Exam 4 - POSSIBLE REVIEW INFO from 22 Flashcards
Metabolism involves
catabolic reactions that break down large, complex molecules to provide energy and smaller molecules.
anabolic reactions that use ATP energy to build larger molecules.
break down large, complex molecules to provide energy and smaller molecules.
catabolic reactions
use ATP energy to build larger molecules.
anabolic reactions
Catabolic reactions are organized in stages
Stage 1, 2, 3?
Stage 1: Digestion and hydrolysis break down large molecules to smaller ones that enter the bloodstream.
Stage 2: Within the cells, degradation breaks down molecules to two- and three-carbon compounds.
Stage 3: Oxidation of small molecules in the citric acid cycle and electron transport provides ATP energy.
Catabolic reactions
Stage 1:
Digestion and hydrolysis break down large molecules to smaller ones that enter the bloodstream.
Catabolic reactions
Stage 2:
Within the cells, degradation breaks down molecules to two- and three-carbon compounds.
Catabolic reactions
Stage 3:
Oxidation of small molecules in the citric acid cycle and electron transport provides ATP energy.
The ATP molecule, composed of
the base adenine, a ribose sugar, and three phosphate groups, hydrolyzes to form ADP and AMP along with a release of energy.
A. used in anabolic reactions
B. the energy-storage molecule
C. combined with energy-requiring reactions
ATP
What are the Important Coenzymes in Metabolic Pathways?
NAD+
NADP+
FAD
Coenzyme A
Coenzyme A (CoA) is made up of several components:
pantothenic acid (vitamin B5), phosphorylated ADP, and aminoethanethiol.
NAD+
nicotinamide adenine dinucleotide
is an important coenzyme in which the vitamin niacin provides the nicotinamide group, which is bonded to ribose and the nucleotide adenosine diphosphate (ADP).
NAD+
is required in dehydrogenation reactions that produce carbon–oxygen double bonds, such as the oxidation of alcohols to aldehydes and ketones.
NAD+
NADP+
nicotinamide adenine dinucleotide phosphate
is used in anabolic reactions, such as lipid and nucleic acid synthesis.
is reduced to form NADPH
NADP+
Used in phosphate pentose pathway… a coenzyme only used here…
NADP+ or NADPH
FAD name?
flavin adenine dinucleotide
contains ADP and riboflavin (vitamin B2).
undergoes reduction when the two nitrogen atoms in the flavin part of the FAD coenzyme react with two hydrogen atoms (2H+ + 2 e−), reducing it to FADH2.
Coenzyme FAD, flavin adenine dinucleotide
The coenzyme FAD (flavin adenine dinucleotide) made from riboflavin (vitamin B2) and adenosine diphosphate is reduced to
FADH2 by adding two hydrogen atoms.
participates in reactions that produce a carbon-carbon double bond.
is reduced to FADH2 with the aide of enzyme succinate dehydrogenase.
Think Succinate —> Fumarate
FAD, flavin adenine dinucleotide
is derived from a phosphorylated ADP and pantothenic acid bonded by an amide bond to aminoethanethiol, which contains the —SH reactive part of the molecule.
Coenzyme A
Important functions of coenzyme A include
preparation of small acyl groups such as acetyl for reactions with enzymes.
production of the energy-rich thioester acetyl CoA.
which steps for all pathways do we need FAD?
What about NAD?
What about NADP?
If you can’t think of every cycle then go back and look
complex II of ETC?
Complex II consists of the enzyme succinate dehydrogenase from the citric acid cycle.
In complex II,
CoQ obtains hydrogen and electrons directly from FADH2. This produces CoQH2 and regenerates the oxidized coenzyme FAD, which becomes available to oxidize more substrates.
Difference between ETC and oxidative phosphorylation?
Complexes I through IV are ETC, but the oxidative phosphorylation is complex V
In the chemiosmotic model,
H+ cannot move through the inner membrane but returns to the matrix by passing through a fifth protein complex in the inner membrane called ATP synthase (also called complex V).
the flow of H+ from the intermembrane space through the ATP synthase generates energy that is used to synthesize ATP from ADP and Pi.
***This process of oxidative phosphorylation couples the energy from electron transport to the synthesis of ATP.
In the liver, hexoses ___ and ____ are converted to glucose, the primary energy source for muscle contractions, red blood cells, and the brain.
fructose and galactose
takes place in the cytosol of the cell.
is a metabolic pathway that uses glucose, a digestion product.
degrades six-carbon glucose molecules to three-carbon pyruvate molecules.
Glycolysis
where does glycolysis occur?
cytosol
Where do we see NAD in Glycolysis?
In reaction 6, oxidation and phosphorylation,
the aldehyde group of each glyceraldehyde-3-phosphate is oxidized to a carboxyl group.
NAD+ is reduced to NADH and H+.
a phosphate group is transferred to each of the new carboxyl groups, forming two molecules of 1,3-bisphosphoglycerate.
sometimes to regenerate the NAD needed for step 6 in glycolysis…. what is one mechanism our body can do this anaerobically?
Anaerobic metabolism of pyruvate into Lactate… this allows for NADH + H+ —-> NAD+
High levels of NADH activates
lactate dehydrogenase molecule to make lactate (out of pyruvate)
What is step 1 of glycolysis, i.e. ___ turns Glucose into ____
The enzyme hexokinase catalyzes the phosphorylation of glucose to glucose-6-phosphate (G6P)
Glycolysis is regulated by three enzymes…. name them
In reaction 1, hexokinase is inhibited by high levels of glucose-6-phosphate, which prevents the phosphorylation of glucose.
In reaction 3, phosphofructokinase, an allosteric enzyme, is inhibited by high levels of ATP and activated by high levels of ADP and AMP.
In reaction 10, pyruvate kinase, another allosteric enzyme, is inhibited by high levels of ATP or acetyl CoA.
In glycolysis, there is a net gain of
two ATPs and two NADHs.
In glycolysis, there is a net gain of
two ATPs and two NADHs.
In reaction 1, hexokinase is inhibited by high levels of ___ which prevents…
glucose-6-phosphate, which prevents the phosphorylation of glucose
In reaction 3, phosphofructokinase, an allosteric enzyme, is inhibited by ___ and activated by ____
inhibited by high levels of ATP and activated by high levels of ADP and AMP.
In reaction 10, pyruvate kinase, another allosteric enzyme, is inhibited by ___ or ___.
In reaction 10, pyruvate kinase, another allosteric enzyme, is inhibited by high levels of ATP or acetyl CoA.
GLYCOLYSIS finish the Rxn below from one glucose molecule:
Glucose + 2 NAD+ + 2 ADP + 2Pi —->
Glucose + 2 NAD+ + 2 ADP + 2Pi
—->
Pyruvate + 2 NADH + 2 ATP + 4H+ + 2H2O
glycogen synthase - synthesis
glycogen phosphorylase - break down
Glycogenesis: Rxn 3 remember that GLYCOGEN SYNTHASE catalyzes the breaking of the phosphate bond to glucose in UDP-glucose so glucose can be added to the glycogen chain
In glycogenolysis, glycogen is broken down to glucose.
• glucose molecules are phosphorylated by glycogen
phosphorylase
glycogen phosphorylase cleaves α(1 4)-links until only oneglucose remains bonded to the main chain.
In muscles and kidneys, fructose is phosphorylated to
_____, which enters glycolysis in
reaction 3.
fructose-6-phosphate
Galactose reacts with ATP to yield galactose-1-
phosphate, which is converted to ______,
which then enters glycolysis at reaction 2.
glucose-6-phosphate
Pathways for Pyruvate
aerobic conditions
anaerobic conditions
anaerobic - fermentation or lactate
- fermentation: pyruvate –> ethanal + CO2 –> Ethanol (don’t forget NADH + H+ helps ethanal become ethanol and makes NAD+)
- lactacte: pyruvate (NADH + H+ to NAD+) –> Lactate
aerobic - acetyl
Pyruvate —> HS-COA + Pyruvate + (NAD+ to NADH) —> Acetyl CoA + CO2 AKA Acetyl-S-CoA + CO2
Under aerobic conditions, oxygen is available to convert
pyruvate to
acetyl coenzyme A (acetyl CoA) and CO2.
When oxygen levels are low, pyruvate is reduced to
lactate.
Under aerobic conditions (oxygen present), pyruvate
moves from the __ to the ___
is oxidized when a carbon atom is removed as CO2 as….
cytosol into the mitochondria to be oxidized further.
…the coenzyme NAD+ is reduced.
under aerobic conditions… The resulting two-carbon acetyl group is attached to CoA, producing….
…acetyl CoA, an important intermediate in many metabolic pathways.
Under anaerobic conditions (without oxygen),
- pyruvate is reduced to lactate and NAD+ by ___.
