Fat soluble vitamins are not readily secreted but
stored in fat
What vitamins are fat soluble
vitamin A,D,E, and K
If you are lacking vitamins,
no reaction takes place
Purpose of these elements:
Mg2+:
Ca2+:
Zn2+:
-stabilize ATP
-signal transduction
-cofactor of rxns
A metabolic pathway is a series of_______reactions, often located in a specific part of the cell.
enzyme-catalyzed
Without enzymes,
reactions would be too slow for cells to survive
Enzymes provide a way to couple energetically ___________reactions with______.
-unfavorable
-favorable reactions
Catabolic reactions go through_________where it takes electrons and breaks bonds
degradation
Degradation breaks_______to_________
-complex metabolites
-simple products
Anabolism reactions go through______where_______ turn to _______
-biosynthesis
-simple products
-complex metabolites
What macromolecules are broken down in catabolism?
proteins, polysaccharides, triglycerols
The end goal of catabolism
CO2
_____is the electron carrier produced by glycolysis
NADH
Catabolism is____, and anabolism is____
oxidative, reductive
When the energy state of the cell is LOW, we would expect to see reactions taking place with end product such as?
CO2
If, in the course of a reaction, NAD+ goes to NADH, then the reaction is____
oxidative
Metabolic pathways are localized within different cellular compartments
Compartmentalization
What mechanisms occur in the cytosol?
glycolysis, PPP, fatty acid biosynthesis, many GNG reactions
What mechanisms occur in the mitochondrion?
Citric acid cycle, oxidative phosphorylation, fatty acid oxidation, amino acid breakdown, and electron transport
What are the four strategies to control enzymes?
-allosteric control
-covalent modification
-substrate cycles
-genetic control
Allosteric control includes substrates, products, and coenzymes of the pathway. This is ______feedback regulation
negative
covalent modification is a
global response
Enzymes that control flux of a pathway have specific sites that can be _______
covalently modified
Covalent modifications are_______ such as hormones
controlled by signals
In substrate cycles, the foward reaction is________while the reverse reaction is______
- accelerated
-slowed down
In genetic control, altering the concentration of enzymes can lead to
altering enzyme activity
ATP-->(ADP+Pi) doesn't have the highest free energy because
it needs time to replenish
ATP--->(ADP+Pi) has a free energy charge of_____ and needs______to make more ATP.
- -30.5 kJ/mol
- +30.5 kJ/mol
Hydrolysis increases _____ and _______
-resonance stabilization
-energy of solvation
Hydrolysis decreased_____
-electrostatic interaction

-Phosphoenolpyruvate, 1,3-bisphosphoglycerate, phosphocreatine transfer to make ATP
- ATP helps in the production of Glucose-6-phosphate and glycerol-3-phosphate
NAD+ and FAD _____electrons
accept
Reduction___electrons
gain
Oxidation___electrons
loses
Electron transfer can be
-directly as e-
-As H+ atom: 1e- transferred
-As hydride ion (H-): 2e- transferred

NADH is a common electron carrier and always transfers_____
two e-at a time
what does biosynthesis rely on?
reducing equivalents from NADH

What structure is this?
flavin(FAD)

