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Fundamentals
9/11/08
Dr. Pitchard
10:00-11:00
Integration of Metabolism
Today we are going to be talking about integration of metabolism. Last several weeks,
you have been learning all sorts of different biochemical pathways and conversations of
compounds. We teach these pathways separately, because it’s the only way you to do it.
One thing that gets lost is that, these reactions and pathways are going on at the same
time and in the same place. It’s the same concentration of ATP that affects that one
pathway, that also affects another pathway. Hopefully, you will get that message before
the lecture is over.
Slide 1 and 2 Integration of Metabolism
 This is a chart of intermediately metabolism. It looks really complicated but you
already know most of this already. You see these sugar metabolism, I covered. If
you remember what I talked about, this is all of it (sugar metabolism).
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Lipid Metabolism and Amino Metabolism is what Dr. Baggot talked bout.
Nucleotide metabolism.
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If you look at this chart, and what you have down the center. See what ties all
these metabolic pathways together is…..
Here’s Glycolysis, here is pyruvate right here, here is acetyl coA, citric acid cycle,
electron transport chain, urea cycle over here.
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Slide 3- Lines and Dot Figure
 The same chart, if every compound on chart and replace with a dot, you get
something like this (chart 2/ slide 2). This is kind of instructive because it shows
you how these things are interconnected.
 If you look at this, you see every one of these dots is compounds, and every line
connecting them is an enzyme.
 The interesting thing is, if you look at this, most of the compounds are just
intermediates on their way to making something else.
Slide 4- Lines and Dot Figure 2
Ctd from last slide.. Refer to figure
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These are connected by two lines. See here, most things are connected to one or
two lines. If it is one line like here, this would be an end product of a reaction or
starting material.
But most things are just on the pathway to make something else.
The interesting part of this is that some compounds are branch points that can go
always kinds of different ways.
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o Here’s pyruvate. Look at all the lines that are coming out of pyruvate.
o That means pyruvate can be used to make all kinds of different things.
o Or other things are being broken down that end up creating pyruvate.
There’s also acetyl CoA. It’s the same thing.
Up here we have glucose that goes to glucose-6-phosphate. Glucose-6-phosphate
can be used in Glycolysis, pentose phosphate pathway and to make glycogen.
It’s these points that can go multiple different ways that must be regulated.
The ways they go depends on the need of the cell.
Slide 5- Figure
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All these different reactions, I want you to remind of one thing- they occur
fundamentally different ways.
You have the studied different ways.
There are some enzymes that are soluble enzymes that are just in the cytoplasm
and the reactions that they catalyze the substrate will just diffuse and contact the
enzyme. It will be converted into something else. Then this new product will
come in contact with another enzyme and so on.
o There are many enzymes in the cell that are like that.
Other enzymes form multi-enzyme complexes. One you might remember is
pyruvate dehydrogenase. Remember this is big complex with loads of different (3
different) enzymes and multiple copies of them.
o What happens then is that when the substrate comes in, and it’s not
disassociated yet, it gets activated by on by one enzyme and moves to
another enzyme and so on before the product is released. That’s the multienzyme complex.
There’s another version of the multi-enzyme complex that is in the membrane of the cell.
The receptor comes here and gets converted here sequentially and then gets released.
Slid 6 Figure Catabolism and Anabolism
 So people as you know like to divide metabolism in to anabolism (where you
make things) and catabolism.
 Catabolis is where you break down large molecules and end up with very small
molecules. These are so-called high energy compounds like carbohydrates and
fats and proteins.
 So, anabolism is where you start with relatively simple compounds and make
large molecules.
 These different pathways (anabolism and catabolism) are interconnected by using
common products.
o For example, The ATP that is produced by catabolism can be used to
make things in anabolism or reducing activity produced in the pentose
phosphate pathway.
o From the oxidation of glucose can be used to make all different types of
molecules like fat as an example.
Slide 7- 3 Stages of Catabolism
**In this slide he was all over the place- he was breaking his sentences, so I did not
write down word for word. I just combined it in way that made sense.
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The purpose of this slide is to show you that when you breakdown complicated
molecules like proteins, lipids, polysaccharides, you will know these pathways of
breaking down.