- NAD+ is used to oxidize ____ in the glycolysis pathway, producing a small amount of ATP.
lactate dehydrogenase
glyceraldehyde-3-phosphate
produced during anaerobic conditions
lactate
B. reaction series that converts glucose to
glycolysis pyruvate
C. metabolic reactions that break down large molecules to smaller molecules + energy
catabolic reactions
D. substances that remove or add H atoms in oxidation and reduction reactions
coenzymes
Glycogenesis
- is the metabolic process of converting glucose molecules into glycogen.
- produces ___ in this step of glycolysis
glucose-6-phosphate in reaction 1 of glycolysis.
Glycogenesis
- is the metabolic process of converting glucose molecules into glycogen.
- produces ___ in this step of glycolysis
glucose-6-phosphate in reaction 1 of glycolysis.
activated by low levels of blood glucose
glycogenolysis
B. converts glucose-1-phosphate to glucose-6-phosphate
glycogenolysis
C. activated by high levels of glucose-6-phosphate
glycogenesis
D. glucose + UTP UDP-glucose + Ppi
glycogenesis
• is a polymer of glucose with α(1 4)-glycosidic bonds and multiple branches attached by α(1 6)-glycosidic
bonds.
Glycogen
is formed when high levels of glucose-6-phosphate are
formed in the first reaction of glycolysis.
Glycogen
is not formed when energy stores (glycogen) are full,
which means that additional glucose is converted to
triacylglycerols and stored as body fat
Glycogen
Glycogenesis
1) G6P
2) G1P
3) UDP-Glucose
4) Glycogen
What is the regulatory enzyme?
Glycogen synthase
–Activated by insulin
–Inhibited by glucagon (liver) and epi (muscle)
Glycogenesis rxn steps?
which step adds uridine?
1) G6P
2) G1P
3) UDP-Glucose
4) Glycogen
Step 2 going to step 3 releases energy with enzyme pyrophosphorylase to transfer high energy UTP adding UMP to G1P
Glycogenolysis: Reactions 1 and 2
______ cleaves α(1 4)-links until only one glucose remains bonded to the main chain.
glycogen phosphorylase
Glycogenolysis:
is also the regulatory enzyme?
Activated by?
Regulated by?
glycogen phosphorylase
Activated by glucagon (liver) and epic (muscle)
Regulated by insulin
what helps activate glycogen synthesis and is also added to the end of the glycogen chain
UTP or Uridine Tri Phosphate
To protect the brain, hormones with opposing actions control blood glucose levels such as
- glucagon,
- insulin,
- epinephrine.
Gluconeogenesis: Glucose Synthesis
Where?
For which organs use it as their main energy source?
Glucose is synthesized in the tissues of the liver and kidneys.
Tissues that use glucose as their main energy source are the brain, skeletal muscles, and red blood cells.
If our glycogen stores are depleted,
• liver cells synthesize glucose by gluconeogenesis.
• glucose is synthesized in the cytosol of the liver cells,
and some is synthesized in the kidneys.
To begin gluconeogenesis, carbon atoms from noncarbohydrate food sources are converted to
pyruvate.
To start the synthesis of glucose from pyruvate,
• two catalyzed reactions are needed to replace reaction
10 in glycolysis to bypass the irreversible rxn
pyruvate carboxylase uses the energy of ATP hydrolysis
to catalyze the addition of CO2 to pyruvate and produce
oxaloacetate.
• phosphoenolpyruvate carboxykinase converts
oxaloacetate to phosphoenolpyruvate.
• phosphoenolpyruvate molecules now use enzymes to
form fructose-1,6-bisphosphate.
Gluconeogenesis new steps as far as new names of enzymes
- Pyruvate Carboxylase
- Phosphoenolpyruvate carboxykinase
- Fructose 1, 6 Biphosphatase
- Glucose-6-Phosphate
The second irreversible reaction in glycolysis is bypassed when fructose-1,6-bisphosphatase cleaves a phosphate group from fructose-1,6-bisphosphate to continue step 9 of Gluconeogenesis
F 1,6 B to F6P
Gluconeogenesis
In the final irreversible reaction, the phosphate group of glucose-6-phosphate is hydrolyzed by a different enzyme, ______, to form glucose.
glucose-6-phosphatase
Energy Cost of Gluconeogenesis
• The pathway consists of seven reversible reactions of
glycolysis and four new reactions that replace the three
irreversible reactions.
• Overall, glucose synthesis requires four ATPs, two GTPs, and two NADHs.
what do you start and finish with in the Krebs cycle?
oxaloacetate
Tell me about the Krebs cycle or Citric Acid Cycle and I mean EVERYTHING
Which steps turn NAD to NADH+H?
Which steps make FADH2?
Which steps turn GTP in to ATP?
Acetyl CoA + O-CIASSFMO for products
CAIASSFM for enzymes
Remember we switched your cycle up to start with what you ended before Central is now preceded by Only and for enzymes Army is now preceded by Cookies!
NADH+H+ made in steps 3, 4, and 8
GTP turned to ATP in step 5
FADH2 made in step 6
- an acetyl group bonds with oxaloacetate to form citrate.
- two decarboxylations remove two carbons as two CO2.
- four oxidations provide hydrogen for three NADHs and one In the citric acid cycle, FADH2.
- a direct phosphorylation forms GTP (ATP).
In the citric acid cycle
what are the products of the citric acid cycle total?
CoA + 3NADH + 3H + FADH2 + GTP + 2CO2
Regulation of the Citric Acid Cycle
The reaction rate for the citric acid cycle
• increases when ____ activate isocitrate
dehydrogenase.
• decreases when high levels of __ or ___ inhibit citrate synthase (first step in cycle).
low levels of ATP
ATP or NADH
3 regulating enzymes of the citric acid cycle?
1) Citrate synthase
3) Isocitrate dehydrogenase
4) A-Ketoglutarate dehydrogenase
3 regulating enzymes of the citric acid cycle, what activates and down regulates each?
1) Citrate synthase
3) Isocitrate dehydrogenase
4) A-Ketoglutarate dehydrogenase
1) Citrate synthase
ADP activates
NADH, ATP, and Citrate down regulates
3) Isocitrate dehydrogenase
ADP activates
NADH and ATP down regulates
4) A-Ketoglutarate dehydrogenase
ADP activates
NADH and Succinyl CoA down regulates
Ho w many of each of the following are produced in one turn of the citric acid cycle?
A. _ CO2 B. _ NADH
C. _ FADH2 D. _ GTP
A. 2 CO2
B. 3 NADH
C. 1 FADH2
D. 1 GTP
Cytochrome c carries one electron when
Fe 3+ is reduced to Fe2+ (orange sphere).
Electron transport AKA
Occurring in the matrix between the inner and outer membrane of the mitochondria and stepping high energy molecules down. All of these are oxygen dependent!!
respiratory chain
Th e reduced coenzymes NADH and FADH2 produced from glycolysis, oxidation of pyruvate, and the citric acid cycle are
oxidized to provide the energy for the synthesis of ATP.
In electron transport or the respiratory chain,
• hydrogen ions and electrons from NADH and FADH2 are
passed from one electron acceptor or carrier to the next
until they combine with…
• energy released during electron transport is used to
synthesize ATP from ADP and Pi during ____
…oxygen to form H2O.
oxidative
phosphorylation.
How many ATP are made from Glycolysis, Citric Acid Cycle Results?
How about in terms of ATP and Reduced Coenzymes?
32 ATP total
Glycolysis: 2 ATP, 2 NADH
Oxidation of pyruvate: 2 NADH
Citric acid cycle w/ 2 acetyl-CoA: 2 ATP, 6NADH, 2 FADH2
when you add all these up you get 4 ATP, 10 NADH, and 2 FADH2 which adds up after converting to 32 TOTAL ATP!
what is citrate synthase?
In the first reaction of the citric acid cycle,
catalyzes the condensation of an acetyl group (2C) from acetyl CoA with oxaloacetate (4C) to yield
citrate (6C) and coenzyme A.
the energy to form citrate is provided by the hydrolysis of
the high-energy thioester bond in acetyl CoA.
what turns on and off the citric acid cycle for all intensive purposes?
citrate synthase
two electron carriers, ___ and ____, attached to the inner
membrane of the mitochondrion, carry
electrons among these protein complexes
bound to the inner membrane.
coenzyme Q (CoQ) and cytochrome c
in the ETS what’s being pumped across the membrane (not passed along but actually travels through)?
Protons (H+) travel through DUE to the electrons being transported down the chain
In electron transport, the oxidation of __ and___provides hydrogen ions and electrons that eventually react with oxygen to form water.
NADH and FADH2
electron transport begins when hydrogen ions and electrons are transferred from
NADH to complex I.
loss of hydrogen from NADH regenerates NAD + to oxidize more substrates in
oxidative pathways such as the citric acid cycle.
hydrogen ions and electrons are transferred
to the mobile electron carrier CoQ, forming
CoQH 2.