reduced: FADH2
oxidized: FAD
Mg2+interacts with the negative charges on the phosphate group to shield negative charges,
making the molecule more stable
Pentose phosphate pathway is an alternative pathway that allows for____production and provides biosynthetic precursors
NADH
GNG is a pathway in the _____and_____ that allows for biosynthesis of glucose from pyruvate, lactate, and amino acids.
-liver
-kidney
Glycolysis and GNG are reciprocally regulated by allosteric effects, _______ and _______
-covalent modification
-changes in enzyme synthesis rates
Low affinity transporter in hepatocytes (liver) and pancreatic cells
GLUT2
Higher affinity transporter in adipose tissue and muscle cells
GLUT4
Is driven by concentration and hormones, independent of Na+
GLUT1-4
GLUT2 has about a Km=15mM and captures excess glucose primary for
Storage
GLUT2 is considered to be first order kinetics because______.
-transport is directly dependent on glucose concentration
low affinity=
fast chemistry
GLUT4 has about a Km=5mM which means transport is saturated with slightly
high blood glucose levels
GLUT4 is considered to be
zeroth order of kinetics because its constant rate.
After a meal, glucose is____.
Before a meal, glucose is______
-very high
-very low
high affinity=
slow chemistry
A stimulated cell of insulin causes for localization of _______to plasma to boost glucose uptake in cell
glucose receptors
Glycolysis occurs in the____ and doesn't require
-cytoplasm
-oxygen
The products of glycolysis are
ATP, pyruvate, NADH
The three fates of pyruvate are
-TCA cycle, Lactic acid fermentation(muscles), alcohol fermentation in yeast
Investing ATP allows for glucose uptake to be____.
Utilizing ATP to irreversibly convert glucose to G6P allows for____
-controlled
-the regulation uptake in glucose
G6P is not allowed to cross the plasma membrane due to____
phosphorylation
What sugars can hexokinase be used for?
-glucose
-fructose
-mannose
Hexokinase has high affinity, and provides_____
direct feedback regulation by G6P.
The liver stores extra___ and doesn't compete with other tissues
glucose
What sugars can glucokinase be used for?
glucose only!!
Due to the poor affinity of glucokinase, it allows for the liver
to get what is left over
Glucokinase has a
different regulatory mechanism
What substrate is the branch point for several metabolic pathways?
G6P
How does hexokinase and glucokinase prevent ATP from reacting with water?
glucose binding (conformational change that orients glucose and ATP and excludes water)
What intermediate is formed when making G6P to F6P?
enediol intermediate
In phosphofructokinase, a decrease in ATP and an increase in AMP causes for
PFK to respond to cells energy demands and turn glycolysis on and off.
The R-state(high affinity) of PFK allows for the _____
stabilization of AMP
The T-state(low-affinity) of PFK allows for the_____
stabilization of ATP
Positive allosteric effectors shift equilibrium to favor
r-state
Negative allosteric effectors shift equilibrium to favor
t-state
PFK is first
committed step in glycolysis
PFK activity_____ when the energy status of cell is low, and _____-when the energy status is high.
-increases
-decreases
Is PFK tightly regulated?
YES
F-2,6-BP stimulates PFK by decreasing
inhibitory effects of ATP
In aldolase, each end is phosphorylated before
cleaving because its trapped
What does the aldolase enzyme found in animal tissues form into?
-covalent Schiff base E-S intermediate
What does the aldolase enzyme found in bacterial and fungi form into?
-doesn't form E-S intermediate but contains a Zn2+to help shield the oxyanion intermediate
Which carbon in glucose becomes C=O in DHAP after both aldolase and triose P isomerase?
C#2 or C#5
TPI is a near perfect enzyme because it has
high affinity/fast chemistry
In glycolysis first phase, ___ATPs are consumed. In the second phase,____ATPs are produced. Which results in a net ATP yield of __ATPs per glucose.
-2, 4, 2
Glyceraldehyde 3-phosphate dehydrogenase uses_______ as a cosubstrate which involves the exchange of electrons.
NAD+
Gly-3P is oxidized to
1,3-BPG
Phosphoglycerate kinase transfers a phosphoryl group from 1,3-bisphosphoglycerate to ADP to ATP
substrate-level phosphorylation
A___is an enzyme that catalyzes the migration of a function group within the substrate molecule
mutase
The enolase reaction in glycolysis is a
dehydration reaction, not a redox reaction
Pyruvate Kinase irreversible in vivo
.
ATP production via glycolysis doesn't require____
oxygen
What are the key regulatory steps (irreversible)?
-hexokinase/glucokinase
-phosphofructokinase
-pyruvate kinase
Flexible loop closes over TIM active site and creates
Methylglyoxal formation
What other substrates can be used for glycolysis?
fructose, galactose, and mannose
Fructose (muscle) requires____
hexokinase
A tagged glucose (UDP) must occur to
enter glycolysis
What enzymes are needed for galactose to go through glycolysis?
galactokinase, galactose-1-phosphate uridylyl transferase, UDP-galactose-4-epimerase, phosphoglucomutase
What enzymes are needed for mannose to go through glycolysis?
hexokinase and phosphomannose isomerase
What enzyme is needed for fructose to go through glycolysis in the muscle?
hexokinase
What enzymes are needed for fructose to go through glycolysis in the liver?
-fructokinase
-fructose-1-phosphate aldolase,
-glyceraldehyde kinase,
-alcohol dehydrogenase
-glycerol kinase,
-glycerol phosphate dehydrogenase,
-triose phosphate isomerase
Activators:
AMP, F16BP (more pyruvate, more ATP)
Inhibitors:
ATP(stabilize t-state), Acetyl-CoA (less pyruvate), and Alanine (carbon skeleton)
Important regulation steps in glycolysis in liver
1. glucokinase
2. PFK
3. Pyruvate kinase
Fructose only metabolizes in excess amounts by_____ and excess sugar become____
-the liver
-fat
Glycerol is produced in the decomposition of____.
-triacylglycerols
In the ethanol endpoint of glycolysis, is a 2 step process catalyzed by
-pyruvate decarboxylase
-alcohol dehydrogenase
In the lactate endpoint of glycolysis, pyruvate is reduced by _____ and is reversible
lactate dehydrogenase (larger amounts of ATP generated)
Aerobic glycolysis generates more ATP but has a ______
much slower rate
Anaerobic glycolysis generates less ATP but has a
much faster rate
What is the Cori cycle?
liver and muscle work together to keep sprinting
What type of twitch muscles do these characteristic represent?
-dark in color
-has endurance
-is aerobic
slow twitch
What type of twitch muscles do these characteristic represent?
-is anaerobic
-light in color
-fatigues easily
fast-twitch
Humans do not have_____, but they do have_____
-PDC
-ADH
Humans do not have pyruvate carboxylase, but they do use______
thiamine pyrophosphate(TPP)
Does TPP allow for a better reaction pathway?
YES