Remember with polysaccharides, you break them down to monosaccharides and
pass it into the Glycolysis and to make pyruvate. You can break amino acids
(proteins) and make pyruvate. You can also get pyruvate from lipids and betaoxidation of fat will produce acetyl coA.
The point is that regardless of what you are starting with when you break these
things down, you break them down to common intermediates like acetyl coA.
Which can then be processed by citric acid cyle or other methods.
But the fact is that, you break all these compounds to the same small molecules.
Slide 8- Metabolic/ Catabolic Pathways
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These reason we can draw metabolic chart like that is that these pathways are
conserved.
Most of these pathways that we are discussing that occur in people, dogs, cats,
mushrooms, pine tree, etc.. these methods are very similar except in bacteria.
But, generally most these pathways are highly conserved.
I want to point out that catabolism involves oxidation and generally produces
ATP.
Catabolism involves reductions ----he didn’t finish this…. (*however I believe
this incorrect. because he just said that catabolism is in oxidation)
Slide 9- Pathways Continued
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Let’s see – I went over this before. The idea this that pathways can go both
forward or backward.
But in order to regulate them, there has to be one step that is different in the
pathway that makes something compared to the pathways that breaks something
down.
*****He mumbled a lot in this section along with cutting off thoughts/sentences. I
am thinking he couldn’t get whatever he had to say across.**** I would look the
slide in the powerpoint. *
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Notice here that these oxidative reaction of catabolism. They talk about producing
equivalence. They talk about hydride ions. Hydride ions- it’s not really not a
hydride ion.
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The point is that you are not really making H- ion.
If you look here, this reduction -you generate an H+.
Well, you get this compound.
What have you added to make this NADH? You have essentially added H-.
This H- is not really in solution, it’s not real….
People like to talk about hydride ions, what it is really is if it was H- when you
make the NADH.
Slide 10- NAD+/NADP+
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NAD/NADP, we have talked about this before especially PPP lecture. What
happens when you reduce these compounds, you convert this Niacin or
Nictoamide into this compound.
You remember this it’s the lack of this compound that results in pellagra. It’s
important molecule.
Slide 11 and 12- Alcohol Dehydrogenase Reaction
 Now, this is a theme I mentioned before, but if we drink beer wine or other
alcoholic beverages, your body oxidizes it. And in the process of oxidizing it,
NAD is used to oxidize the alcohol and is converted to NADH.
 You sequentially break down acetylaldehyde into acetyl coA and carbon dioxide.
 Here’s a question: How vigorous exercise influence the rate of breakdown of
ingested alcohol?
o For a long time, people you used to say that people who drank too much
can work it off (alcohol). Well, question does that do you any good?
o Remember what happens when you exercise vigorously, you are going
end up doing anaerobic glycolsis.
o You do anaerobic Glycolysis in the first place is because you are running
out of NAD. You have regenerate it.
o You regenerate by reducing pyruvate to lactate acid.
o You keep a level of NAD high enough so that you can use it in Glycolysis
to make more ATP.
 So if you are drinking alcohol, and you are using NAD to oxidize
the alcohol. Exercise vigorously, the alcohol is going stay around
longer.
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In 1960-1970 at UCLA, Krebs (the guy who figured out the krebs cycle), he have
a talk on alcohol and exercise. They put volunteers on treadmills and gave them
alcoholic beverages and measured how long it took the alcohol for it to be used
up. If you exercise vigorously, the alcohol hardly gets metabolized at all.
Slide 13- Regulation Figure
 Here again, is a message that I talked about before and other lecturers have.
 When you have these pathways that can break something down to a certain
product or make it again depending on what the cell needs, there are certain steps
that are regulated. That step is usually the first step in the path to make something.
 You see if the goal is to turn A into P, the first step will tend to be allosterically
regulated positively.
 At the same time, the reverse pathway will be allosterically regulated negatively.
People have observed this over and over in many different pathways.
Slide 14- 10 Catabolic Intermediates
In metabolism, interestingly there is only 10 small molecules that are used to make
almost everything. Few exceptions, but it’s usually a small number.
Slide 15- ATP has two metabolic Roles
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They like to say that ATP has two major roles. One role (we talk about a lot), it is
an allosteric effector. Affects all sorts of reaction by binding to the enzyme either
activating or inhibiting it.