CoQH2 carries electrons from complexes I
and II to complex III.
Complex I
During electron transfer,
• H+ ions are pumped through complex I into the intermembrane space, producing a reservoir of H+ (hydrogen ion gradient).
for every two electrons that pass from NADH to CoQ,
4H+ are pumped across the mitochondrial membrane,
producing a charge separation on opposite sides of the
membrane.
All true
What allows FADH2 and NADH to be oxidized and return to the citric acid cycle?
The electron transport Chain or system
Complex II consists of the enzyme ____ from the citric acid cycle.
succinate dehydrogenase
In complex II,
• CoQ obtains hydrogen and electrons directly from
This produces CoQH2 and regenerates the oxidized
coenzyme….
FADH2.
….FAD, which becomes available to oxidize more substrates.
In complex II,
• CoQ obtains hydrogen and electrons directly from
FADH2 and becomes CoQH2.
• two electrons are transferred from the mobile carrier
CoQH2 to a series of iron-containing proteins called
cytochromes.
• electrons are then transferred to two cytochrome c,
which can move between complexes III and IV.
all true
- contains Fe3+/Fe2+, which is reduced to Fe2+ and oxidized to Fe3+.
- generates energy from electron transfer to pump 4H+ from the matrix into the intermembrane space, increasing the hydrogen ion gradient.
Cytochrome c
Energy is coupled with the production of ATP in a process called
oxidative phosphorylation.
chemiosmotic model
• links the energy from electron transport to a hydrogen
ion gradient that drives the synthesis of ATP.
• allows complexes I, III, and IV to act as hydrogen ion
pumps, producing a hydrogen ion gradient.
• equalizes pH and electrical charge between the matrix
and intermembrane space that occurs when H+ must
return to the matrix.
all true
In the chemiosmotic model,
• H+ cannot move through the inner membrane but returns to the matrix by passing through a fifth protein complex in the inner membrane called….
called ATP synthase (also called complex V).
• the flow of H+ from the intermembrane space through the ATP synthase generates energy that is used to synthesize
ATP from ADP and Pi.
This process of oxidative phosphorylation couples the energy from
electron transport to the synthesis of ATP.
What regulates electron transport?
- is regulated by the availability of ADP, Pi, oxygen (O2), and NADH.
- decreases with low levels of any of these compounds and decreases the formation of ATP.
What regulates electron transport?
- is regulated by the availability of ADP, Pi, oxygen (O2), and NADH.
- decreases with low levels of any of these compounds and decreases the formation of ATP.
When a cell is active and ATP is consumed rapidly, the elevated levels of ADP will
activate the synthesis of ATP.
The activity of electron transport is strongly dependent on the availability of
ADP for ATP synthesis.
Ma tch each with its function: CoQ cyt c
A. a mobile carrier between complexes II and III
B. carries electrons from complexes I and II to
complex III
C. accepts 2H+ and 2 electrons from FADH2
Match each with its function: CoQ cyt c
A. a mobile carrier between complexes II and III - cyt c
B. carries electrons from complexes I and II to
complex III - CoQ
C. accepts 2H+ and 2 electrons from FADH2 -
CoQ
- CO 2
A. citric acid cycle B. electron transport chain - FADH2
A. citric acid cycle B. electron transport chain - NAD+
A. citric acid cycle B. electron transport chain - NADH
A. citric acid cycle B. electron transport chain - H2O
A. citric acid cycle B. electron transport chain
- CO2 A. citric acid cycle
- FADH2 A. citric acid cycle
- NAD+ B. electron transport chain
- NADH A. citric acid cycle
- H2O B. electron transport chain
At complex IV,
- four electrons from four cytochrome c are passed to other electron carriers.
- electrons combine with….
- energy is used to pump H+ from the mitochondrial matrix into the intermembrane space, further increasing the hydrogen ion gradient.
….hydrogen ions and oxygen (O2) to form two molecules of water.
Look at table 23.1 again for ATP from Oxidation of Glucose
DO IT DUDE
The _____ transfers the energy stored in NADH to transporters that move from the cytosol into the mitochondrial matrix where NADH is regenerated for use in electron transport
malate–aspartate shuttle
catalyzes the reaction of
oxaloacetate and NADH to yield malate and NAD+.
malate dehydrogenase
a transporter binds the malate and carries it across the
membrane into the matrix, where malate dehydrogenase
oxidizes malate back to
oxaloacetate.
The oxidation to oxaloacetate provides hydrogen ions and electrons that are used to reduce NAD+ to NADH, which can now enter
electron transport to synthesize ATP.
Be cause the oxaloacetate produced in the matrix cannot cross the mitochondrial membrane, it
- is converted back to aspartate;
- moves out of the matrix back into the cytosol; and
• undergoes transamination, which converts it to
oxaloacetate.
The resulting NAD+ can participate again in glycolysis in the cytosol.
ALL TRUE
The complete oxidation of glucose to CO2 and H2O yields a maximum of
32 ATPs.
stores 85% of the total energy available in the body.
Adipose tissue (made of adipocytes)
What is the function of bile salts in fat digestion?
Bile salts break down fat globules, allowing pancreatic lipases to hydrolyze the triacylglycerol.
How is glycerol utilized?
Glycerol adds a phosphate and is oxidized to an intermediate of the glycolysis and gluconeogenesis pathways.
In the digestion of fats (triacylglycerols),
___break fat globules into smaller particles called micelles in the small intestine.
bile salts
In the digestion of fats (triacylglycerols),
____ hydrolyze ester bonds to form monoacylglycerols and fatty acids, which recombine in the intestinal lining.
pancreatic lipases
In the digestion of fats (triacylglycerols),
__ and ___ coat the fats, forming ____, which are transported to the cells of heart, muscle, and adipose tissues.
phospholipids and proteins
chylomicrons
In the digestion of fats (triacylglycerols),
lipases hydrolyze triacylglycerols, forming glycerol and free fatty acids, which are
oxidized to acetyl CoA molecules for ATP synthesis.
The digestion of fats begins in the small intestine when bile salts….
…emulsify fats that undergo hydrolysis to monoacylglycerols and fatty acids.
the hormones glucagon and epinephrine are secreted into the bloodstream, where they bind to receptors on the membrane of adipose tissue.
When blood glucose is depleted and glycogen stores are low
a hormone-sensitive lipase within the fat cells catalyzes the hydrolysis of triacylglycerols to glycerol and free fatty acids.
When blood glucose is depleted and glycogen stores are low,
glycerol and fatty acids diffuse into the bloodstream and bind with plasma proteins to be transported to the tissues, muscles, and fat cells.
When blood glucose is depleted and glycogen stores are low,
glycerol and fatty acids diffuse into the bloodstream and bind with plasma proteins to be transported to the tissues, muscles, and fat cells.
When blood glucose is depleted and glycogen stores are low,
Metabolism of Glycerol
from fat digestion
3 main points?
adds a phosphate from ATP to form glycerol-3-phosphate.
undergoes oxidation of the —OH group to dihydroxyacetone phosphate (thereby forming NADH + H as a byproduct)
becomes an intermediate in glycolysis and gluconeogenesis.
steps of glycerol metabolism
1) Glycerol to G3P (w/ ATP to ADP)
2) G3P to DHP (w/ NAD+ to NADH + H+)
3) DHP enters glycolysis or Gluconeogenesis
Where is glycerol converted to DHP?
What is the significance?
in the liver
it’s an intermediate for glycolysis and gluconeogenesis
A large amount of energy is obtained when fatty acids undergo
oxidation in the mitochondria to acetyl CoA.
A large amount of energy is obtained when fatty acids undergo what? How does this occur?
beta oxidation (β oxidation), which removes two-carbon segments containing the alpha and beta carbon from the carboxyl end of the fatty acid.
A cycle in β oxidation
produces
an acetyl CoA and a fatty acid that is shorter by two carbons.
A cycle in β oxidation repeats until the original fatty acid is
completely degraded to two-carbon units that form acetyl CoA, which enters the citric acid cycle.
where does Fatty acid activation occur?
it begins in the cytosol as fatty acids are transported into the inner mitochondrial membrane to undergo β oxidation
Fatty Acid Activation
a fatty acid is combined with CoA to yield
a high-energy fatty acyl CoA.
Fatty Acid Activation
energy is released by the hydrolysis of ATP to AMP and used to
drive the reaction.
fatty acid + ATP + CoA to yield Fatty acyl CoA + AMP + 2Pi + H2O
fatty acid + ATP + CoA to yield?
