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Test 3 material from lecture
Test 3 material from lecture
391
Biochemistry
Undergraduate 3
02/03/2018

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Term
depiction of degrading glycogen to release glucose
Definition
[image]
Term
glycogen phosphorylase
Definition
degrades glycogen into glucose
Term
difference between muscle glycogen and liver glycogen
Definition
they are 2 isozymes (kinda 2 forms of the same enzyme), 90% identical on the amino acid level
Term
where glycogen phosphorylase can cleave glycogen
Definition
at 1,4-linkages up to 4 residues away from 1,6-linkages
Term
where branches occur in glycogen
Definition
about every 10 residues
Term
depiction of the function of glycogen phosphorylase
Definition
[image]
Term
Transferase
Definition
transfers 3 glycosyl residues onto one of the branches
Term
depiction of the function of transerase
Definition
[image]
Term
α-1,6-Glucosidase
Definition
cleaves remaining glucose (free sugar, hexokinase phosphorylates)
Term
depiction of the function of α-1,6-Glucosidase
Definition
[image]
Term
depiction of the entire degradation of glycogen
Definition
[image]
Term
phosphoglucomutase
Definition
converts glucose 1-P into a usable form, glucose 6-P
Term
depiction of the function of phosphoglucomutase
Definition
[image]

note that the phosphate ends up on a different residue
Term
what glycogen stored in liver is used for
Definition
to deliver glucose elsewhere (i.e., maintaining blood glucose levels)
Term
what glycogen stored in muscle is used for
Definition
provides glucose for its own energy demands
Term
does glucose 1-P enter glycolysis?
Definition
no
Term
are phosphorylated forms of glucose exported?
Definition
no
Term
glucose-6-phosphatase
Definition
catalyzes the dephosphorylation of glucose 6-P into glucose and Pi glucose 6-P + water --> glucose + PPi
Term
where is glucose-6-phosphatase expressed?
Definition
liver
Term
depiction of the general regulation of phosphorylase (might wanna draw this)
Definition
[image]
Term
the more active form of glycogen phosphorylase
Definition
phosphorylase a
Term
the less active form of glycogen phosphorylase
Definition
phosphorylase b
Term
how phosphorylase gets activated
Definition
phosphorylation
Term
activity of phosphorylase is modulated by...
Definition
active site binding
Term
phosphorylase kinase
Definition
phosphorylates phosphorylase
Term
how phosphorylase is deactivated
Definition
PP1 dephosphorylates it
Term
some molecules that can bind to phosphorylase to stabilize the R or T states
Definition
-ATP
-AMP
-glucose 6-P
-glucose
Term
hormones in muscle that affect phosphorylase
Definition
-adrenaline
-epinephrine
Term
how phosphorylation is stimulated in muscle
Definition
Hormones: epinephrine, adrenaline (fear/excitement), increase phosphorylation (a state) by stimulating phosphorylase kinase. Muscle contraction: Ca2+ release, increase phosphorylation (a state) by stimulating phosphorylase kinase.
Term
how muscle contraction stimulates phosphorylation in muscle
Definition
Ca2+ release
Term
Allosteric effectors that stabilize phosphorylase b, T state in muscle
Definition
- Glucose 6-P
- ATP
Term
Allosteric effector that stabilizes phosphorylase b, R state in muscle
Definition
AMP
Term
form of phosphorylase that predominates in muscle
Definition
DBT

Dephosphorylated
B form
T state
Term
depiction of how allosteric affectors regulate muscle phorphorylase b (less active)
Definition
[image]
Term
what insulin does for glycogen
Definition
signals fed state, high blood glucose, and need to synthesize glucagon
Term
what insulin does for phosphorylase
Definition
inactivates it (PP1)
Term
what glucagon does for glycogen
Definition
signals starved state, low blood glucose, and need to degrade glucagon
Term
what glucagon does for phosphorylase
Definition
activates it (kinase)
Term
when phosphorylase kinase is active
Definition
when Phosphorylated by Protein Kinase A, glucagon signal, cAMP
Term
when phosphorylase phosphatase PP1 is inactive
Definition
when bound to phosphorylase, glucose releases and activates
Term
allosteric affectors for phosphorylase in liver
Definition
glucose
Term
how glucose regulates phosphorylase
Definition
- Binds to PP1/phosphorylase, PP1 released from phosphorylase, (released PP1 more active, dephosphorylates phosphorylase)
- Binds to phosphorylase a, stabilizes T state
Term
form of phosphorylase that predominates in the liver
Definition
PAR