..

Mechanism of pyruvate decarboxylase
look at the mechanism
The body has enough glucose to supply for one day, so it must be made from
non-carbohydrate precursors
The brain functions on glucose and accounts for 75% of
daily consumption of glucose
Muscles also require______
glycolysis
GNG meets the body's glucose needs under_____
fasting conditions
Our brains cease to function when blood glucose concentration is_____
<2.5 mM.
Humans consume about___per day
160 g
The reactions that goes from pyruvate to TCA, occur in the
mitochondria
Body fluids contain only ___ of glucose.
Glycogen stores yield____of glucose.
-20g
-180-200g
What are the substrates for GNG?
pyruvate, lactate, glycerol, amino acids and all TCA intermediates
Acetyl-CoA cannot provide for
net synthesis of sugars
GNG has four different enzymes from glycolysis because
the conversion of Pyruvate to PEP requires two steps
Acetyl CoA is a main carbon source for TCA cycle where an increase in acetyl-coA means
cell has plenty of "fuel"

Biotin is a vitamin that serves as a
mobile CO2 carrier
Pyruvate carboxylase uses ATP to load CO2 onto ____then delivers it to ______
-biotin
-pyruvate
PEP carboxykinase uses
GTP rather than ATP
Why does cell add CO2 with pyruvate carboxylase and then take it back off with PEPCK?
decarboxylation drives the formation of the enol that GTP phosphorylates
Fructose-1,6-bisphosphatase allosteric regulation:
-citrate simulates(makes glucose)
-fructose-2,6-bisphosphate inhibits(activates PFK (glycolysis on))
-AMP inhibits (low energy)
F1,6BPase: What gets inhibited vs. activated?
-AMP inhibit (GNG off)
+ATP(allosteric site)
+Citrate (allosteric site)
-F2,6P(turns GNG off)
PFK1: What gets inhibited vs. activated?
+AMP(low energy)
-ATP (allosteric sites)(high energy)
-citrate(allosteric site)(high energy)
+F2,6P(turns GNG on)
PFK-2 domain
production
F2,6BPase domain
breakdown
the presence of G-6-Pase in ER of the ____and______ cells makes GNG possible
-kidney
-liver
Muscles and brains DO NOT do______
GNG
Glucose-6-phosphatase reaction involves_____by a histidine nitrogen and formation of a_________
-nucleophilic attack
- phosphohistidine intermediate
Vigorous exercise lead to the build up of__________due to O2 shortage and the need for more glycolysis
lactate and NADH
NADH is reoxidized during the reduction of
pyruvate to lactate
Lactate is then reduced to the liver where it can be reoxidized to
pyruvate by liver LDH
GNG is driven by the consumption of___-
6 nucleosides triphosphates
When glycolysis is turned on, GNG should be
turned off
When cell's energy status is high, glycolysis should be off and should be used for
synthesis and storage of glucose
When cells energy status is low, glucose should be rapidly
degraded to provide energy(needs ATP)
An individual is sprinting, what type of regulation is going on in terms of glycolysis and GNG?
IN THE MUSCLE
-glycolysis is on, production of ATP is critical, so anaerobic glycolysis is occurring
-ATP is being generated as quickly as possible
An individual is sprinting, what type of regulation is going on in terms of glycolysis and GNG?
IN THE LIVER
-GNG is on, production of NADH and glucose for use in muscles is critical
Pentose phosphate pathway has 2 phases:
oxidative phase and nonoxidative phase
The oxidative phase of PPP uses glucose metabolism to
help supply NADH for reductive reactions
The nonoxidative phase of PPP uses glucose metabolism to supply
ribose-5-phosphate
The first 4 substrates makes
2NADPH G6P--->5C sugar-P
The bottom substrates interconvert
3C,4C,5C,6C,7C sugars
NADH is mainly in______form and removes 2e- during fuel metabolism
oxidized
NADPH is mainly in _______form and adds 2e- during biosynthesis and detox of free radicals
reduced
PPP operates mostly in
cytoplasm of liver and adipose cells(fat)
G6P dehydrogenase is regulated by NADPH levels
-NADPH is a _____, cytosolic levels of NADP+/NADPH dictate enzymes activity
inhibitor