Fatty acyl CoA + AMP + 2Pi + H2O
A transport system called the ______ carries fatty acids into the mitochondria from the cytosol.
carnitine shuttle
Transport of Fatty Acyl CoA
________catalyzes the transfer of a fatty acyl group to the hydroxyl group of carnitine to produce fatty acyl carnitine.
_______ then passes through the inner mitochondrial membrane into the matrix.
Carnitine acyltransferase
Fatty acyl carnitine
Transport of Fatty Acyl CoA (continued):
In the matrix, another carnitine acyltransferase
catalyzes the reverse reaction that transfers the ___ to ___-
releases the carnitine and returns to the cytosol.
fatty acyl group to CoA to reform fatty acyl CoA.
Thus, the carnitine shuttle moves fatty acyl CoA from the cytosol into the matrix, where
the fatty acid can undergo β oxidation.
Look at ch 24 slide 15 to draw the carnitine shuttle system…
do IT!
Oxidation of Unsaturated Fatty Acids
What’s the significance?
No FADH2 produced in first cycle because we already have the double bond and they can skip oxidation step and go straight to hydration … therefore less energy!
How many acetyl CoA groups are produced by the complete β oxidation of palmitic acid (C16)?
1) 16 2) 8 3) 7
How many oxidation cycles are necessary to completely oxidize palmitic acid (C16)?
1) 16 2) 8 3) 7
How many acetyl CoA groups are produced by the complete β oxidation of palmitic acid (C16)?
2) 8 (16 C/2 = 8)
How many oxidation cycles are necessary to completely oxidize palmitic acid (C16)?
3) 7 (16 C/2 – 1 = 7)
Four steps of β oxidation simplified?
OHOC
1) Oxidation with enzyme Acyl CoA deydrogenase and FAD to FADH2 (C=C created)
2) Hydration with Enoyl CoA hydrase (H2O added so B carbon has OH
3) Oxidation with enzyme 3-Hydroxyacyl CoA dehydrogenase and NAD+ to NADH + H+ (to make a C=O bond)
4) Cleavage (β-Ketoacyl CoA thiolase to cleave off two carbons each time and creates Acetyl CoA each time from the Fatty acyl CoA)
Match the reactions of β oxidation with each of the following:
Water is added. FADH2 forms. A two-carbon unit is removed. A hydroxyl group is oxidized. NADH forms.
1) oxidation 1
2) hydration
3) oxidation 2
4) acetyl CoA cleaved
Match the reactions of β oxidation with each of the following:
Water is added. 2) hydration
FADH2 forms. 1) oxidation 1
A two-carbon unit is removed. 4) acetyl CoA cleaved
A hydroxyl group is oxidized. 3) oxidation 2
NADH forms. 3) oxidation 2
ATP from β Oxidation, Capric Acid?
10 carbon Fatty acid
Math is on page 29
Total of 64 ATP
What is the total ATP produced from the β oxidation of stearic acid (C18)?
A. 108 ATP
B. 120 ATP
C. 148 ATP
What is the total ATP produced from the β oxidation of stearic acid (C18)? B. 120 ATP Activation –2 ATP 9 Acetyl CoA × 10 ATP 90 ATP 8 NADH × 2.5 ATP 20 ATP 8 FADH2 × 1.5 ATP 12 ATP 120 ATP
What’s the difference between Type I and Type II diabetes?
Type 1, insulin-dependent diabetes - Little to NO insulin produced
In type 2, insulin-resistant diabetes - insuline produced but RECEPTORS aren’t responsive… WON’T RESPOND TO INSULIN THERAPY!!!
WHICH DIABETES TYPE WILL NOT RESPOND TO INSULIN THERAPY?!?
type 2, insulin-resistant diabetes - insuline produced but RECEPTORS aren’t responsive
Ketogenesis acronym?
Cons
Hate
Home
Depot
Condensation
Hydrolysis
Hydrogenation
Decarboxylation
2 questions from this section…. slow down turbo
If carbohydrates are not available,
fatty acids break down to meet energy needs.
acetyl CoA molecules combine to form ketone bodies.
When large quantities of fatty acids are degraded,
too much ____ is produced.
high levels of acetyl CoA accumulate in the ____.
acetyl CoA molecules combine in a pathway known as…
acetyl CoA
liver
…ketogenesis to form compounds called ketone bodies.
What is the reason for ketogenesis?
The oxidation of large amounts of fatty acids causes high levels of acetyl CoA which undergoes ketogenesis
In ketogenesis,
how many molecules of acetyl CoA combine to form acetoacetyl CoA and HS—CoA?
two molecules of acetyl CoA
combine to form acetoacetyl CoA and HS—CoA.
When the body has met all its energy needs AND the glycogen stores are full,
acetyl CoA from the breakdown of carbohydrates and fatty acids is used to synthesize….
two-carbon acetyl units are linked to form a ____, in the pathway called lipogenesis.
this whole thing is so we can do what?!?!?!
new fatty acids in the cytosol.
16-carbon fatty acid, palmitic acid
Fatty Acid Synthesis!!!!
Where does lipogenesis occur? (not a reversal of B oxidation)
using which coenzyme?
occurs in the cytosol using the reduced coenzyme NADPH instead of occurring in the mitochondria, where oxidation takes place using FAD and NAD+.
synthesis of fatty acids occurs where?
cytosol
what’s the first step we must do for us to undergo Fatty acid synthesis?
an acyl carrier protein (HS—ACP) activates the acyl compounds.
ACP attaches to your “acetyl CoA AKA “APP”)
Before fatty acid synthesis can begin, the _____ must be synthesized.
activated carriers
The synthesis of a three-carbon malonyl ACP requires?
the synthesis of malonyl CoA, when acetyl CoA combines with bicarbonate.
the hydrolysis of ATP, which provides the energy for the reaction.
So for every malonyl ACP that is added (to keep adding two carbons to our fat) we require what?
1 ATP
In reaction 2, reduction,
3-ketoacyl ACP reductase reduces the 3-keto group using
2H from NADPH + H+.
In the cytosol, what is used to provide hydrogen for reduction reactions?
NADPH
which two steps of fatty acid synthesis utilize NADPH + H for a reduction reaction?
steps 2 and 4
reduce the double bond to a single bond
What is transamination?
the transfer of an amino group to an Alpha-Keto acid
AA’s coverted into A-keto acids and glutamate
Where do we see transamination?
The degradation of proteins and amino acids
Transamination starts when the amount of amino acids needed for synthesis of nitrogen compounds is in excess
how do we create glutamate?
transamination of AA’s
how do we produce a-ketoglutarate?
the OXIDATIVE DEAMINATION of glutamate…. this produces a-ketoglutarate and ammonium ions
Match each with the description below.
1) Mitochondria 2) cytosol 3) glucagon
4) Insulin 5) acetyl ACP 6) malonyl ACP
A. site of fatty acid synthesis B. site of β oxidation C. starting material for lipogenesis D. compound added to elongate acyl ACP E. activates β oxidation F. activates lipogenesis
A. site of fatty acid synthesis B. site of β oxidation C. starting material for lipogenesis D. compound added to elongate acyl ACP E. activates β oxidation F. activates lipogenesis
2) Cytosol
1) mitochondria
5) acetyl ACP,
6) malonyl ACP
3) glucagon
4) insulin
what do we do with all of the ammonium ions created from oxidative deamination (which creates our a-ketoglutarate)?
they combine with CO2 and a phosphate group from ATP to form caramoyl phosphate
which is converted to ?
urea, which is excreted in?
urine
overall Degradation of Proteins is either from food or when?
When carbohydrates and lipids are not available
is completed in the small intestine by trypsin and chymotrypsin to form amino acids.
overall Degradation of Proteins
are used in the synthesis of nitrogen-containing compounds or degraded to urea and carbon skeletons that enter other metabolic pathways.
Proteins
Draw slide 65 protein turnover down on your whiteboard to understand the OVERALL BIG PIC
please
When dietary protein exceeds the nitrogen needed for protein synthesis, excess amino acids are degraded.
The α amino group is removed to yield an ____, which can be converted to an intermediate for other metabolic pathways.
α-keto acid
When dietary protein exceeds the nitrogen needed for protein synthesis, excess amino acids are degraded.
Carbon atoms from amino acids are used in the ___ as well as for synthesis of….
citric acid cycle as well as for the synthesis of fatty acids, ketone bodies, and glucose.
Most of the amino acids are converted to
urea
Most of the amino acids are converted to
urea
In a transamination reaction,
an α amino group is transferred from an amino acid to an α-keto acid, usually α-ketoglutarate.
what is produced?
a new amino acid and a new α-keto acid are produced.
In oxidative deamination,
the amino group —NH3+ in glutamate is removed as
what else is produced?
What is reduced?
an ammonium ion, NH4+.
α-ketoglutarate, which can enter transamination with an amino acid, is produced.
and NADH + H is produced from a reduction of NAD
The ammonium ion, the end product of amino acid degradation, is toxic if it is allowed to accumulate. How do we get rid of it?