Phosphorylated
a form
Relaxed state
Term
depiction of how phosphorylase a is regulated in the liver
Definition
[image]
Term
proteins come in...
Definition
modules
Term
depiction of the overall regulation of phosphorylase kinase
Definition
[image]
Term
depiction of the signal transduction cascacde to activate phosphorylase
Definition
[image]
Term
what epinephrine signals to the muscle
Definition
demand for muscle contraction
Term
equation for glycogen synthesis
Definition
glycogenn + UDP-glucose --> glycogenn+1 + UDP
Term
equation for glycogen degradation
Definition
glycogenn+1 + Pi --> glycogenn + glucose 1-phosphate
Term
the product of glycogen degradation
Definition
glucose 1-P
Term
how glucose 1-P is activated
Definition
by coupling with UTP, which releases PPi
Term
UDP-glucose pyrophosphorylase
Definition
catalyzes the activation of glucose 1-P by coupling to UTP
Term
depiction of the activation of glucose 1-P by coupling to UTP
Definition
[image]
Term
depiction of synthesis of 1,4 linkages in glycogen
Definition
[image]
Term
the priming enzyme for glycogen
Definition
glycogenin
Term
cross section of glycogen showing glycogenin
Definition
[image]
Term
glycogen synthase
Definition
transfers glucose from UDP to growing glycogen chain using 1,4-linkage
Term
Branching enzyme
Definition
breaks 1,4-linkage after > 4 units and creates 1,6-linkage
Term
depiction of the creation of 1,6 linkages in glycogen to create branching
Definition
[image]
Term
advantage of branching in glycogen
Definition
gives you more sites to degrade from
Term
why would it be harder to store proteins than glycogen?
Definition
because amino acids are more reactive
Term
net rxn of glycogen synthesis
Definition
glucose + 2 ATP + glycogenn + H2O --> glycogenn+1 + ADP + 2 Pi
Term
what cAMP does to PKA
Definition
binds to it and stabilizes R state
Term
depiction of the Cori cycle (might wanna draw this)
Definition
[image]
Term
how the body recovers lactic acid into glucose
Definition
the Cori cycle

lactate enters liver to participate in gng
Term
what causes the burning sensation in muscles?
Definition
lactic acid
Term
depiction of reciprocal regulation of glycogen during exercise or fasting
Definition
[image]
Term
the regulated step in glycogen synthesis
Definition
glycogen synthase
Term
the 2 kinases that can phosphorylate glycogen synthase
Definition
-PKA
-glycogen synthase kinase
Term
What removes the phosphoryl groups from phosphorylase and glycogen synthase?
Definition
PP1
Term
what PP1 does to phosphorylase
Definition
dephosphorylates it a-->b to lower its activity
Term
what PP1 does to PKA
Definition
dephosphorylates it to lower its activity
Term
what PP1 does to glycogen synthase
Definition
dephosphorylates it b-->a to activate it
Term
the more active form of glycogen synthase
Definition
the dephosphorylated a form
Term
the less active form of glycogen synthase
Definition
the phosphorylated b form
Term
depiction of insulin regulation in liver
Definition
[image]
Term
IRS
Definition
insulin receptor substrates
Term
the function of PP1
Definition
de4phosphorylates
Term
how insulin stimulates PP1 activity
Definition
An insulin sensitive protein kinase also phosphorylates a subunit of PP1, increasing the activity of PP1.
Term
when PP1 is more active
Definition
when it's phosphorylated
Term
glycogen synthase is allosterically activated by...
Definition
glucose 6-P
Term
what glucose 6-P does to glycogen synthase
Definition
allosterically activates it
Term
PP1 is bound to ______ – this keeps PP1 from ______
Definition
liver phosphorylase a
dephosphorylating phosphorylase
Term
is phosphorylase more or less active after eating pasta?
Definition
less active because of all that glucose from the pasts
Term
is phosphorylase phosphorylated or dephosphorylated after eating pasta?
Definition
dephosphorylated
Term
is PP1 more or less active after eating pasta?
Definition
I think more active
Term
depiction of how PP1 allows for "crosstalk" between phosphorylase and glycogen synthase (draw this)
Definition
[image]

it seems excess glucose cleaves the PP1 from phosphorylase so PP1 can dephosphorylase glycogen synthase and glycogen phosphorylase
Term
the dual role of PKA
Definition
activates glycogen phosphorylase and deactivates glycogen synthase, both by phosphorylation
Term
depiction of regulation of glycogen synthesis after a meal or at rest (draw this)
Definition
[image]
Term
when a lot of glycogen synthesis occurs
Definition
after a meal or at rest
Term
the role of liver glycogen metabolism
Definition
maintains blood glucose level
Term
normal range of blood glucose concentration
Definition
4.4-6.7 mM
Term
one way to tell if someone's diabetic
Definition
the whopping amount of glucose they give you stays high
Term
depiction of glycogen phosphorylase and glycogen synthase activity in response to added glucose
Definition
[image]
Term
what glucose does to glycogen phosphorylase a
Definition
releases PP1 from it
Term
PP1 is activated by...
Definition
insulin-sensitive protein kinase
Term
how activation of PP1 by insulin sensitive protein kinase leads to less phosphorylase activity
Definition
because less of it gets activated
Term
what PP1 does to phosphorylase
Definition
deactivates it from a to b by dephosphorylation
Term
what PP1 does to glycogen synthase
Definition
activates it from b to a by dephosphorylation
Term
what can activate glycogen synthase other than PP1?
Definition
glucose 6P
Term
which stays more constant throughout the day? glucose or A1c?
Definition
A1c
Term
A1c is an indication of...
Definition
the amount of glucose that becomes associated with hemoglobin; glycated with hemoglobin
Term
where non-enzymatic glycosylation takes place
Definition
in all proteins with a free-reacting lysine or valine in the presence of glucose
Term
what part of hemoglobin reacts with glucose?
Definition
the amino terminus of the beta chain
Term
why glycosylated hemoglobin is a widely used reporter for blood glucose levels
Definition
because red blood cells last 2-3 months and replenished continuously
Term
diabetes simply stated
Definition
stuck in a glucose insensitive state