It’s also important for forcing reactions to go in directions that it wouldn’t
normally do. You have seen all kinds of examples, if you couple ATP hydrolysis
to a reaction you can drive in direction that would normally not go.
You will drive it uphill by splitting ATP. Sometimes you have to do in several
steps, you use more than one ATP if the reaction requires it.
One thing if I didn’t not mention before, biochemist talk about ATP having high
energy bonds. Biochemist do it all the time, it drives organic chemist crazy
because they don’t think of them as high energy bonds. They think of them as
weak bonds.
On way of imagining this, the phosphate has a negative charge, if you have two
negative charges they repel each other.
If you pushing two things together with a negative charge (click them together),
they are going to want to break because they want to relieve the problem of the
negative charges. That can be used to drive the reactions.
There are differences between biochemist and organic chemist do. I won’t go into
it. One of them is that biochemist do not balance their reactions they way organic
chemist do.
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There’s a concept I think is hard to believe for some people- in all these reactions
that we are doing in the body (making different things, and breaking things), these
reactions use up a lot of ATP.
We are constantly making ATP and breaking ATP. People can use radioactive
isotopes, they can determine how much ATP is being made and broken down.
o It turns out that people make a lot.
o One of my professors at UCLA, Boyer got the Nobel Prize for working
out oxidative phosphorylation but he loved to say his lectures how much
ATP the average student would make and that would be about 100kg/day.
That is a big pile of ATP.
o You don’t have that much in you at one time. You are constantly making
it and breaking it..etc.
o You are making it by metabolizing food and other things.
Slide 16- Allosteric Regulation Figure
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And again sometimes, people learn this but they don’t have a feel for this. When I
was a grad student at UCLA, most of my fellow grad students on my floor were
studying enzymes.
The enzymes came from wild cucumbers from the hills of LA, or a electric eel
extracts, bacteria extracts and all kinds of things.
They would find enzyme activity they are they are interested in. They would get
an assay to measure the activity.
Without purifying the enzyme, they would simply do the first experiment. They
would look at the rate of the reaction, depending on how much substrate was
there.
o Almost all the time they would get at hyperbolic curve. You would see it
go up slowly and level off –flat meaning that if you add more substrate
while the enzyme is saturated and it can’t go any faster. This is what they
would see most of the time.
However, 1/10 times they would see the so-called S-shaped curve (Sigmoid) and
go really excited because they can use it for dissertation research.
When this happened, almost certainly it was an allosteric enzyme. That means
that it was regulated by something.
o But, they don’t even know what is regulated by- maybe level of ATP or
other compounds. But, it’s something to study and identify. They don’t
know if it is positively or negatively regulated. This is a characteristic of
allosteric enzyme.
o Allosteric enzymes are almost always the first reactions in a series of
reaction. It’s the reaction of you have to regulate because it’s the first
committed step in a pathway or steps of reactions.
Slide 17- Allosteric Regulation of Enzyme
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Here’s one example of allosteric regulation
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I talked about this when I was discussing glycogen metabolism. First of all,
typical allosteric enzymes they have usually have 2 more subunits, sometimes 4.
You will hardly see one with one subunit.
The idea of allosteric regulation is that the compound that causes the effect binds
at some site other than the active site.
It causes conformation of the protein to change. Remember what happened
phosphorlyase a- it’s phosphorylated and is normally active in the liver. It would
normally break down glycogen to make more glucose.
o However, when glucose levels get high in the blood, what happens is that
glucose binds to this.
o This changes the conformation of the proteins so that it turns from the
relaxed state (Active state) to tense state (inactive state) now it is
inactive.
o The idea is that glucose levels go up, so you don’t want to break down
glycogen to make more. You want to turn off the phosphorlyase a.
o Remember I pointed out this is the molecule that is basically senses the
glucose concentration in blood and plays big role in regulating it.
Slide 18 and 19- Question
 This is to give you the basic idea of regulation. The question is what step in
this pathway is regulated? Please refer to slide to see diagram* I don’t give
you all possible choices possible. If you wanted to regulate one of these steps,
which one would you regulate?
