EXAM 1 Flashcards
what are the four functions of metabolism
- obtain free energy for the cell
- degrade macromolecules as required for biological function
- convert nutrients into macromolecules
- assemble macromolecules into cellular structures
T/F metabolism does not require tightly coordinated cellular activity
F, it does require
T/F living organisms need a continuous influx of energy to battle entropy
T
what is known as the sum of all of the chemical reactions occuring in the cell
Metabolism
define metabolism
the overall processes by which living things acquire and utilize free energy in the cell
what are the basic units of metabolism
enzymes
substrates of the enzymes of metabolism are called
metabolites
define metabolic pathway
a series of connected enzymatic reactions that produces a specific product
T/F metabolic pathways consist of sequential steps
T
two compartments of metabolism
catabolism and anabolism
define catabolism
degradative pathways the produce free energy
define anabolism
biosynthetic pathways that consume free energy
In a catabolic pathway the electrons energy-yielding nutrients lost are stored in…
NADH
FADH2
NADPH
List the energy-yielding nutrients that are used in catabolism
Cabrohydrates
Fats
Proteins
In an anabolic pathway, where do you get the energy you need to proceed the reaction
NADPH
List the cell macromolecules of anabolic pathways
Proteins
Polysaccharides
Lipids
Nucleic Acids
List the precursor molecules in anabolic pathway
Amino Acids
Sugars
Fatty Acids
Nitrogenous bases
ATP hydrolysis is important for
biosynthesis
osmotic work
cell motility/muscle contraction
Energy-requiring cellular activities are powered by ATP hydrolysis, liberating what as products
ADP and Pi
In energy requiring cellular activities are powered by
ATP hydrolysis
Why is ATP a high energy compound?
hydrolysis increased resonance stabilization which allows for shifting of bonds
hydrolysis decreased electrostatic interactions
hydrolysis increased energy of solvation/entropy
what is the reaction that occurs between NAD+ and NADH ?
dehydrogenase reaction
what is the most common e- carrier that always transfer two e- at a time
NADH
What is NADH used in? What about NADPH?
NADH used in fuel metabolism , mobile e- carrier for ETC/PMF/ATP synthesis, catabolism
NADPH used for biosynthesis, anabolism
Compartmentalization
Metabolic pathways are localized within different cellular compartments/locations
T/F anabolic and catabolic pathways involving same product are not the same
T
T/F some steps may be common to both anabolic and catabolic pathways
T
what ensures that each pathway is spontaneous/thermodynamically favorable
unique enzymes
define biosynthetic enzymes
operate as part of anabolic pathways
define degradative enzymes
operate as part of catabolic pathway
water-solube vitamins almost always ……
converted to coenzymes
T/F Fat soluble vitamins are stored for longer periods of time
T
how are metabolic pathways controlled?
Thermodynamics
compartmentalization
metabolic flux
how can metabolic flux be controled
allosteric
covalent modification
substrate cycles
genetic control
T/F ATP does not need to be biosynthesized
F, it must be biosynthesized
ATP/equivalent molecules are used to….