the body always thinks it's starved of glucose
Term
description of type 1 diabetes
Definition
autoimmune disease resulting in destruction of insulin producing cells.
Term
description of type 2 diabetes
Definition
Insulin-resistance, insulin is usually made at normal levels but is not utilized properly, and glycogen synthesis is 50% lower.
Term
physiological response to diabetes
Definition
glucose starvation
Term
what the body can't do when it has diabetes
Definition
can't convert glucose to glycogen
Term
what happens to excess glucose when you have diabetes?
Definition
that excess glucose gets incorporated into other pathways
Term
some problems that can be caused by excess glucose
Definition
-nerve damage
-cataracts
Term
About ______ of the US population has Type 2 diabetes.
Definition
8%
Term
About 80% of people with Type 2 diabetes are ______.
Definition
obese
Term
one possible treatment for type 2 diabetes
Definition
increasing production of glucose transporters to get more glucose out of the bloodstream
Term
to activate glycogen synthesis, you wanna deactivate...
Definition
PKA
Term
increasing activity of ______ should create more active form of glycogen synthase
Definition
PP1
Term
2 things that activate PP1
Definition
-glycogen phosphorylase a
-insulin-sensitive protein kinase
Term
what releases PP1 from glycogen phosphorylase a?
Definition
glucose
Term
the key enzyme when there's a need to synthesize glycogen
Definition
PP1
Term
Hydrolysis of _____ drives the formation of UDP-glucose used in glycogen synthesis.
Definition
P-Pi this is true because of Le Chatlier's principle
Term
The core of glycogen contains ______.
Definition
glycogenin
Term
Glycogen synthase is converted into more active form by the enzyme _______ .
Definition
PP1

more active when dephosphorylated
Term
Insulin stimulates glycogen synthase activity and decreases ______ activity.
Definition
phosphorylase a

this is because phosphorylase degrades glycogen and insulin signals making glycogen
Term
Phosphorylation has the __________ affect on the enzymatic activities of glycogen phosphorylase and glycogen synthase.
Definition
opposite
Term
During fasting, _____ acts along with glycogen synthase kinase to phosphorylase glycogen synthase, ____ glycogen synthase activity.
Definition
PKA
decreasing
Term
adipocyte
Definition
cell that stores lipids; fat cell
Term
depiction of an adipocyte
Definition
[image]
Term
general pathway of triacylglycerol metabolism
Definition
[image]
Term
metabolism of triacylglycerol in the fat cell is stimulated by...
Definition
glucagon or epinephrine
Term
some lipoprotein complexes
Definition
-HDL
-LDL
-VLDL
-serum albumin
Term
is HDL cholesterol?
Definition
not really, but has cholesterol in it
Term
something bad LDL does
Definition
triggers inflammatory response in vessels, leading to vessel sclerosis
Term
triacylglycerol can be converted into...
Definition
-glycerol
-fatty acids
Term
what converts triacylglycerol into glycerol or fatty acids?
Definition
lipases
Term
pathways that glycerol that enters liver cells can get incorporated into
Definition
-glycolysis
-gng
Term
pathways that fatty acids that enter cells outside the liver can get incorporated into
Definition
fatty acid oxidation, leading to citric acid cycle
Term
lipase
Definition
converts triacylglycerol into glycerol and fatty acids
Term
structure of triacylglyceride
Definition
[image]
Term
structure of glycerol
Definition
[image]
Term
structure of fatty acids
Definition
[image]
Term
depiction of triacylglyceride being converted into fatty acids and glycerol
Definition
[image]
Term
Triacylglycerol is stored in...
Definition
adipocytes as lipid droplets
Term
how epinephrine and glucagon signal for energy
Definition
by acting through 7TM receptors, stimulate lipid breakdown or lipolysis.
Term
depiction of pathway by which a hormone signals for triacylglycerol degradation (diagram this into something that makes better sense)
Definition
[image]
Term
hormones that can signal for triacylglycerol degradation
Definition
-epinephrine
-glucagon
Term
Glycerol released during lipolysis is absorbed by the liver or other cells for use in...
Definition
glycolysis or gluconeogenesis
Term
depiction of glycerol metabolism
Definition
[image]
Term
fatty acids are linked to ______ before they are oxidized
Definition
CoA
Term
the first stage of fatty acid oxidation is basically...
Definition
conversion of fatty acid to acyl CoA
Term
acyl CoA synthetase
Definition
catalyzes the conversion of fatty acid to acyl CoA
Term
where the first stage of fatty acid degradation occurs
Definition
on outer mitochondrial membrane
Term
depiction of stage 1 of fatty acid degradation
Definition
[image]
Term
depiction of an acyl adenylate
Definition
[image]
Term
depiction of acyl CoA
Definition
[image]
Term
structure of an acyl group
Definition
[image]
Term
depiction of stage 2 of fatty acid degradation
Definition
[image]
Term
depiction of how fatty acids, in the form of acyl, cross the inner mitochondrial membrane
Definition
[image]
Term
why buying cartinine is nuts
Definition
because we can make it and there's lots of food we eat that contains it
Term
depiction of stage 3 of fatty acid degradation
Definition
[image]
Term
the rxn for one round of β-oxidation of a fatty acid
Definition
Cn-acyl CoA + FAD + NAD+ + H2O + CoA --> Cn-2-acyl CoA + FADH2 + NADH + acetyl CoA + H+
Term
the complete rxn for palmitoyl CoA
Definition
palmitoyl CoA + 7 FAD + 7 NAD+ + 7 H2O + 7 CoA --> 7 FADH2 + 7 NADH + 8 acetyl CoA + 7 H+
Term
How much ATP is generated from C16 palmitoyl-CoA?
Definition
net 106

