelerated
one type of chemotherapy targets glycolysis
so since there is not a lot of O2, the tumor uses glycolysis to get its energy
Other Pathways Can Lead to the Glycolysis Pathway
Multiple feeder pathways exist for glycolysis:
- Glucose cleaved from glycogen and starch (polysaccharides) to give glucose-1- phosphate
- Dietary disaccharides and polysaccharides are hydrolyzed
getting sugars to feed into glycolysis
KNOW: that not all sugars are glucose and need to have different pathways to get different sugars to enter into glycolysis
Polysaccharide Feed-in to Glycolysis
how glycogen enters glycolysis
non-reducing ends at the glycogen units
glycogen phosphorylase cuts off the non-reducing ends into glucose 1 phosphate
then made into glucose 1 phos.
glucose 1 phos. + isomerse = G6P and can enter into glycolysis
starch + amylase in mouth
= maltose + dextrins to make glucose
glucose + hexokinase = G6P and can enter glycolysis
Disaccharide Feed-in to Glycolysis
maltose + maltase = 2 glucose
*lactose + lactase = glucose + galactose
sucrose + sucrase = glucose + fructose*
trehalose + trehalase = 2 glucose
Monosaccharide Feed-in to Glycolysis
in liver:
fructose –> glyceraldehyde 3 phos.
muscle & kidney
fructose –> fructose 6 phos.
mannose –> fructose 6 phos.
primarily in the liver
galactose –> G1P –> G6P
Fates of Pyruvate
Aerobic Conditions: pyruvate is oxidized to yield the acetyl group of acetyl-coenzyme A.
That acetyl group is then oxidized completely to CO2 by the citric acid cycle
Pyruvate→Acetate→CO2 + H2O
NADH + O2 + 2H+ → NAD+ + H2O
Anaerobic Conditions:
Animals and microbes convert pyruvate into lactate when O2 is lacking
Through transforming pyruvate into lactate, NADH is oxidized to replenish NAD+
Replenishing NAD+ allows glycolysis (ATP production) to continue for a short time
anaerobic metabolism: pyruvate to lactate in human muscle cells
pyruvate + lactate dehydrogenase + NADH + H+ –> NAD+ + Lactate
during vigorous exercise, lactate accumulate in muscle tissue, eventually causing pain and possibly limiting exercise capability
anaerobic metabolism: pyruvate to ethanol in yeast
in yeast and some other organisms
thiamine pyrophosphate (TPP) a coenzyme derived from thiamine is often required for decarboxylation rxns when the carboxyl group is adjacent to carbonyl group
pyruvate —> acetaldehyde —> ethanol + CO2 + NADH to NAD
Under anaerobic conditions in human muscle cells, pyruvate is metabolized to…
A
Acetyl-CoA
B
Ethanol
C
Lactate
D
PEP
E
TPP
C
Lactate
IN YEAST it is ethanol
from catabolism (breakdown) to anabolism (synthesis)
we just did catabolism
now we will go over anabolism
glycolysis (catabolism) is related to gluconeogenesis (anabolism)
catabolism:
- we have 3 carb. molecules
- make ATP, NAD(P)H, precursors
anabolism
- use ATP, NAD(P)H, precursors to make carbs and various other molecules
Carbohydrate Biosynthesis
anabolism going on
plants
- CO2 + light = starch and sucrose photosynthesis
animals
- take catabolic products (pyruvate, lactate) and make them into anabolic products
organizing principles of biosynthesis
- antiparallel pathways: may share some reversible rxns with catabolic pathways, but there is usually 1 irreversible unique to each way - at steps 1, 3, 10
- regulation: at least 1 - coordinate reciprocal - usually early in the chain
- rxns usually coupled to ATP hydrolysis (exergonic) to make the process irreversible
Our Body Needs Glucose…all the time, constantly,…
the brain, nervous system, erythrocytes, testes, renal medulla, and embryo tissues, are completely or majorly dependent upon glucose for fue
the body carriers only a little more than a 1 day’s supply of glucose
what if glucose stores run out
if glucose is not obtained in the diet, the body must produce new glucose from noncarbohydrate precursors
central pathway from precursor to carbohydrates: gluconeogenesis the system for glucose
anabolic
occurs in almost all organisms
in animals, for the cells of many organs (especially the brain) glucose is the major or sole energy source
in higher animals, primarily in the liver
main precurosrs: pyruvate , lactate
and/or: oxaloacetate, glucogenic amino acids
glycolysis:
- start with glucose
- end with pyruvate
gluconeogenesis
- start with pyruvate
- end with glucose
Glycolysis and Gluconeogenesis
7 common enzymes
3 rxns of glycolysis are so exergonic that they are irreversible:
- step 1: hexokinase
- step 3: phosphofructokinase-1 (PFK-1)
- step 10: pyruvate kinase
gluconeogenesis ‘detours’ around these
Gluconeogenesis is not the reverse of glycolysis
The three exergonic and highly regulated reactions in glycolysis are
replaced by alternative reactions in the gluconeogenic pathway.
The results of these reactions are similar intermediates
glycolysis and gluconeogenesis
7 & 10 rxns are shared
bypasses for the 3 very exergonic (~irreversible) rxns
Gluconeogenesis Step 1: (Bypass of Glycolysis Step 10)
Antiparallel to Glycolysis Step 10.
- Glycolysis: PEP → Pyruvate
- Gluconeo. Pyruvate→oxaloacetate→PEP
- Complex and costly (1 ATP + 1 GTP), need to put energy into bonds to build something new
- Exergonic(because of the above)
- NADH consumed in mitochondria, reformed in the cytosol
- What do you think stimulates/inhibits these enzymes?
Consider what we are doing…
glucose to pyruvate and o2 was around so we went to the citric acid cycle
Gluconeogenesis Step 1: (Bypass of Glycolysis Step 10)
biotin: cofactor involved in CO2 transfer
CO2 + pyruvate –> oxaolocateose + phosphate
costs energy, uses GTP
biocarbonate + pyruvate …
when pyruvate is available
bypass #1a: a complex process
oxaloacetate cannot go through mitochondria so it needs to be turned into malate then converted back into PEP
pyruvate from cytosol goes into mitochondria
pyruvate turns into OA
OA to malate
malate in mitochondria goes to the cytosol
malate to OA
OA to PEP
Bypass #1 rxns
summary:
pyruvate to OA
OA to malate
malate to PEP
not finished yet…
also when lactate is available (usually inn muscle cells) then it can turn into pyruvate, which can turn into OA, malate, back to OA then to PEP
Also NADPH determines the fate of G6P whether it goes to PPP to make amino acids and nucleotides or glycolysis to be broken down into pyruvate for storage for when we need to make more glucose