power endergonic processes
glycolysis is divided into 2 phases what are they
investment phase
payoff phase
define glycogen
multi-branched polysaccharide of glucose
where does glycogen fit into metabolic picture
degraded when glucose is needed ( low energy status)
synthesized for energy storage ( high energy status)
define glycolysis
pathway for glucose breakdown that consists of 10 enzymes that make end product pyruvate
define PPP
alternative pathways that allows for NADPH production and provides biosynthetic precursors
define GNG
pathway in liver and kidneys that allows for the production of glucose from pyruvate, lactate and amino acids
where does glycolysis occur
in cytoplasm
T/F glycolysis is anaerobic
T
the first phase of glycolysis converts glucose to
2 glyceraldehyde-3-phosphate at the expense of 2 ATP
second phase of glycolysis produces
2 pyruvate
2 ATP YIELD
2 NADH
List all substrate and enzymes along with biproducts in glycolysis in order
- Glucose
ATP -> ADP || Hexokinase/glucokinase
2. Glucose 6 Phosphate
|| Phosphoglucoisomerase
3. Fructose 6 Phosphate
ATP –> ADP || Phosphofructokinase
4. Fructose - 1,6 - bisphosphate
|| aldolase
- Dihydroxyacetone phosphate + Glyceraldehyde 3 phosphate
( Triose phosphate isomerase)
NAD+ –> NADH||Glyceraldehyde-3-Phosphate DH
- 1,3- Bisphosphoglycerate
ATP –> ADP || Phosphoglycerate kinase
- 3 phosphoglycerate
|| Phosphoglycerate mutase
- 2-phosphoglycerate
release H2O || enolase
- phosphoenol pyruvate
ADP –> ATP || pyruvate kinase
- Pyruvate
lactate DH function
reduces pyruvate to lactate using NADH
reversible
cori cycle
TPP defecincy causes
beriberi disease
symptoms of TPP deficiency
Pain
Paralysis
wasting
heart failure
pyruvate decarboxylase requires
thiamine pyrophosphate (TPP)
the making of glucose from non-carbohydrate precursor is what pathways
GNG
GNG meets body’s glucose needs under
fasting conditions
GLUT 2
low affinity transporter in hepatocytes (liver) and pancreatic cells
GLUT 4
higher affinity transporter in adipose tissue and muscle cells
why is it important for GLUT 4 to have higher affinity for glucose than GLUT 2
liver is able to make its own glucose so we want to give other cells such as the muscle and adipose tissue to have first dibs to get the sugar they need
what glucose transporter serves as sensor for insulin release
GLUT 2
compare and contrast GLUT 2 and GLUT 4 in terms of Km and kinetics
GLUT 4 has a low Km and 0th order kinetics
GLUT 2 has high Km and 1st order kinetics
how does insulin promote glucose entry into cells
allows for increased production of GLUT4 through vesicle fusion
T/F glycolysis does not use oxidative phosphorylation it is a substrate level phosphorylation reaction
T
what is the enzyme used for the priming reaction in glycolysis
hexokinase/glucokinase
compare hexokinase and glucokinase
HK
- present in muscle and most tissues
- low Km
GK
- present in the liver and pancrea ( b-islet cells)
how is Hexokinase regulated
inhibited by high levels of glucose-6-phosphate
Insulin activates
glucagon inhibits
how is glucokinase hormonally regulated
induced by insulin in liver
why do we have two different enzymes (HK/GK) for the conversion of glucose to G6P?
it makes sure that all other cells like muscles can get what they need and THEN the liver will deal with the leftover glucose and store it
what are other fates of glucose-6-phosphate other than glycolysis ?
- PPP to make NADPH
- Glycogen
- carbohydrate synthesis
describe the mechanism of HK and GK
glucose does nucleophilic attack in P group of ATP causing an induced fit releasing ADP and leaving a P group attached
what enzyme forms glucose-6-phosphate from glucose
HK/GK
Phosphoglucose isomerase function
reconfigures bonds to form F6P
T/F Phosphoglucose isomerase has a small value of free energy change indicating that the reaction is near equilibrium and is therefore a regulated step
F, it is reversible enzyme due to the small value in free energy change