produces 108 at the expense of 2
Term
depiction of how ketone bodies are formed
Definition
[image]
Term
when formation of ketone bodies occurs
Definition
basically happens when acetyl CoA goes wild
Term
the 2 ketone bodies that can be produced
Definition
-acetone
-D-3-hydroxybutyrate
Term
when production of acetone occurs
Definition
basically happens as a result of running out of citric acid cycle intermediates
Term
what happens to acetone?
Definition
2-30% lost in breath and urine.

during starvation, some converted to pyruvate, enters gluconeogenesis
Term
depiction of how D-3-hydroxybutyrate can be used for energy
Definition
[image]
Term
some tissues that can use ketone bodies as fuel
Definition
-liver
-heart
-renal cortex
-brain
Term
choice of fuel vs. days of starvation
Definition
[image]
Term
the first thing that goes during starvation
Definition
glycogen
Term
depiction of Diabetic ketosis (ketoacidosis)
Definition
[image]
Term
how ketoacidosis occurs
Definition
-physiology thinks you have no glucose in your bloodstream
-this can happen when you produce no insulin
-this results in lots of acetone
Term
depiction of the pathways that contribute to fatty acid synthesis
Definition
[image]
Term
when you make fatty acids, you have big demand for...
Definition
reducing power
Term
NADP v NAD
Definition
rule of thumb: NADPH in biosynth and NADH in catabolism
Term
stage 1 of fatty acid synthesis
Definition
transfer citrate from the mitochondria to the cytoplasm, cleaved to form acetyl CoA and OAA (ATP citrate lyase)
Term
stage 2 of fatty acid synthesis
Definition
activation of acetyl CoA + carbonate to form malonyl CoA

Key regulatory and committed step (acetyl CoA carboxylase)
Term
stage 3 of fatty acid synthesis
Definition
repetitive addition and reduction of two carbon units to synthesize fatty acids.