The urea cycle converts ammonium ions to urea, which is transported to the kidneys to form urine.
Complete Oxidation of Glucose
ch 23 slide 47 IS IMPERATIVE to your grade… no joke
understand this and you will connect a lot of dots
Big picture of urea cycle 4 steps and what they requrie
Ammonium needs to be converted to urea
IN THE MITOCHONDRIAL MATRIX:
1) ammonium + CO2 + 2ATP allows the TRANSFER
IN THE CYTOSOL:
2) 2 more ATP plus a Condensation Rxn OR you can enter straight from ASPARTATE
3) CLEAVAGE to create Fumarate and Arginine
4) Arginine undergoes HYDROLYSIS to create UREA which is sent to the kidneys to create urine
4) HYDROLYSIS
overall equation for UREA
?
The overall reaction for urea formation from ammonia is as follows:
2 Ammonia + CO2 + 3ATP —> urea + water + 3 ADP
When you think Urea cycle think…
liver
and in the mitochondria AND cytosol
What is a ketone body?
the byproduct of ketogenesis:
acetoacetate, 3-hydroxybutyrate, and acetone
the process through which two carbon acetyl units link together to yield fatty acids
lipogenesis
the loss of ammonium ion when glutamate is degraded to a-ketoglutarate
oxidative deamination
slide 46 from Chapter 23 which is Table 23.1
KNOW ALL OF THIS AND YOU WILL GET PROBABLY 80% of the test questions for 23
the transfer of an amino group from an AA to an A-keto acid
transamination
Humans can synthesize 11 of the 20 amino acids found in their proteins.
TRUE
Nonessential amino acids are synthesized in the body, while essential amino acids must be obtained from diet.
TRUE
The α-keto acid carbon skeletons are obtained from the __ or ___ and converted to amino acids by….
citric acid cycle or glycolysis
…transamination
Nonessential amino acids are synthesized from intermediates of glycolysis and the citric acid cycle.
which are produced by transamination?
Nonessential amino acids such as alanine and aspartate are produced by transamination.
(both require Glutamate)
Alanine is made from PYRUVATE + Glutarate from glycolysis
Aspartate is made from oxaloacetate + glutamate which is in line with the CITRIC acid cycle
slide 97 ch 24
HUGE OVERVIEW OF METABOLISM GRAPHIC
Solid
OVER VIEW OF METABOLISM
the main components of a cell membrane
glycerophospholipids and sphingolipids
phospholipid composition:
nonpolar region:
hydrocarbon tail w/ two long-chain Fatty Acids
Polar Region:
Ionic” head” of phosphate and an ionized amino alcohol
Why does the lipid bilayer of phospholipids not fit closely together?
kinks of the carbon chains at the cis double bonds
NOT RIGID
some proteins on the outer surfac of the cell membrane are attached to carbs…. why?
these carb chains project into the surrounding fluid environment where they RECOGNIZE and COMMUNICATE with chemical messengers such as hormones and neurotransmitters
these reduce the flexibility of the lipid bilayer
cholesterol
what is the function of cholesterol in the cell membrane
adds strength and rigidity
two types of transport across cell membranes
active and passive
examples of passive transport
diffusion and facilitated diffusion
which molecules move through cell membrane via diffusion?
O2, CO2, urea, and water
which molecules move through cell membrane via facilitated diffusion?
Chloride ion, biarbonate ion, and glucose
active transport molecules:
against their gradient
K+, Na+, and Ca2+
The final electron receptor in ETC and what does it make?
complex IV and it makes water
ETC sets up proton gradient and what uses this?
ATP synthase via oxidative phosphorylation to bring back the protons (H+) into the inner mitochondrial to make ATP…. remember that he’s not asking how many hydrogens are getting pumped per complex etc
How many ATP from glycolysis?
7 ATP TOTAL: 2 ATP and 2 NADH (therefore 5 here from malate-aspartate shutting bringing them into mitochondria for ETC to total 7 ATP)
What does glycolysis end in ?
pyruvate
What is pyruvate turned into?
anaerobically –> ethanal to ethanol via fermentation OR
lactacte (skeletal muscle AND RBC’s according to Friday’s review, but not in the book)
aerobically –> acetyl CoA
name three things that require a lot of glucose to function properly?
Brain, skeletal muscle, and red blood cells
AA’s to review for nonessential
Alanine, aspartate, glutamine at least (he mentioned all three in Friday’s review)
3 major regulation points in glycolysis?
Reaction 1, 3, 10
Hexokinase
Phosphofructokinase
Pyruvate Kinase
What inhibits hexokinase?
high levels of G6P
What does phosphofructokinase catalyze?
Fructose-1,6-biphosphate which is inhibited by high levels of ATP and activated by high levels of ADP and AMP
what inhibits pyruvate kinase?
high levels of ATP or acetyl CoA which stops the formation of pyruvate in reaction 10 of glycolysis
name the molecule that inhibits hexokinase by feedback regulation in step 1 of glycolysis
G6P
what is the major control point for glycolysis?
phosphofructokinase
what must be done before beta oxidation?
activate the FA’s into “fatty acyl CoA” so it can be transmitted across the mitochondrial membrane via the carnitine shuttle for beta oxidation
Fatty acyl CoA + carnitine (with enzyme carnitine transferase_ to yield Fatty acyl carnitine + HS-CoA and then once inside the mitochondrial membrane?
back to Fatty acyl CoA so it can undergo Beta Oxidation
remember that unsaturated FA’s make less energy via Beta oxidation, because you’re entering into the cycle later
Unsaturated Fat = LESS energy
Gi = ?
inhibits cAMP and minor role in stim of phospholipase C
Gs = ?
cAMP production
via adenyl cyclase and protein kinase A signaling
Gq = ?
stimulates phospholipase c
G12/13 =
activation –> changes actin cytoskeleton and therefore reg of cell cycle and motility
Gt = ?
“transducin” molecules found in rods and cones
what are the second messengers molecules of the G proteins?
Adenyl cyclase (forms cyclic adenosine monophosphate)
Diacylglycerol (DAG) (cleaved from PIP)
Inositol triphosphate (IP3) (cleaved from PIP)
*Protein kinase C (changes membrane structure, regulate transcription/cell growth, assist in immune, provide key activation of proteins in learning/memory)
What are the first effectors and second effectors of the G proteins?
First effectors… external to the cell (e.g., ligand/hormone/neurotransmitters/etc.)
Second effectors… internal… trigger a cascade within the cell (e.g., release of cAMP, IP3, etc.)
____ catalyzes the condensation of an acetyl
group (2C) from acetyl CoA with oxaloacetate (4C) to yield
citrate (6C) and coenzyme A.
• the energy to form citrate is provided by the hydrolysis of
the high-energy thioester bond in acetyl CoA.
citrate synthase
Glycogen phosphorylase in Rxn 1 and 2 of what?
activated by?
inhibited by?
Glycogenolysis
activated by glucagon (liver) and epic (muscle)
inhibited by insulin
reminder 3000… less energy from an unsaturated fat in….
beta oxidation
PKU what is it and what causes it?
Phenylketonuria
A genetic disease is the result of a defective enzyme caused by a mutation in its genetic code. For example, phenylketonuria (PKU) results when DNA cannot direct the synthesis of the enzyme phenylalanine hydroxylase, required for the conversion of phenylalanine to tyrosine. In an attempt to break down the phenylalanine, other enzymes in the cells convert it to phenylpyruvate. If phenylalanine and phenylpyruvate accumulate in the blood of an infant, it can lead to severe brain damage and mental retardation. If PKU is detected in a newborn baby, a diet i s prescribed that eliminates all foods that contain phenylalanine. Preventing the buildup of phenylpyruvate ensures normal growth and development.
In the genetic disease phenylketonuria (PKU), a person cannot convert phenylalanine to tyrosine because the gene for the enzyme phenylalanine hydroxylase is defective. As a result, large amounts of phenylalanine accumulate. In this situation, a transaminase catalyzes the transfer of the –NH3+…
from phenylalanine to pyruvate to form alanine and phenylpyruvate, which is then decarboxylated to phenylacetate. Large amounts of these compounds are excreted in the urine. Phenylacetate has a characteristic odor in the urine that can be used to recognize PKU in infants.
what are the 5 membrane phospholipids (at least mentioned)
- Cardiolipin (Diphosphatidylglycerol)
- Phosphatidylserine (PS)—
- Phosphatidylethanolamine (PE)
- Phosphatidylcholine (PC)
- Phosphatidylinositol
What is cardiolipin?
Where is it found
– Negatively charged phospholipid with 4 FA
chains.
– Found in several locations, esp. inner mitochondrial membrane.
is important in in stabilizing the electron transport system of mitochondria.