why does the reaction of phosphoglucosisomerase occur
- b/c next step is a second phosphorylation and a hemiacetal is a tougher reaction compared to Primary -OH
- puts carbonyl at C2 which activates C3 for an aldolytic cleavage
what enzymes of glycolysis has an enediol intermediate
Phosphoglucoisomerase
Triose Phosphate Isomerase
what kind of reaction is PGI
acid-base catalysis
what are the irreversible enzymes of glycolysis
GK/HK
PFK1
Pyruvate Kinase
what is the enzyme known as the first committed step of glycolysis
PFK1
How is PFK1 regulated
High levels of AMP activate it
High levels of ATP and Citrate inhibit
when will we see PFK activity increase and decrease
increase: lw energy status
decrease: high energy status
how is PFK allosterically regulated
Fructose-2,6-bisphosphate and AMP : activates PFK1
citrate and atp inhibit
How is PFK1 hormonally regulated
High levels of insulin = activate
High levels of glucagon = inhibit
how does insulin activate PFK1
it activates PFK2 which converts F6P to F26BP , a potent allosteric activator, which in turn activates PFK1
How does glucagon inhibit PFK1
glucagon inhibits PFK2, and stimulates F26BPase of GNG inhibiting PFK1
function of aldolase in glycolysis
cleavage step, beaks F16BP into 2 3C units, DHAP and GA3P
There are 2 classes of aldolase enzymes, compare the two types
Class I Aldolase:
- found in animal tissues
- formation of covalent Schiff-Base E-S intermediate
Class II Aldolase:
- contain. an active site metal (ZN2+) to help shield the oxyanion intermediate
function of Triose Phosphate Isomerase
undergoes isomerization reaction that is reversible interconvert b/w DHAP and GA3P
what type of chemistry is utilize in TPI
acid base
in TPI mechanism what amino acids function as general bases and acids
Histidine
Glutamate
function of glyceraldehyde 3 phosphate DH
catalyzes oxidation and addition of Pi group to GA3P forming 1,3BPG and producing NADH
what enzyme of glycolysis uses NAD+ as a cosubstrate that involves exchange of electrons
glyceraldehyde 3 P DH
characteristics of the mechanism of GA3PDH
covalent catalysis ( thioester bond formed)
nicotinamide enzyme
oxidative
T/F GA3PDH usess cystein residue to form thioester bond
T
function of phosphoglycerate kinase
transfers a P group from 1,3BPG to ADP to make ATP and form 3- Phosphoglycerate
what enzymes of glycolysis are referred to as substrate level phosphorylation
Pyruvate Kinase
Phosphoglycerate Kinase
define mutase
an enzyme that catalyzes the migration of a function group within the substrate molecules
What is a detour of 1,3BPG other than going straight to 3-PG that is seen in RBC
forms 2,3BPG via 1,3BPG mutase and then forms 3-PG via 2,3BPG phosphatase
function of 2,3BPG
regulators of Hemoglobin decreasing affinity for O2 which aids in O2 release ( R–> T state) in RBC
function of Phosphoglycerate mutase
catalyzes a phosphoryl group transfer from C3 to C2 forming 2-phosphoglycerate
what enzymes requires Mg2+ for enzymatic activity
phosphoglycerate mutase
enolase
what enzyme utilizes a phosphohistidyl residue
Phosphoglycerate mutase
function of enolase
a dehydration reaction ( loss of H2O)
forms phosphoenolpyruvate
function of pyruvate kinase
uses PEP as a phosphate group donor to release ATP forming pyruvate
How is Pyruvate Kinase Regulate
activated by high levels of AMP & F16BP
inhibited by high levels of ATP and acetyl-CoA
function of lactate dehydrogenase
reversible enzyme that can oxidize NADH to NAD+ ( reduce NAD+ to NADH)
Cori Cycle
function of DHAP other than glycolysis
used in liver and adipose tissue for TAG synthesis
what are the high energy intermediates of glycolysis used to generate ATP by substrate level phosphorylation
1,3BPG
PEP
what are the three fates of pyruvate
- TCA cycle
- Fermentation (yeast)
- Lactate ( in animals)
what are the steps from pyruvate to form ethanol in yeast fermentation
- pyruvate decarboxylase
- alcohol DH
Pyruvate Decarboxylase characteristics
requires TPP
T/F high levels of lactate in muscles cause pain