Synthesis occurs on an acyl carrier protein (ACP), which acts as a molecular scaffold (can also think of it as a tag).
Term
which occurs in fatty acid synthesis? reduction or oxidation?
Definition
reduction
Term
which occurs in fatty acid synthesis? hydration or dehydration?
Definition
dehydration
Term
which occurs in fatty acid degradation? reduction or oxidation?
Definition
oxidation
Term
which occurs in fatty acid degradation? hydration or dehydration?
Definition
hydration
Term
depiction of stage 1 of fatty acid synthesis
Definition
[image]
Term
acetyl CoA carboxylase
Definition
catalyzes synthesis of malonyl CoA
Term
depiction of stage 2 of fatty acid synthesis
Definition
[image]
Term
Fatty acid synthase
Definition
catalyzes the formation of fatty acids
Term
where fatty acid synthesis occurs
Definition
on the acyl carrier protein (ACP), a polypeptide linked to CoA
Term
depiction of stage 3 of fatty acid synthesis
Definition
[image]
Term
depiction of round 1 of stage 3 of fatty acid synthesis
Definition
[image]
Term
depiction of round 2 of stage 3 of fatty acid synthesis
Definition
[image]
Term
the activities of fatty acid synthase
Definition
-condensation
-reduction
-dehydration
-reduction
Term
fatty acid synthesis keeps running until...
Definition
you get to C16
Term
regulators of acetyl CoA carboxylase
Definition
-citrate
-malonyl CoA
-fatty acid (in this case, palmitoyl CoA)
Term
when acetyl CoA carboxylase is inhibited
Definition
when phosphorylated by AMP-dependent protein kinase (AMPK)
Term
how acetyl CoA carboxylase gets activated
Definition
gets dephosphorylated by protein phospahatase 2A (PP2A)
Term
the hub of fatty acid biosynthesis
Definition
acetyl CoA carboxylase
Term
what citrate signals
Definition
fullness
Term
how citrate activates carboxylase
Definition
by facilitating the formation of active polymers of the enzyme
Term
citrate inhibits...
Definition
phosphofructokinase, lowers flux through glycolysis
Term
major end product of fatty acid biosynthesis
Definition
palmitoyl CoA
Term
how palmitoyl CoA inhibits carboxylase
Definition
by causing depolymerization of the enzyme polymers
Term
how palmitoyl CoA affects citrate
Definition
Inhibits export of citrate from mitochondria
Term
Malonyl CoA is the product of...
Definition
acetyl CoA carboxylase
Term
what malonyl CoA does to carnitine acyl transferase 1
Definition
inhibits it
Term
depiction of Regulation by AMPK and PP2A
Definition
[image]
Term
this is basically the fuel gage for fatty acid metabolism
Definition
AMP-activated protein kinase
Term
what insulin signals in fatty acid metabolism
Definition
fed state, basically signaling to synthesize fatty acids
Term
depiction of the involvement of citrate in fatty acid metabolism
Definition
[image]
Term
depiction of palmitoyl CoA inhibiting fatty acid synthesis
Definition
[image]
Term
how carboxylase inhibits fatty acid degradation
Definition
it's product, malonyl CoA, prevents the entry of fatty acid acyl CoA into mitochondria by inhibiting carnitine acyl transferase I
Term
depiction of malonyl CoA (product of carboxylase) inhibiting fatty acid degradation
Definition
[image]
Term
general depiction of the synthesis of storage lipids and cholesterol
Definition
[image]
Term
depiction of a cell membrane with cholesterol in it
Definition
[image]
Term
structure of a cholesterol molecule
Definition
[image]
Term
phosphatidate is a precursor to...
Definition
-storage lipids
-many membrane lipids
Term
Phosphatidate is formed by...
Definition
the addition of two fatty acids to glycerol 3-phosphate in the liver.
Term
where phosphatidate formation occurs
Definition
liver
Term
depiction of phosphatidate formation
Definition
[image]
Term
structure of phosphatidate
Definition
[image]
Term
what phosphatidate can be used for
Definition
can be used to make lipids, such as phospholipids
Term
Triacylglycerol synthase
Definition
synthesizes triacylglycerol from phosphatidate and acyl CoA.
Term
the primary fuel storage in humans
Definition
triacylglycerols
Term
depiction of metabolism of phosphatidate into phospholipids and triacylglycerols
Definition
[image]
Term
depiction of phospholipid synthesis
Definition
[image]
Term
depiction of triacylglycerol synthesis
Definition
[image]
Term
most of the fat droplet in adipocytes is...
Definition
triacylglycerols
Term
something cholesterol helps with in the membrane
Definition
helps form lipid rafts, which help with lots of functions in the membrane
Term
why you should never put a baby on a low cholesterol diet
Definition
because they need cholesterol to form lipid rafts
Term
depiction of cholesterol synthesis
Definition
[image]
Term
steroid hormones are derived from...
Definition
cholesterol
Term
some steroid hormones derived from cholesterol
Definition
-androgens
-glucocorticoids
Term
cortisol is derived from...
Definition
cholesterol
Term
drugs used to lower cholesterol
Definition
statins
Term
how statins lower cholesterol
Definition
inhibit HMG CoA reductase
Term
The rate of synthesis of HMG CoA reductase mRNA is controlled by...
Definition
the sterol regulatory element binding protein (SREBP). Too little cholesterol.
Term
The rate of translation of the reductase mRNA is controlled by...
Definition
metabolites of mevalonate and dietary cholesterol (molecular mechanism not understood)
Term
Increases in cholesterol concentration result in...
Definition
proteolytic degradation of the reductase.
Term
how HMG CoA reductase is inactivated
Definition
Phosphorylation of the reductase by AMP-dependent protein kinase inactivates the enzyme.
Term
depiction of transcription control
Definition
[image]
Term
depiction of Degradation of HMG CoA reductase in response to cholesterol
Definition
[image]
Term
role of ubiquitin in the Degradation of HMG CoA reductase in response to cholesterol
Definition
acts as a tag for protein degradation
Term
the role of Degradation of HMG CoA reductase in response to cholesterol
Definition
this is basically the protein turnover machine in cells

triggered by changes in cholesterol
Term
depiction of Phosphorylation of HMG-CoA reductase
Definition
[image]
Term
ethanol metabolism in liver leads to excess...
Definition
NADH and fatty acids
(fatty liver)
Term
why it's not good to have acetylaldehyde in the system
Definition
because it is highly reactive and messes with lots of things; can even mess with DNA
Term
rxns that occur during ethanol metabolism
Definition
[image]
Term
the role of acetyl CoA synthase in fatty acid synthesis
Definition
produces acetyl-CoA from the acetate derived from ethanol (think of it as a very very short fatty acid!)
Term
how acetyl-CoA can be used for fatty acid synthesis
Definition
by converting to malonyl-CoA (acetyl-CoA carboxylase) after substituting CoA with ACP (acetyl transacylase).
Term
Consequences of acetaldehyde (very reactive)
Definition
- Damages DNA, leads to esophageal cancer
- Outcomes depend on personal genetics
Term
depiction of the flowchart of what happens as a result of too much acetaldehyde
Definition
[image]
Term
what acetaldehyde does to DNA
Definition
causes DNA strands to crosslink
Term
depiction of the different fates of pyruvate
Definition
[image]
Term
Excess NADH/acetate inhibits...
Definition
inhibits citric acid cycle