 Answer from student: A> B, no you don’t want to do that because if you
inhibit A, say if you wanted to make more E, but you didn’t need I or H, you
don’t want to regulate this step, because you have shut reaction is down, you
wouldn’t get less of H, E, and I.
 The answer is that step B>C. That is the first committed step to make E. you
wouldn’t want to do this one, because you would shut down H and I. But you
would do this one. It wasn’t a choice.
Slide 20- Covalent Regulation of Enzyme activity
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This is a cascade I should you earlier. One way of regulated things (we talked
about allosteric regulation) is hormonal regulation. Which is often means reverse
phosphorlyation.
I am not going through this pathway again, the idea is that a little bit of hormone
causes a series of effects.
Each step is amplified and then next step you get more, so the last step you get a
1000 fold from a tiny amount of hormone.
And that’s reverse phoshphoslyation, also called hormonal regulation. Hormonal
regulation often occurs on top of allosteric regulation. They both are going on.
Slide 21- Covalent Regulation of Enzyme Activity ctd
 I want to point on little thing here.
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This is protein kinase A is cyclic AMP is dependent. Cyclic AMP activates (he
said deactivate but corrected it) PKA. How does this work?
Slide 22-Modulator Proteins
Turns out this proteins kinase A is tetramer. It has two catalytic and two regulatory
subunits. This is inactive. When cyclic AMP binds to each regulatory subunits, they
dissociated. The catalytic subunits are free and can do their phosphorlyations.
Slide 23- Hormonal Activation of Transcription
 I am going skips this slids because you are going to get a lot more of this when
you get to the nucleic acid lectures. Mumbles…you need to know more about
nucleoic acids regulation.
 Skips slide
Slide 24- Control Sites
 I have listed the major controls sites for the major metabolic pathways. We’ll just
look at these briefly.
Slide 25- Glycolysis
 Lets look at Glycolysis.
 This takes places in the cytosol.
 A typical exam question often will be to ask where these different process
takes place. Some place take place in the mitochondira, and some in the
cytoplasm, and some in the membrane.
 The key enzyme in Glycolysis, or the one that is regulated the most is
phosphofructokinase (PFK).
 PFK, using an extra ATP, adds phosphate to make Fructose-1,6-bisphosphate.
That is inhibited by ATP and citrate.
 Think about this for a moment, these things make sense. What are you doing
Glycolysis for in the first place? You are making more ATP for yourself. If you
have a lot of ATP, you don’t want to do it. So ATP is inhibitor.
 On the other hand, if you have you used up all your ATP, and now you have a lot
of AMP, well the AMP tends to be activate this reaction. You can rationalize
these –how they are regulated.
Slide 26- Gluconegenesis
This is gluconegenesis. We disccused this thoroughly. Remember this regulatory
molecules-Fructose-2,6-bisphosphate. That’s not fructose-1,6-bisphosphate. This is only
small amount and plays a regulatory role. When glucose levels are low, you want to make
more glucose. So you would up regulate gluconegensis.
Also, If they are low you don’t want active Glycolysis- because if you don’t have enough
you don’t want to break it out.
*I would spend few minutes on this later. You can rationalize these effects and they make
sense.
Slide 27- Figure
I will point that ATP is low, so AMP will be high. It will activate Glycolysis. Because if
ATP is low, then you want to make more ATP, so you speed Glycolysis up. To make
more ATP and so on… I won’t read all of these to you.
In every case, you can predict the effect of the molecules like AMP and ATP and citrate
on these pathways.
Slide 28-Citric Acid Cyle or TCA
 The thing to remember is it occurs in the mitochondria.
 Remember, glycolysis in the cytsol.
 There is something called respiratory control. Another name for idea we talked
before.
 The idea the you have to be able to regenerate NAD.
o If you can’t do that, then processes that require NAD will slow rate down
to a stop.
 In the citric cycle, you are making a lot of NADH.
 That NADH and the FADH2 are re-oxidized in the oxidative phosphorlyation in
the mitochondria and produce ATP.
o If you have enough ATP, that doesn’t happen. What then happens is, this
NADH is not oxidized, and you don’t regenerate NAD. So things slow
down. That’s called respiratory control.