T
where does galactose enter to glycolysis and how many enzymes are used
enters as G6P via 4 enzymes
where does mannose come into the glycolysis and how many enzymes
F6P via 2 enzymes
where does fructos (muscle) come into glycolysis and name the enzyme
F6P via HK
where does fructose (liver) come into glycolysis and how many enzymes
GA3P via 7 enzymes
what pathway uses glucose catabolism to produce NADPH
PPP
where does glucose synthesis occur
liver and kidneys in animals
list out all the steps in GNG include enzymes and biproducts and substrates
- Pyruvate
CO2 + ATP –> ADP|| Pyruvate Carboxylase - OAA
GTP–>CO2 + GDP||PEP carboxykinase
- PEP
enolase - 2PG
PGM - 3PG
ATP –> ADP || PGK - 1,3-BPG
NADH –> NAD+ || GA3PDH - GA3P <— TPI —> DHAP
aldolase
- F16BP
H2O || Fructose bisphosphatase
- F6P
PGI
- G6P
H2O || G6Pase
Glucose
list the important substrates for GNG
Pyruvate
Glycerol 3 P
Lactate
Alanine/ Gluconeogenic AA
what are the irreversible enzymes of GNG
Pyruvate Carboxylase
PEP Carboxy Kinase
Fructose 1,6 Bisphosphatase
Glucose 6 - Phosphatase
What is the only enzyme of GNG found in the mitochondria
Pyruvate carboxylase
what is cofactor required for the mechanism of pyruvate carboxylase and its function
biotin
serves as a mobile CO2 carrier
how is pyruvate carboxylase regulated
high levels of acetyl CoA activate
high levels of AMP inhibit
glucagon and cortisol activate
describe the mechanism of pyruvate carboxylase
uses ATP to load CO2 onto biotin and then delivers it to pyruvate
T/F biotin contains a lys residue
T
what is unique about PEP carboxykinase mechanism
uses GTP rather than ATP for energy
why in GNG does cell add CO2 with pyruvate carboxylase and then take it back off with PEPCK?
decarboxylation drives the formation of enol that GTP phosphorylates
function of PEP carboxykinase
converts OAA to PEP
via GTP and decarboxylation
how is PEPCK regulated
activated by high levels of glucagon and cortisol
how is fructose 1,6 bisphosphatase regulated include hormonal
high levels of citrate and ATP activate
high levels of AMP and F26BP inhibit
cortisol , glucagon, Epi and NE activate
function of F16BPase
removes phosphate group from F16BP producing F6P
hormonal regulation of Pyruvate carboxylase
High levels of glucagon and cortisol stimulate
what is unique about glucose-6-phosphatase
found in the smooth ER lumen
function of Glucose-6-phosphatase
converts G6P to glucose by removing a P group
T/F all cells do GNG not just the liver and kidneys
F, it is only the liver and kidney
NOTE: Muscle and brain do not do GNG
if Glucose 6Pase is in the ER lumen how is it able to release glucose into blood stream
- transporter that is concentration driven
- uses vesicles, that are filled with glucose, and fuses with plasma membrane allowing it to open and release into bloodstream
what enzyme mechanism in GNG involves nucleophilic attack by a Histidine nitrogen
Glucose 6 Phosphatase
what enzyme contains a phosphohistidine intermediate
Glucose 6 Phosphatase
draw a simple sketch of cori cycle
slide 28 of GNG
T/F PPP can occur in all cells
T
what are the two functions of PPP
make NADPH and ribose-5-phosphate (imp nor nucleotide synthesis)
name the rate limiting enzyme of PPP
Glucose-6-phosphate DH
location of PPP
cytoplasm
define oxidative phase of PPP
use glucose metabolism to help supply NADPH for reductive reactions
define nonoxidative phase of PPP
use glucose metabolism to help supply ribose-5-phosphate (essential for nucleotide synthesis )
list the steps of the oxidative phase of PPP
- G6P
NADP > NADPH || glucose-6-phosphate DH
- 6phosphogluconolactone
H2O || 6Phosphogluconolactonase
- 6 phosphogluconate
NADP > NADPH + CO2 || 6Phosphogluconate DH
- Ribulose 5 Phosphate
what phase of PPP is irreversible and when is it operating
oxidative phase
on when cells need to make NADPH
when will PPP be turned on
highhhh ATP levels
functions of NADPH
biosynthetic metabolite for FA and cholesterol (electron donor )