NADH inhibits α KG dehydrogenase and isocitrate dehydrogenase
Term
Excess NADH/acetate stimulates...
Definition
-lactic acidosis; excess NADH pushes lactate dehydrogenase rxn towards lactate
-fatty acid synthesis due to excess acetyl-CoA; leads to fatty liver
-ketone body formation as a result of more acetyl-CoA; this leads to more acidosis
Term
why some people are more vulnerable to alcohol induced cancer
Definition
because they have an allele that increases acetaldehyde production when drinking alcohol
Term
depiction of the Molecular basis of the ALDH2*E487K variant
Definition
[image]
Term
why do we not store amino acids or proteins?
Definition
amino acids are more diverse and therefore proteins are more complex and less stable
Term
What happens to the ammonia produced when amino acids are used as fuel?
Definition
gets converted to urea, because it's toxic
Term
the 1st step in the degradation of amino acids
Definition
N removal
Term
how N gets removed from amino acids
Definition
alpha amino groups are converted into ammonium ions by the oxidative deanimation of glutamate Amino groups from amino acids are funneled to glutamate, which is deaminated to form NH4+.
Term
depiction of N being removed from amino acids
Definition
[image]
Term
what degrades proteins?
Definition
proteases
Term
what degrades glutamate?
Definition
I think glutamase
Term
Aminotransferases (transaminases)
Definition
transfer amino groups from an amino acid to α-ketoglutarate to generate glutamate.
Term
depiction of the function of aminotransferases (transaminases)
Definition
[image]
Term
Glutamate dehydrogenase
Definition
a mitochondrial enzyme, releases NH4+ in the oxidative deamination of glutamate
Term
depiction of the function of glutamate dehydrogenase
Definition
[image]
Term
why you gotta regulate how much glutamate is produced
Definition
because glutamate is also a neurotransmitter
Term
allosteric regulators of glutamate dehydrogenase
Definition
- GTP and ATP Inhibit
- GDP and ADP Activate
Term
what GTP and ATP do to glutamate dehydrogenase
Definition
Inhibit it
Term
what GDP and ADP do to glutamate dehydrogenase
Definition
Activate it
Term
depiction of the major flow of ammonia
Definition
[image]

note that it gives you ONE of the N's in urea
Term
depiction of how NH4+ is processed in the liver
Definition
[image]
Term
how muscle processes NH4+
Definition
- Lacks urea cycle
- Transaminations to Alanine, which is exported to the liver to be converted to glutamate
Term
do muscle cells have a urea cycle?
Definition
no
Term
how do muscle cells get around not having a urea cycle?
Definition
Transaminations to Alanine, which is exported to the liver to be converted to glutamate
Term
depiction of the urea cycle (draw this)
Definition
[image]
Term
understand these things about pathways:
Definition
1: function
2: energetics
3: regulation
4: compartmentalized?
5: pathway connections
Term
the types of molecules citrulline and ornithine are
Definition
amino acids, but they're never used to make proteins
Term
function of urea cycle
Definition
to get rid of ammonia by producing urea
Term
energetics of urea cycle
Definition
urea cycle consumes energy (note that it consumes ATP)
Term
how is the urea cycle compartmentalized?
Definition
mitochondria and cytoplasm
Term
pathway connection from urea cycle
Definition
fumarate can go to gng
Term
Carbamoyl phosphate synthase
Definition
Couples ammonia to bicarbonate
Term
allosteric activator of Carbamoyl phosphate synthase
Definition
N-Acetylglutamate
Term
how arginine affects urea cycle
Definition
high concentration of arginine activates the Urea cycle
Term
depiction of the function of Carbamoyl phosphate synthase (how Carbamoyl phosphate is synthesized)
Definition
[image]
Term
Ornithine transcarbamoylase
Definition
forms citrulline from ornithine and carbamoyl phosphate
Term
depiction of the function of Ornithine transcarbamoylase (how ornithine is converted to citrulline)
Definition
[image]

the pink is what becomes urea
Term
how citrulline and ornithine are thansported accross the mitochondrial membrane
Definition
co-transport of ornithine (in) and citrulline (out)
Term
Arginosuccinate synthase
Definition
condenses citrulline and aspartate
Term
depiction of the function of Arginosuccinate synthase (how arginosuccinate is synthesized)
Definition
[image]
Term
Argininosuccinase
Definition
degrades arginosuccinate into arginine and fumarate

fumarate enters gng
Term
depiction of the function of Argininosuccinase
Definition
[image]
Term
arginase
Definition
catalyzes hydrolysis of arginine into ornithine and urea
Term
the rxn arginase is involved in
Definition
Arginine + water --> ornithine + UREA
Term
where do the N's in urea come from?
Definition
aspartate and ammonium
Term
the urea cycle is linked to...
Definition
gng
Term
how the urea cycle is linked to gng
Definition
CO2 + NH4+ + 3 ATP + aspartate + 2 H2O --> urea + 2 ADP + 2 Pi + AMP + PPi + fumarate the fumarate can enter gng
Term
depiction of what links gng and the urea cycle
Definition
[image]
Term
depiction of the fates of C backbones of amino acids in metabolism
Definition
[image]