Cardiolipin
Heart failure, diabetes, Alzheimer’s disease, and Parkinson’s disease all show changes of ____ composition of the mitrochondrial membrane.
cardiolipin
Trepenoma pallidum, the bacterilerum
responsible for the disease syphilis, produces
antibodies against
cardiolipin.
Major acidic phospholipid in brain (phosphate + carboxylate)
Phosphatidylserine (PS
Maintained on the cytosolic side and “flipped” by
flippase when needed for intercellular communication
(e.g. apoptosis).
Phosphatidylserine (PS)
Flipped to outer membrane of platelets during platelet
activation where it promotes thrombin formation
(coagulation); also served as a co-factor for the
anticoagulant protein C pathway, providing feedback
inhibition of thrombin formation.
Phosphatidylserine (PS)
Phosphatidylserine (PS) THINK…
platelets during platelet activation
AND
anticoagulant protein C pathway
Current research show effectiveness for ADHD,
memory loss, Alzheimer’s, and exercise-induced stress.
Phosphatidylserine (PS)
– Neutral/Zwitter ionic.
– Predominantly cytoplasmic side.
– 25% of all phospholipids.
Phosphatidylethanolamine (PE)
Regulates membrane curvature (small head
group/better packing).
Phosphatidylethanolamine (PE)
– More viscous than PC.
– Secreted in VLDL.
– Located in both the interior and exterior of cell membranes.
Phosphatidylethanolamine (PE)
Major compound of pulmonary surfactant
Phosphatidylcholine (PC)
used to calculate fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio.
Phosphatidylcholine (PC)
– Located on both sides of cell membrane, but usually > on exeterior.
– Promotes anticoagulant protein C pathway, but to
lesser degree than PS.
Phosphatidylcholine (PC
– Carries a negative charge.
– Located in the interior and exterior of cell membranes as well as the nuclear membrane.
Phosphatidylinositol
One isomer used exclusively in the gustatory (taste) modality nerves associated with sodium ion
sensitivity (“salty” channels).
Phosphatidylinositol
Phosphorylated version is PIP2 which can be cleaved
to form IP3 (an intracellular signal/2nd messenger).
Phosphatidylinositol
In general phospholipids with smaller head groups (e.g., PS and PE)
are preferred on the inner side of the membrane bilayer.
PS on the
outside of the bilayer can increase adherence to other cells and
tissues.
Phospholipid general info
A membrane-bound enzyme called flippase catalyzes the process of
moving particular phospholipid molecules from one side of the
bilayer to the other when required.
Phospholipid general info
Phospholipids with large head group size and charges, and double bonds in tail create a more fluid membrane more amenable to areas of cell curvature or cell.
Phospholipid general info
Proteins make up ~ 20%–80% of the structural & functional components
of membranes
TRUE
located predominately on one surface of the lipid bilayer.
Can act as anchor points for attachment to external structures (e.g., the extracellular matrix) and internal points.
Peripheral:
located within and/or across the width of membrane where hydrophobic AAs stay in hydrophobic environment of lipid bilayer. Integral proteins serve several functions including:
Integral:
channels, “carrier proteins” (trans- porting molecules through the membrane), or as signaling proteins.
Membrane proteins can contain
carbohydrates (glycoproteins).
Specific proteins and lipids can gather into specific regions of a biological membrane to perform specific functions such as cell signaling or transport
functions; specialized domains often form
lipid rafts.
____ are somewhat thicker and contain higher amounts of specialty lipids
(e.g., sphingomyelin, gangliosides, saturated phospholipids, and cholesterol).
Lipid rafts
Membrane proteins can also contain carbohydrates (i.e., glycoproteins) important
in membrane signaling.
What isa a primary function of biological membranes?
maintain separate chemical environments (diff concentrations of ions/molecules)
carbs cannot pass through easily… why?
cellular metabolism couldn’t be regulated & concentration gradients couldn’t be utilized
what moves through the lipid bilayer W/O specialized transport proteins?
O2, CO2, N2, and urea
what can move through the BBB?
ketone bodies
Membrane channels often have multiple α-helical
and/or
β-strand secondary structures that form tube- like channels through the membrane:
– Hydrophilic/charged AAs on inside of the channel; forms a suitable passageway.
– Hydrophobic AAs facing bilayer.
What type of channel is a gap junction? what does it allow?
A gap junction is a SIMPLE CHANNEL that creates a passageway in gap between two cells allowing movement of ions, sugars, amino acids, and nucleotides.
No energy is used & driven by a concentration gradient as well, but rate of
flow is sped up or slowed down based on conformational changes forming gated channels (facilitated diffusion).
Facilitated protein channels
Facilitated diffusion involving a carrier protein that undergoes a conformational change via the release of energy or phosphorylation from
nucleotide molecules.
Active transport
what is the point of the Na+ — K+ ATPase Pump and what type of transport?
what does it keep at the right level?
Active Transport Carrier protein that established Na outside the cell and K inside the cell
nerve impulses, muscle contraction, and to drive transport of carbs, AA’s, and nutrients into cells
keeps OSMOTIC PRESSURE at the right level
Know the three stages of stages of cells signaling
STAGES OF CELL SIGNALING:
RECEPTION, TRANSDUCTION, CELLULAR RESPONSE
Describe the four forms of cell signaling
- Paracrine signaling
- Autocrine signaling
- Endocrine signaling
- Signaling through cell-cell contact
can be defined as the target cell detection of signal molecule that is coming from outside of the cell.
Reception
can be defined as the target cell detection of signal molecule that is coming from outside of the cell.
Reception
The second stage of cell signaling is when the binding of signal molecule triggers the receptor protein of the target cell, initiating the process of _____.
Transduction:
The second stage of cell signaling is when the binding of signal molecule triggers the receptor protein of the target cell, initiating the process of _____.
Transduction:
The third stage of cell signaling is when the transduced signal triggers a specific cellular response such as modification of a cellular enzyme, rearrangement of the cytoskeleton, or activation of specific genes in the nucleus.
Response:
3 stages of cell signaling?
Ready To Rock
Reception
Transduction
Response
3 stages of cell signaling?
Ready To Rock
Reception
Transduction
Response
3 stages of cell signaling?
Ready To Rock
Reception
Transduction
Response
The signaling molecule behaves as a _____ that generally causes a receptor protein to undergo a conformational change and causes the aggregation of two or more receptor molecules, which leads to further molecular events inside the cell.
ligand
Reception 1 word description?
Transduction 1 word descriptions?
Response 1 word descriptions?
reception = detection
transduction = triggering ( or binding)
response = modification / rearrangement / activation
Four Forms of Cell Signaling
- Paracrine signaling
- Autocrine signaling
- Endocrine signaling
- Signaling through cell-cell contact
Cells that are near one another communicating through the release of signal molecules that can diffuse through the space between nearby cells.
Paracrine signaling
Paracrine signaling allows?
Paracrine signaling allows cells to locally coordinate activities with their neighbors.
Examples of paracrine?
Examples: • Coordination of cellular identities during spinal cord development.
• Synaptic signaling, in which nerve cells transmit signals between two nerve cells.
1 word description of paracrine?
coordination
• Cell signals to itself, releasing a ligand that binds to receptors on its own surface or to receptors inside of the cell.
Autocrine signaling
Helps cells take on and reinforce their
identities during development.
Autocrine signaling
May play a key role in the spread of cancer.
Autocrine signaling
Can have both autocrine and paracrine
effects, binding to the sending cell as well
as other similar cells in the area. ]
Autocrine signaling
1 word descriptions of autocrine?
itself
reinforce
cancer
paracrine (effects sometimes)
Signals consist of Hormones that are produced in
one part of the body and travel through the
circulation to reach targets throughout the body.
Endocrine signaling
The major Endocrine glands are the thyroid gland
and adrenal gland. Also includes the pituitary,
gonads, hypothalamus, and pancreas. Each
endocrine gland releases one or more types of
hormones.
Examples?
For example, the pituitary releases growth
hormone (GH), which promotes growth of the skeleton and cartilage.
Gap junctions are tiny water-filled channels that directly connect neighboring cells allowing small signaling molecules called ___ ____, to diffuse between the two cells.
intracellular mediators
These ____ that diffuse between ____ transmit the current state of one cell to its neighbor allowing a group of cells to coordinate their response to a signal that only one of them may have received.
signaling molecules that diffuse between gap junctions
Form of direct signaling where two cells may bind to one another because
they carry complementary proteins on their surfaces.
This interaction changes the shape of one or both proteins, transmitting a signal.
Cell to Cell Protein Receptor Interactions
This kind of signaling is especially important in the immune system, where
immune cells use cell-surface markers to distinguish between the body’s
own cells and cells infected by pathogens.
Cell to Cell Protein Receptor Interactions
Cell to Cell Protein Receptor Interactions… seen where in body?
immune system especially
– Signal passes through membrane by diffusion.