 Called respiratory because of the oxidations that occur in the
mitochondria and if you don’t need to do it, you don’t regenerate
your NADH (that’s word for word what he said). ***Earlier he
said you don’t regenerate NAD***
Slide 29 Pentose Phosphate Pathway PPP
 The first committed step is the glucose-6-phopshate dehydrogenase. Remember
this is enzyme that if you have happened to have the defective form of the
enzyme, you will be one of 400 million people that have this deficiency.
 Under certain circumstances, you could get acute hemolytic anemia episodes.
 The point is that if you got have a lot of NAD+, then that speeds up the reaction.
 **He started to make no sense..so I transcribed what he said**
 That would make sense because that means you don’t have enough NADPH. You
need the NADPH for reductions.
o So, basically if you don’t have enough NADPH, and you have a lot of this,
the reaction speeds up so you can more NADPH. That is also logical.
Slide 30- Glycogen Synthesis and Degradation
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Glycogen metabolism, is what we were talking about.
The idea is there are two types of regulations and both are going on at the same
time. There is the hormonal regulation by phosphorlyation.
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Phosphorolyation activates the enzyme that breaks down glycogen and inactivates
the enzyme that makes glycogen.
The opposite dephosphorlyation has the opposite effects. I told you earlier about
alleostric effects of glucose in the liver on phosphorlyase a.
In the muscle, not the liver, when you start using up all your ATP, you got a lot of
AMP.
o AMP activates phosphorlyase to break down more glycogen so that you
now have glucse to run through Glycolysis to get more ATP.
Slide 31- Fatty Acid Synthesis
I am skim over this since I did not teach this.
 The whole idea is the first committed step is this acetyl CoA carboxylase step. It’s
stimulated by citrate.
 Remember, citrate builds up when you are not running through the citric acid
cycle to make more ATP.
o When you have a lot of ATP and acetyl CoA, you are not going to be
running the TCA to make more.
 The citrate builds up activates this reaction so basically you have an acetyl
CoA that you don’t need to burn in TCA, so you turn into FAT! That’s
what’s happening here.
Slide 32- Fatty Acid Degradation
 Fatty acid degradation is called Beta oxidation.
 It occurs in the mitochondria.
 You have learned this from Dr. Baggot that carnitine is sponsor for
transporting fatty acids in the mitochondria. That’s regulated then.
 If you build up a lot of this intermediate in making fatty acids, it will then
inhibit this reaction- bringing the fatty acids into the mitochondria.
Slide 33- Camel
(Side Story) When I was a little kid, it was common to for people to say that camel
carries water in the humps and that’s why it can go for days and days without water in the
desert. Well it turns out, camels don’t carry water in the hump. They carry fat, and that
turns out it’s better to carry fat than water. People who have studied this, 4 gallons of fat
can be turned into 26 gallons of water. You think this wouldn’t make sense. The mass of
water is quite large – gallon weighs 8 lbs. Four gallons of fat- it’s not going to be that
much. How is possible?
How can you get more mass out of fat? Think about this. Where does most of the mass
come from? It comes from the AIR! The camel oxidizes the fat, the fat is the source of
the hydrogens. The oxygen comes from the air. If you are being smart about it like a
camel, it’s easier for your to carry around fat, instead of water. You can get oxygen from
air and turn into water.
Slide 34-Table
 If you care, these are the reactions that are involved in the breakdown of fatty
acids. You can look at the sum of the reactions.
 The net effect is that you have a lot of water from breaking down fat.
Slide 35- Whale
 This killer whale, apparently they don’t drink sea water. They eat seals, fish, sea
otters and other things and they make their water by breaking down their fat.
Slide 36- Key Junctions
 Here’s this metabolic pathway. Here are these key junctions that I talked about.
There’s glucose-6-phosphate, pyruvate, acetyl CoA.
Slide 37- Glucose Regulation
 Remember, I told you that glucose enters the cells, it is immediately
phosphorylated by hexokinase.
 Now, this glucose-6-phosphate can go a bunch different ways.
 The way it goes depends on what the cell needs.
 Now, if the cells needs ATP (energy), it funnel glucose-6-phosphate through
Glycolysis. Then you end up with pyruvate, which can be converted to acetyl coA
which goes through TCA and make more ATP.