the yellow are ketogenic and the pink are glucogenic
Term
______ are required for degradation of aromatic amino acids
Definition
oxygenases
Term
aromatic amino acids require ______ for degradation
Definition
monooxygenases (mixed-function oxygenases)
Term
what monooxygenases use as substrates
Definition
O2
Term
what monooxygenases do
Definition
use O2 as a substrate and incorporate one O into theproduct and the other into water
Term
phenylalanine hydroxylase
Definition
monooxygenase that converts phenylalanine into tyrosine with the assistance of the cofactor tetrahydrobiopterin
Term
depiction of the function of phenylalanine hydroxylase (conversion of phenylalanine to tyrosine)
Definition
[image]
Term
something deficient in Phenylketonuria (PKU)
Definition
PAH (or biopterin)
Term
the genetics details of the PKU allele
Definition
- Recessive
- about 1/60 carriers
- about 1/15,000 live births
Term
PKU causes mental retardation. the mechanism is unknown, but what's one possibility?
Definition
if the phenylalanine c'tration gets too high, it causes neurological damage by preventing uptake of some amino acids into the brain
Term
depiction of phenylalanine and tyrosine degradation
Definition
[image]
Term
why phenylalanine and tyrosine have glucogenic character as well as ketogenic character
Definition
because degradation produces acetone and fumarate; the fumarate can enter gng pathway
Term
what causes PKU?
Definition
missing or deficient phenylalanine hydroxylase
Term
in PKU, some of the excess phenylalanine is converted into...
Definition
phenylpyruvate
Term
how to diagnose PKU
Definition
urine turns green with FeCl3
Term
what happene when someone is diagnosed with PKU?
Definition
put on strict diet to prevent mental retardation
Term
molecular basis of PKU
Definition
current hypothesis: excess Phenylalanine blocks a large neutral amino acid transporter at the blood brain barrier called LAT-1
Term
depiction of conversion of phenylalanine into phenylpyruvate
Definition
[image]
Term
can we synthesize phenylalanine?
Definition
no
Term
important characteristic of a PKU patient's diet
Definition
must avoid too much phenylalanine, but phenylalanine is an essential amino acid, so we must consume some of it
Term
Biosynthetic families of amino acids in bacteria and plants
Definition
[image]

the ones with E are essential for humans
Term
depiction of the synthesis of serine and glycine
Definition
[image]
Term
why it's bad to have too much homocystein in the system
Definition
oxidizes:
- Blood vessel lining
- Vascular smooth muscle
Term
depiction of the synthesis of homocysteine and cysteine
Definition
[image]
Term
something used frequrntly in biosynthetic pathways
Definition
One carbon donors/acceptors
Term
why S-adenosylmethionine (SAM) is an effective methyl group donor
Definition
because the positive charge on S gives it higher methyl transfer potential
Term
depiction of synthesis of S-adenosylmethionine (SAM)
Definition
[image]
Term
when fasting, why is there an initial surge of N excretion?
Definition
utilization of dietary protein
Term
Why does nitrogen excretion fall after several weeks of fasting?
Definition
using fatty acids, and then ketone bodies
Term
why there's an increase in nitrogen secretion when the lipid stores are depleted
Definition
starts degrading your own proteins; last ditch effort
Term
Which of the following compounds serves as an acceptor for amino groups of many
amino acids during catabolism? Glutamine, Asparagine, Alpha-ketoglutarate, or Histidine
Definition
alpha-ketoglutarate
Term
PKU can be caused by...
Definition
deficiency phenylalanine hydroxylase or tetrahydrobiopterin
Term
PKU leads to...
Definition
buildup of phenylalanine in the body
Term
how PKU causes mental retardation
Definition
unknown
Term
two examples of direct transmination between CAC intermediates and amino acids
Definition
alpha-ketoglutarate --> glutamate

oxaloacetate --> aspartate
Term
Can an amino acid be both ketogenic and glucogenic?
Definition
yes
Term
an unborn baby's neural tube closure requires lots of...
Definition
tetrahydrofolate
Term
Triacylglycerols are stored in _____ in mammals
Definition
adipocytes
Term
Feedback inhibition usually occurs at the ______ step in a biosynthetic pathway.
Definition
committed
Term
Degradation of ketogenic amino acids gives rise to _______.
Definition
-acetyl CoA
-acetoacetyl CoA
Term
Carnitine is the carrier used to transfer fatty acids into the _______ for degradation.
Definition
mitochondrion
Term
Complete beta oxidation of myristyl-CoA (14:0) yields
Definition
7 acetyl CoA + 6 FADH2 + 6 NADH + 6 H+
Term
Fatty acid synthesis begins with the export of ______ from the mitochondria.
Definition
citrate
Term
Fatty acid synthesis adds a total of ___ carbon units per cycle after removal of ___ unit(s) as CO2.
Definition
2 1 you add 3, but lose 1 as CO2, so the net is 2, 1
Term
Fatty acid synthesis and degradation occurs using similar intermediates. What allows these pathways to function independently without a creating a futile cycle?
Definition
-Synthesis occurs in the cytoplasm, degradation in the mitochondria.
-Acyl-carnitine used for degradation.
-Acyl-ACP used for synthesis
Term
Type 2 diabetes is a condition where insulin is produced but cannot perform its function (insulin resistance), allowing blood glucose levels to remain above normal. Research is underway to develop drugs for glycogen phosphorylase as a possible treatment. Provide a rationale for this strategy.
Definition
A drug that inhibits phosphorylase should reduce the level of glucose.
Term
Excessive alcohol consumption results in abnormally high levels of...
Definition
NADH
Term
The level of HMG-CoA reductase is regulated by...
Definition
-protein degradation mediated by the proteasome.
-transcription of the HMG-CoA reductase gene in response to low levels of sterols.
-the level of protein phosphorylation modulated through signaling pathways.
Term
Increasing the level of insulin secretion should stimulate ____.
Definition
cholesterol and glycogen synthesis
Term
Under what physiological condition would acetyl CoA carboxylase and HMG CoA reductase be phosphorylated by AMP-activated protein kinase?
Definition
A starved state should increase phosphorylation of these enzymes, lowering their activity.