oxidation of an aldehyde
Hyrdolysis of lactone occurs both
enzymatically and non-enzymatically
6-phosphoglucono8-lactone is hydrolytically unstable, so it readily undergoes
spontaneous ring opening hydrolysis
reaction 2: gluconolatonase accelerates the spont. ring opening hydrolysis in order to
prevent the accumulation of 6-phosphogluconolactone which is toxic
The 2 phases of oxidative decarboxylation:
- NADP+ dependent dehydrogenation yielding a beta-keto acid
- decarboxylation event that produces ribulose-5-phosphate
Phosphopentose isomerase has an
enediol intermediate
Ribose-5-phosphate is used in biosynthesis of
coenzymes, nucleotides, and nucleic acids
Phosphopentose Epimerase change in position of acidic proton and has a
enediolate intermediate
Transketolase is the transfer of _____ from ketose(donor) to aldose(acceptor) and utilizes _____
-2-C
-TPP
Although reaction is called transketolase, the group that is transferred is a_____
aldol
Transaldolase converts ___skeleton to a useful______skeleton, and it transfers_____
- 7-C
- 6-C
- 3-C
The transaldolase mechanism involves attack on the substrate by
an active-site lysine
The nonoxidative steps consists of
-phosphopentose isomerase
-phosphopentose epimerase
-transketolase (TPP-dependent)
-transaldolase (Schiff base mechanism)
What does phosphopentose isomerase do?
coverts ketose to aldose
What does phosphopentose epimerase do?
epimerizes at C-3
What does transketolase(TPP-dependent) do?
transfer of two-carbon units
What does transaldolase do?
transfers a 3 carbon unit
What are the 5 variations of PPP?
- both ribose-5-P and NADPH are needed
- more ribose-5P than NADPH is needed
- More NADPH than ribose-5-p is needed
- NADPH and ATP are needed, but ribose-5-p is not
1) More ribose-5-P than NADPH is needed
What types of situations would call for this?
rapidly dividing cells that are synthesizing DNA
3) more NADPH than ribose-5-P is needed:
when fatty acids are being synthesized,
NADPH is consumed rapidly
4) NADPH and ATP are needed, but ribose-5-P is not
Generate intermediates for glycolysis,
producing pyruvate that can go through TCA
More than likely the goal will be_____ in PPP
ribose-5-phosphotate
Is a multi-branched polysaccharide of glucose
glycogen
What is glycogen used for?
-degraded when glucose is needed
-it is synthesized for energy
Glycogen is the readily mobilized storage form of_____
glucose
The liver has higher concentrations of glycogen stored due to controlling
blood and glucose levels (must react quickly to glucose and blood changes)
______is where most of the glycogen is stored
Muscle
The muscle consists of_____glycogen, triggers fight or flight, and quickly mobilized
1-2%
The liver is up to______glycogen.
10%
the liver must maintain about ______blood glucose.
The liver also has a 12 hour supply of_____
-5mM
-glucose
Glycogen has_____and linkages
alpha(1->6) and alpha(1->4)
Amylase is a saliva enzyme that hydrolysis the alpha(1->4) glycosidic bond of_____
starch
An enzyme that hydrolysis one glucose residue at a time and is capable of alpha(1->6) glycosidic bonds and leaves glycogen with one less point
alpha(1->6) glucosidase
An enzyme that transfers trisaccharide unit and converts it to a alpha(1->4) bond
Oligo(alpha(1->4), alpha(1->6))glucanotransferase
α-amylase is found in_____ and β-amylase is found in____
-animals
-plants
Endoglycosidase hydrolysis α(1->4) linkages which produces a
mixture of limit dextrin
Starch digestion is highly efficient and almost 100% of digested food is____ and ____-
-absorbed
-metabolized
How is degradation achieved?
by a heavily regulated enzyme (glycogen phosphorylase)
Glycogen degradation in muscles and liver indicate important energy reservoirs stored in the
-cytosol
Allows for the breakdown of glycogen into glucose1-P
glycogen phosphorylase
Glycogen phosphorylase is activated by:
-Allosteric control (local control)
-covalent modification(global control)