– Binds intercellular target.
Group I intracellular receptor proteins
Integral membrane protein that does not form a
channel or physically move through the membrane but, instead, transmits a message (signal) from one side of the lipid bilayer to the other.
Group II cell surface receptors
transmits a message (signal) from one side of the lipid bilayer to the other.
Group II cell surface receptors
Signal passes through membrane by diffusion.
Group I intracellular receptor proteins
Signal passes through membrane by diffusion
Binds intercellular target
Group 1: Intracellular Receptor Proteins
LOOK AT IMAGE ON SLIDE 33 of Cell signaling
Group 1 intracellular receptors what are the two examples from the table?
what about the 3rd intracellular receptor (not mentioned as group 1)?
Ligand Types:
Cholesterol Derived hormones
Small, hydrophobic signaling molecules
Ion channels (not mentioned as group 1), but still intracellular
Ligand Types:
Cholesterol Derived hormones
What are the hormone examples and their activity?
steroids - androgens (testosterone), estrogens, glucocorticoids (cortisol), mineralocorticoids (aldosterone), progesterone; non steroid - Vitamin D3
Activity - bind internal transcription factors / initiates DNA synthesis
Ligand Types:
Small, hydrophobic signaling molecules
What are the hormone examples and their activity?
Retinoic acid, thyroxine (T4), T3
activity - bind to protein factors that initiate synthesis of specific genes; ↑ various metabolic functions
Integral membrane protein transmits a message (signal)
from one side of the lipid bilayer to the other.
Group II cell surface receptors
– Upon external binding of
effector molecule, change conformation, phosphorylate of one of its AAs, and/or interacts w/ other proteins.
– Conformational change on the
external side changes internal side leading to downstream effects and turning on of second messengers.
Group II cell surface receptors
INTRA-cellular signaling VS INTER-cellular signaling
within itself vs to another cell
Look at the tables on pages 36 and 37 of the CELL SURFACE RECEPTORS examples includes the following
Gs, Gi, Gq, G13, TKJKA, integral guanyl cyclase activity
integral guanyl cyclase activity
ANP - increased cGMP (guanyl cyclase)
soluble receptor Tyrosine kinase (eg Janus kinase) activity
GH, leptin, prolactin, many cytokines (interferon-γ)
Activity - autophosphorylation –> transcription
integral receptor tyrosine kinase (G13) AKA Group IIC
Examples?
activity?
INSULIN
ISULIN-LIKE GROWTH FACTOR I
Activity - autophosphorylation –> activation of signal pathways
____ are lipid soluble and can
pass easily through the cell
membrane without the aid of a
membrane receptor.
Steroids
because steroids are lipid soluble… where you find most of their receptors?
IN THE CELL - Intracellular Steroid Receptors
Inside the cell, hormone
(a) binds with ___ _____ to activate signaling or
(b) may continue to receptors in the
nucleus to….
cytoplasmic receptors
…activate transcription
factors and DNA synthesis.
Steroid hormones that affect DNA synthesis are called
genomic (i.e., affect genes),
Steroid hormones that do not affect
transcription are referred to as
nongenomic. (don’t affect genes)
One of the most predominant and best understood membrane signaling mechanisms is via the G- protein family AKA
seven-
transmembrane domain
receptors
All G-protein receptors rely on
conformational change
resulting from the conversion
of
GDP –> GTP to convey an
external signal to the inside of
the cell.
G-proteins are all composed of three internal peripheral
protein subunits
α-, β-, and γ-subunits
associate with an integral membrane protein receptor.
α-, β-, and γ-subunits (three internal peripheral proteins)
of G-proteins
β- and γ-subunits are closely bound and are represented as
the dimer β/γ.
G-proteins can be divided into five classes
Gs, Gi, Gq, G12/13,
and Gt
G-proteins can be divided into five classes depending on differences in…
which effects interaction w/ ?
depending on differences in the α-subunit
which effects interaction w/ the external signaling molecule
cAMP production via adenyl cyclase and protein kinase A signaling (multiple targets)
Gs
Inhibits cAMP production; minor role in stimulation of phospholipase C
Gi
Stimulates phospholipase C
Gq
Activation leads to changes in the actin cytoskeleton and, therefore, regulation of cell cycle and motility
G12/13
“Transducin” molecules found in rods and cones couple visual signals between rhodopsin and cGMP phosphodiesterase
Gt
__ + ____ on cellular side associates with β/γ-subunits.
α-subunit + GDP
Binding of signal on exterior of the receptor –> conformational change.
True in mechanism of G-protein signaling
mechanism of G-protein signaling :
Free α-subunit can then interact with other ______
leading to?
membrane-bound proteins
(effectors),
leading to activation (Gs,Gq,G12/13, and Gt) or inhibition (Gi).
• α-subunit’s inherent GTPase activity eventually converts GTP → GDP,
allowing
α-subunit to reassociate with the β/γ-subunits → turning activation off.
• The various G-proteins activate several important membrane proteins
leading to
conveyance of the signal via second messenger molecules.
Cyclic Adenosine Monophosphate (cAMP):
Activation of __ ____ by the α-subunit results in the
conversion ATP → cAMP
which activates ___ ___ _
which phosphorylates various signaling proteins → cell response/expression of specific genes.
adenylyl cyclase
protein kinase A
Stimulatory ligands activate via Gs proteins, whereas
inhibitory ligands act via Gi proteins.
Cyclic Adenosine Monophosphate (cAMP)
(cAMP)
Cyclic Adenosine Monophosphate
Activation of phospholipase C (via the α-
subunit of G q) results in
the cleavage of
the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol
(DAG) and inositol triphosphate (IP3).
Basically PIP2 into DAG and IP3
Phospholipase C—Protein Kinase C (PKC) Signaling:
Hydrophilic IP3 leaves membrane and
enters the cytoplasm to
release Ca2+ from Endoplasmic Reticulum (ER).
Phospholipase C—Protein Kinase C (PKC) Signaling:
Ca2+ subsequently activates Ca2+ binding proteins (CaBP) → ?
Ca2+ subsequently activates Ca2+ binding proteins (CaBP) → activation of enzymes
and/or expression of specific gene products.
Phospholipase C—Protein Kinase C (PKC) Signaling:
Hydrophobic DAG remains in the membrane and can activate Protein Kinase C (PKC)
leading to
separate phosphorylation of proteins and resulting physiological effects (Ca2+
is also required to synergistically maximize this effect of DAG on PKC).
Activated G-Protein coupled receptors release
second messengers
second messengers:
– adenyl cyclase (AKA adenylyl or adenylate cyclase) forms cyclic adenosine
monophosphate (cAMP) resulting in phosphorylation of other molecules by protein kinase A.
– Diacylglycerol (DAG) and inositol triphosphate (IP3) by the action of
phospholipase C cleaving the membrane lipid phosphatidylinositol 4,5- bisphosphate (PIP) → intracellular release of Ca2+.
– Protein kinase C is known to change membrane structure, regulate
transcription and cell growth, assist in immune responses, and provide key activation of proteins involved in learning and memory.
_____ → multiple membrane, cytoplasmic, and nuclear effects
(e.g., muscle contraction, secretion of neurotransmitters, regulation of transcription factors, modulation of carbohydrate storage or use, etc.)
2nd messengers
Multistep signaling allows for selected amplification of a small signal at
the exterior of the cell membrane into a potentially large response within the cell.
Second Messengers
I.e. cAMP
_____ relies on
voltage-dependent calcium
channels (VDCCs).
Muscle contraction
Voltage-Dependant Calcium Channels:
Predominant cardiac VDCC =
L-type channel = pore-forming
α1 subunit w/ 6 trans-membrane
α-helices that opens/closes upon
voltage changes.
Voltage-Dependant Calcium Channels:
• β-subunit is a guanylate kinase that catalyzes ATP + GMP → ADP + GDP.
• Conversion of GMP to GDP regulates α1-pore voltage sensitivity (i.e.,
β-subunit activity allows smaller depolarizations and channel
opening)
• As action potential propagates, VDCCs open by….
depolarization of the cell membrane.
Adrenergic Receptors?
α1-adrenergic = Gq protein
(stimulates phospholipase C
pathway and ↑ Ca2+).
• α2-adrenergic = Gi protein (inhibits
adenylyl cyclase/cAMP pathway).
• β1 and β2-adrenergic = Gs protein
(stimulates adenylyl cyclase/cAMP
pathway).
α1-adrenergic =
Gq protein
(stimulates phospholipase C
pathway and ↑ Ca2+).
• α2-adrenergic =
Gi protein (inhibits adenylyl cyclase/cAMP pathway).
• β1 and β2-adrenergic =
Gs protein
(stimulates adenylyl cyclase/cAMP
pathway).