under starved state, you wanna degrade, not synthesize, stuff
Term
What role does acetyl CoA carboxylase play in fatty acid degradation?
Definition
The product of acetyl CoA carboxylase, malonyl-CoA, inhibits acyl carnitine transferase I import of acyl carnitine into the mitochondria where fatty acid degradation occurs
Term
how protein phosphatase 1 (PP1) regulates glycogen synthesis in liver
Definition
-Glucose releases PP1, where it dephosphorylates phosphorylase A to form the less active form phosphorylase B.
-Inactivates phosphorylase kinase by dephosphorylation.
-Activates glycogen synthase by dephosphorylation
Term
The urea cycle removes ____ atoms of nitrogen per cycle
Definition
2

1 coming from ammonium and the other coming from the amino group of aspartate
Term
two pathways that contribute precursors for amino acid synthesis
Definition
-glycolysis
-citric acid cycle
Term
How might increased synthesis of glutamate and aspartate affect energy production in the cell?
Definition
Loss of oxaloacetate and alpha ketoglutarate would slow the citric acid cycle.
Term
Nitrogen is funneled through _____ prior to entering the urea cycle
Definition
glutamate
Term
Statins lower cholesterol levels because they partially inhibit the committed step in cholesterol biosynthesis catalyzed by ______.
Definition
HMG-CoA reductase
Term
common site of regulation in feedback inhibition
Definition
the committed step
Term
depiction of feedback inhibition
Definition
[image]
Term
which step is usually the committed step?
Definition
the first step using the first enzyme
Term
what you gotta give bacteria for them to grow
Definition
the end product of the pathway
Term
3-phosphoglycerate dehydrogenase
Definition
catalyzes the committed step in serine synthesis
Term
The committed step in serine synthesis, catalyzed by 3-phosphoglycerate dehydrogenase, is inhibited by...
Definition
serine
Term
3-phosphoglycerate is an intermediate of...
Definition
glycolysis
Term
structure of 3-phosphoglycerate dehydrogenase
Definition
[image]
Term
how binding of serine affects 3-phosphoglycerate dehydrogenase
Definition
decreases Vmax by conformational changes that alter the active site of the catalytic domain
Term
kinetics graph of serine as an inhibitor (might wanna draw this)
Definition
[image]

this is kinda cooperativity turned on its head to analyze the inhibitor
Term
types of feedback that can occur in branched pathways
Definition
-feedback inhibition (plus) activation
-enzyme multiplicity
-cumulative feedback inhibition
Term
Feedback inhibition (plus) activation
Definition
If two pathways have an initial common step, one pathway is inhibited by its own product and stimulated by the product of the other pathway. Threonine deaminase illustrates this type of regulation.
Term
Enzyme multiplicity
Definition
The committed step is catalyzed by two or more enzymes with differing regulatory properties. For example, three distinct aspartate kinases control the synthesis of threonine, methionine, and lysine in E. coli.
Term
Cumulative feedback inhibition
Definition
A common step for several pathways is inhibited by each of the various end products. One issue is the number of allosteric sites. The Amino Acid Case is an example of this type of feedback inhibition.
Term
depiction of feedback inhibition and activation in a branched pathway
Definition
[image]
Term
one advantage of inhibition and activation by a branched pathway
Definition
in the end, you want a balance of products
Term
depiction of enzyme multiplicity in a branched pathway
Definition
[image]
Term
a microbe that can degrade raw biomass
Definition
Caldicellulosiruptor bescii, isolated from a thermal spring in Russia
Term
objective of degrading raw biomass
Definition
to produce bioethanol
Term
advantage C. Bescii has when it come to the bioethanol production process
Definition
you heat it up to about 75°C, which frees up some useful carbohydrates and it's a temp the microbe likes
Term
fermentative pathways in C. bescii for hexose sugars
Definition
[image]
Term
strategy in engineering C. bescii for use in bioethanol production
Definition
Targeted insertion and expression of C. thermocellum adhE in C. bescii
Term
what knocking out the Idh gene in C. bescii does
Definition
means no lactate
Term
another characteristic that makes C. bescii more suitable for ethanol production
Definition
C. bescii itself is fairly tolerant to ethanol tolerant to 300 mM
Term
Amino acid synthesis is generally regulated by...
Definition
allosteric interactions.
Term
In a linear biosynthetic pathway, what step is usually regulated? What molecule is usually the feedback inhibitor? Why?
Definition
Committed step
end product
saves energy

pathway won't function if committed step is inhibited
Term
If an animal is fed N15-labeled aspartate, name a major compound that will be labeled.
Definition
urea
Term
Feeding past a nutritional block resulting from a mutation is an effective way to understand ____ .
Definition
gene/enzyme relationships
Term
structure of acetyl CoA
Definition
[image]
Term
structure of triacylglyceride
Definition
[image]
Term
structure of carboxylic acid
Definition
[image]
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