protects against ROS ( acting as body natural antioxidant)
Glucose - 6- Phosphate DH regulation
High levels of NADPH inhibits
High levels of NADP+ activates
what metabolite is hydrolytically unstable and readily undergoes spontaneous ring opening hydrolysis
6-phosphogluconolactone
what enzyme of PPP serves to to accelerate the spontaneous ring opening via hydrolysis
6-phosphogluconolactonase
why is it important for the spontaneous ring opening in PPP to be accelerated by phosphogluconolactonase
to prevent accumulation of toxic molecule 6-phosphogluconolactone
what makes the mechanism of 6-phosphogluconate DH unique
has 2 phase
- NADP+ dehydrogenation
- decarboxylation event
function of phosphopentose isomerase
converts ketose to aldose
function of phosphopentose epimerase
changes orientation of OH group at C3 changing stereochemistry
Transketolase function
transfer of 2 carbon units
TPP dependent
transaldolase function
transfers a 3-C unit
Schiffs base mechanism
describe the function of Mode 1 of PPP
undergo oxidative phase because Ribose5P and NADPH is needed
describe function of Mode 2 of PPP
nonoxidative phase from glycolytic intermediates to produce only Ribose 5 P because it is need and No NADPH is needed
describe function of MODE 3 of PPP
NADPH is needed but no R5P
undergoes oxidative phase to produce NADPH and R5P
but since R5P is not needed it will feed into GNG so that it can continued to make NADPH
describe function of MODE 4 of PPP
ATP is needed and NADPH is needed
will undergo oxidative phase and R5P produced feeds into glycolysis at F6P , GA3P, and DHAP
define glycogen
multi-branch polysaccharide of glucose
stores glucose
where does glycogenolysis and glycogenesis occr
skeletal muscle and liver
what organ/tissue has a higher concentration of glycogen reservoir
Liver
why does the liver have higher concentration of glycogen stored
it has a role to maintain blood glucose levels at 5mM
what are the pros of having branch points in Glycogen
more efficient storage
allows for activity to move
define starch
a-linked chains of glucose in plants
amylase function and location
found in saliva
hydrolyzes a1–>4 glycosidic bonds of starch
STARCH debranching enzyme a(1–>6) glucosidase function
hydrolyzes 1 glucose residuce at a time
targets a(1–>6) bonds
STARCH debranching enzyme oligo (a1,4 –> a1,4)glucanotransferase function
takes a1->4 and moves it to another branch point
a-glucosidase function
hydrolyzes 1 glucose at a time
SOLE enzyme capable of a(1>6) glycosidic bonds
what enzyme leaves glycogen with one less branch point
a-glucosidase
function of glycogen phosphorylase
allows for breakdown of a(1.4) glycosidic bonds forming glucose-1-phosphate
regulation of glycogen phosphorylase in muscles
activated by high levels of AMP and Epi
inhibited by High levels of ATP & G6P
regulation of glycogen phosphorylase in liver
activated by glucagon
function of phosphoglucomutase
converts G1P to G6P
what enzyme is shared between glycogenolysis and Galactose metabolism
Phosphoglucomutase
function of glycogen synthase
forms a1,4 glycosidic bonds on linear glucose
how is glycogen synthase regulated
activated by insulin and high levels of G6P & ATP
inhibited by glucagon and Epi via protein kinase cascade (PKA)
function of UDP-glucose pyrophosphate
forms ester linkage b/w C1-OH and B-Phosphate of UDP activating glucose moiety of UDP glucose
what enzyme of glycogenesis occurs via an oxonium ion intermediate
glycogen synthase
amylo-(1,4 -> 1,6) transglycosylase function
cuts at a1,4 bond and moves it to C6 of glucose molecule forming an a1,6 glycosidic bond
why is glycogen metabolism linked to G1P and not G6P
G1P cant escape the cell and gives cells time to determine what is needed conversion
separates point of flux for controlling whether glycogen is synthesized or broken down
glucagon and Epi activate a cascade of reactions that stimulate what and inhibit what ( terms of glycogen)
glycogen breakdown
inhibit glycogen synthesis