Epinephrine binds α1-, α2-, β1 and β2-adrenergic receptors (G- protein-coupled proteins) throughout body, but the heart has mainly
β1-receptors.
**[Note: β1 is dominant androgenic receptor in ____]
heart
β1 main location?
stimulation
blocking
heart & kidneys
stimulation effect:
↑ rate & force of contraction; ↑ renin
blocking effect:
↓ rate & force of contraction; ↓ renin
β2 main location?
stimulation
blocking
Lungs, GI, liver,
uterus, vascular & skeletal SM
stimulation effect:
SM relaxation of uterus , GI tract, bronchi and dilation of blood certain blood vessels to support flight or fight, ↑ breakdown of glycogen
blocking effect:
Block stimulatory effect of Nor/Epi, general dilation of blood vessels, ↓ BP
β3 main location?
stimulation
blocking
fat cells
stimulation effect:
↑ lipolysis
blocking effect:
No adrenergic-induced lipolysis increase
Gs is activated by adrenaline (stimulatory)
Read through this pathway in particular
seven-
transmembrane domain
receptors
G proteins coupled receptors (GPCRs)
which part of g-protein attaches to lipid membrane?
alpha and gamma…. beta is just attached to gamma
point of a g-protein?
binds GTP or GDP
where does GDP bind?
alpha subunit of g-protein
G-protein coupled receptors
Step 1: ligand attaches
Step 2: after ligand attaches to GPCR what happens
step 3?
step 4?
step 5?
step 6?
step 2? one of the seven alpha helices of the GCPR will undergo a conformation change
step 3: alpha subunit exchanges GDP for GTP
step 4: alpha subunit dissociates and regulates target protein (beta subunit can do this as well)
step 5: target protein relays signal via second messenger
step 6: GTP hydrolyzed to GDP (back to start and “ready”)
The signaling molecule (ligand) = epinephrine
GPCR = Adrenergic receptor (undergoes conformational change causing GDP to GTP on alpha subunit)
this causes what?
Alpha subunit seeks out another protein called…
…adenylate cyclase
adyenylate cyclase is now stimulated causing…
… ATP to produce cAMP (2 phosphates from ATP to create cAMP)
… cAMP is our “2nd messenger” and a new signal which….
goes to cells causing increase in HR, dilate blood vessels, breakdown glycogen to glucose (for more fight or flight)
GPCRs are what?
cell surface receptors
phosphorylation:
The transfer of the phosphate group is catalyzed by an enzyme called a
kinase
To flip proteins back into their non-phosphorylated state, cells have enzymes called ____, which remove a phosphate group from their targets.
phosphatases
Although proteins are important in signal transduction pathways, other types of molecules can participate as well.
Many pathways involve second messengers, small, non-protein molecules that pass along a signal initiated by the binding of a
ligand (the “first messenger”) to its receptor.
Second messengers include
Ca 2 +, cyclic AMP (cAMP), a derivative of ATP; and inositol phosphates, which are made from phospholipids.
In response to signals, an enzyme called ______ converts ATP into cAMP, removing two phosphates and linking the remaining phosphate to the sugar in a ring shape.
adenylyl cyclase
Once generated, cAMP can activate an enzyme called _____, enabling it to phosphorylate its targets and pass along the signal.
protein kinase A (PKA)
Inositol phosphates
Although we usually think of plasma membrane phospholipids as structural components of the cell, they can also be important participants in signaling. Phospholipids called _____ can be phosphorylated and snipped in half, releasing two fragments that both act as second messengers.
phosphatidylinositols
One lipid in this group that’s particularly important in signaling is called PIP2.
In response to a signal, an enzyme called phospholipase C cleaves (chops) PIP2 into two fragments, DAG and IP3
These fragments made can both act as
second messengers.
DAG stays in the plasma membrane and can activate a target called
protein kinase C (PKC), allowing it to phosphorylate its own targets.
___ diffuses into the cytoplasm and can bind to ligand-gated calcium channels in the endoplasmic reticulum, releasing ___ that continues the signal cascade.
IP3
Ca2+
Membrane phospholipids?
C4P
glucose + UTP –> UDP-glucose + Ppi
glycogenesis
Uridine Triphosphate used in what?
glycogenesis
What does epinephrine do differently between the liver and skeletal muscle?
How about adipose tissue and skeletal muscle?
epi increases glycolysis in skeletal muscle, but decreases it in the liver
epi increases TAG uptake from lipoproteins in skeletal muscle, but decreases it in adipose tissue
What is the last reaction of the citric acid cycle?
Reaction 8: Oxidation
In reaction 8, catalyzed by malate dehydrogenase,
• the hydroxyl group in malate is oxidized to a carbonyl group, yielding oxaloacetate.
• oxidation provides hydrogen ions and electrons for the
reduction of NAD+ to NADH and H+.
How does NADH get from cytosol into mitochondria?
The malate–aspartate shuttle transfers the energy stored in NADH to transporters that move from the cytosol into the mitochondrial matrix where NADH is regenerated for use in electron transport
How do you activate fatty acids?
Fatty acids in the cytosol are transported through the inner mitochondrial membrane to undergo β oxidation in the matrix.
In an activation process,
- a fatty acid is combined with CoA to yield a high-energy fatty acyl CoA.
- energy is released by the hydrolysis of ATP to AMP and used to drive the reaction.
Transport of Fatty Acyl CoA?
A transport system called the carnitine shuttle carries fatty acids into the mitochondria from the cytosol.
• Carnitine acyltransferase catalyzes the transfer of a fatty
acyl group to the hydroxyl group of carnitine to produce
fatty acyl carnitine.
• Fatty acyl carnitine then passes through the inner
mitochondrial membrane into the matrix.
Which AA’s are in the urea cycle?
aspartate in RXN 2
Fumarate leaves in RXN 3
Arginine in RXN 3 to 4
Th e ammonium ion, the end product of amino acid degradation, is toxic if it is allowed to accumulate. The ur ea cycle converts ammonium ions to urea, which is transported to the
kidneys to form urine.
Where do Rxn’s take place in urea cycle?
Rxn 1 in mitochondrial matrix… all others2, 3, 4 are in the cytosol
In a transamination reaction,
aspartate transaminase (AST)
catalyzes the reversible transfer of
an amino group between
glutamate and aspartate.
In a transamination reaction,
an α-amino group is transferred
from an amino acid to an
α-keto acid, usually α-ketoglutarate.
RBC’s have to get ATP from?
lactate which is why glycolysis is anaerobic
In the first step of fatty acid synthesis, an ACP-activated acyl group (malonyl ACP) is combined with
an ACP-activated acetyl group (acetyl ACP).
These two molecules must be synthesized before the first step of fatty acid synthesis can occur.
acetyl ACP and malonyl ACP
The synthesis of the three-carbon malonyl ACP first requires the synthesis of malonyl CoA, which occurs when acety 1 CoA combines with
The hydrolysis of ATP provides the energy for the reaction.
bicarbonate
Once malonyl CoA has been synthesized, it can be activated for fatty acid synthesis through addition to
HS-ACP.
An acetyl CoA group can be activated for fatty acid synthesis in a similar manner.
In fatty acid synthesis (lipogenesis), two-carbon units from acetyl CoA are added together to form palmitate.
The overall equation for the synthesis of palmitate from acetyl CoA is written as:
8 Acetyl CoA + 14NADPH + 14H+ + 7ATP –>
palmitate + 14NADP+ + 8HS-CoA + 7ADP + 7Pi + 6H2O
Where does B Oxidation occur?
How about Lipogenesis (Fatty Acid Synthesis)?
Mitochondrial matrix (activated by glucagon and low blood glucose via activator Coenzyme A)
Cytosol (activated by Insulin and High Blood Glucose via activator Acyl carrier protein)
catalyze the transfer of an amino group from one substrate to another
transaminases
What does alanine transaminase do ?
Alanine + A-ketoglutarate –> or
Remember that malate and aspartate can get into the mitochondria, but oxaloacetate must use…
aspartate transaminase
Because the oxaloacetate produced in the matrix cannot cross the inner mitochondrial membrane, it is converted back to aspartate by aspartate transaminase so it can move out of the matrix back into the cytosol, where
transamination converts it back to oxaloacetate.
In a process called oxidative deamination, the amino group (-NH3 +) in _____ is removed as an ammonium ion, NH4
glutamate
Through _____, the amino group from any amino acid can be used to form glutamate, which undergoes oxidative deamination, converting the amino group to an ammonium ion.
transamination
glutamate and aspartate is the transfer of an amino group and reversible via the catalyst
aspartate transaminase (AST)
What are the three ketone bodies produced from keto genesis
Either:
Acetoacetate creating beta-hydroxybutyrate
OR
Acetoacetate creating acetone
beta-hydroxybutyrate
acetone
Acetoacetate