Glycogen phosphorylase:
ATP and glucose-6-phosphate is a________
feedback inhibitor

Glycogen phosphorylase:
The response to the concentration of the substrate_____-
-(Pi)

Glycogen phosphorylase:
____is a positive effector that binds at the same site as ATP
AMP
T-state is stabilized by____ and ________.
(high ATP signals no need for energy)
ATP and G6P
R-state: stabilized by______.
(low ATP signals a need for energy)
AMP
The breakdown of a molecule directly using phosphate
Phosphorolysis

What type of reaction is this?
Isomerization because a phosphate group is being relocated from C1 to C6
Glucose units are activated for transfer by formation of sugar nucleotides
Glycogen synthesis-I
What are other examples of activation?
aminoacyl-AMP, Fatty acyl-AMP, etc.
Glycogenin is a protein that
forms the core of a glycogen particle
In glycogen synthase, what gets kicked off?
the tag (UDP)
Glycogen synthase is allosterically regulated by:
increase in G6P, when G6P is high,
ATP levels are high, and AMP is low
Glycogen synthase is less active in the______form and more active in the______form
-phosphorylated
-dephosphorylated
90% of glycogen cleaved into G1P which is
isomerized into glucose-6-phosphate
10% are the branched residues that are hydrolyzed into glucose can than be
phosphorylated into G6P
The complete oxidation of G6Pvia glycolysis, TCA cycle and oxidative phosphorylation yields 38 molecules of ATP which means its effciency of storage is
97%
what are the 3 fates of G6P?
-glycolysis
-conversion to free glucose into blood stream (liver)
Glucose-1-phosphate cannot escape the cell because
it allows cell time to determine needed conversion
Why galactose and glycogen metabolism involve UDP?
UDP: conenzyme-like carrier of hexose groups
If O2 levels are reestablished in the muscle,
lactate can be converted to pyruvate
What are the three important hormones?
- insulin
- glycagon
- epinephrine
What is the allosteric regulation for glycogen synthase?
G6P(makes glycogen)
What is the allosteric regulation for glycogen phosphorylase?
ATP (breakdown glycogen)
If there is excess sugar and energy, there is an increase in G6P, ATP, and a decrease in AMP. This result in
making glycogen
If there is low sugar but a energy demand, there is a decrease of G6P, ATP, and an increase in AMP. This cause the
breakdown of glycogen
Insulin (high blood sugar) cAMP________ and stores glycogen and fat
decreases
Epinephrine(adrenalin)_______cAMP and give fight or flight signals as well as mobilizing glycogen
increases
Glucagon(low blood sugar) cAMP is ______ in the ______, and it mobilizes liver glycogen and sends glucose to brain
-increased
-liver
Insulin is secreted as a response to
increased glucose levels in blood
Is a peptide hormone produced from beta-cells in the pancreas
Insulin
The body utilizes different pathways that use glucose to
deplete the high concentration of glucose
When lots of glucose is about to be needed, what can aid in producing it?
epinephrine
Where is glucagon released from?
α-cells in the pancreas and travels to liver
Where is epinephrine released from?
adrenal gland
Glucagon and epinephrine inhibit glycogen synthase and activate
glucogen phosphorylase
The end goal of hormone -activated enzymatic cascade has an end goal of
activation of glycogen phosphorylase

What structure is this?
cAMP
Epinephrine activates glycogen_____ and inhibits glycogen_______.
-breakdown
-synthesis
Glucogen stimulates liver to release glucose from
glycogen stores into the blood stream
Exercise--> low blood glucose->
high cAMP
exercise requires lots of
ATP
Glucagon specifically targets the
liver
Low blood sugar-->glucagon secreted by pancreas-->
cAMP levels increase in liver
Liver's response to LBG:
- LBG
- Increased glucagon secreation
- increased cAMP
- increased enzyme phosphorylation
- ?
- ?
- ?
- ?
5. Activation of FBPase-2 and inactivation of PFK-2
6. Decreased F2,6P
7. inhibition of PFK and activation of FBpase
8. Increased GNG
Excess food+ no exercise-->
high blood glucose
Some glucose will be retained as glycogen but only 1-2% is stored, the rest must be dealt by the
liver