 If the cell needs to make fat or something else, it might need more NADPH. It can
go through the PPP or if it needs to make DNA/RNA, this is a way to make more
ribose-5-phosphate.
 On the other hand, if you don’t do need to either of these things, then the cell
(muscle and liver cells ) will decided to store the extra glucose as glycogen.
 The glucose 6-phosphate is readily converted to glucose-1-phosphate by
glucomutase. Then that’s the converted to glycogen. The route the glucose 6phosophate takes depends on what the cell needs.
Slide 38- Pyruvate/Acetyl CoA
 Remember if you are vigorously exercising and you need to regenerate this NAD
that you made, what happens is that the NADH is then used to reduce pyruvate to
lactate to regenerate the NAD.
 The pyruvate can be also converted to alanine by using a transaminase.
 Or this pyruvate can be used as a starting material to make glucose.
o It will be convert to oxaloacetate then to make glucose in gluconeogensis.
 Acetyl CoA can be used to make fatty acids go through TCA and make CO2. It
can be used to make steroids like cholesterol or ketone bodies.
Slide 39- Fuel Storage
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I have talked about this before and Dr. Miller has too. The major fuel depots are
fat. Fat is the major one.
Then glycogen in muscle and liver. Nowhere near as much energy as fat. Finally
proteins from skeletal muscle.
Normally, almost never use proteins from skeletal muscle, you would have to be
starving to this.
This is the order of use, protein is the last resort.
Slide 40-Table
 Again, I have shown this slide before, I can’t remember.
 There’s far more ATP from breakdown of fat than there is free ATP in the
muscle.
 You can get a fair amount of ATP generated by glycogen anerobically.
 But, if you do it aerobically instead of making lactate at the end, you have
pyruvate that can put in the TCA cycle, you get a lot more energy.
Slide 41- Fuel Use During Exercise
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How fast you can run or exercise or do anything depends on how fast you can
make energy to do it. You can’t run faster than the amount of ATP you have or
can make.
If you have short spurt like 100m sprint (it might take 10 seconds for some
people), what happens is the body uses the stored ATP, and creatine phosphate
and starts breaking down glycogen and doing anerobic Glycolysis. It can do that
very fast.
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It turns your run fast if you’re only running 10 seconds.
If you are only running 1 kM, then you rapidly you will use up the creatine
phosphate and much stored ATP and anerobically Glycolysis starts producing a
lactic acid.
o You can’t run as fast.
o Some of the ATP that is made for the 1Km ends up coming from oxidative
phosphorlyation, but it’s much slower.
Slide 42- Fuel Use Ctd
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If you were running a marathon which takes a long time, you completely deplete
creatine phosphate and glycogen supply (told you about this when we studied
glycogen metabolism).
A lot of the ATP for a marathon comes from fatty acid breakdown.
Exercise physiologist that study this found that good marathon runners get half of
their energy from fatty acids and the other half from glycogen breakdown.
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It turns, even though you are running, the body is doing gluconeogensis to
regenerate glycogen supplies.
Slide 43- Figure
 This shows you how fast you deplete your ATP and your phosphocreatine. And
how anaerobic metabolism works for a while, but as lactic acid levels build up it
goes going down.
 This is showing how aerobic metabolism including aerobic Glycolysis and beta
oxidation goes up only to a certain point. We’re only talking two minutes.
Slide 44-Brain
 Brain uses a lot of glucose. To burn up the glucose, it needs a lot of oxygen. Brain
uses 20% of the oxygen but only 2% of the body mass.
 Whenever you see things like this (referring to slide), this means that it’s for
someone sitting around.
 If you’re vigorously exercising, you’re going to be using a lot more oxygen for
your muscles.
 Brain has no fuel reserves. No glycogen or fat. Expressions like fat head don’t
exist because you don’t store fat in your brain.
 I pointed out why the brain uses so much ATP is because it maintains the
membrane potential of billions of neurons.
 The normal fuel is glucose for the brain but the ketone bodies will work.
 Fatty acids are major source for muscles, but they are not used in the brain.
 The reason is because fatty acids are carried on albumin (from Dr. Baggots
lecture).
o Those big molecules can’t get across the blood brain barrier.
o Only small molecules like glucose and ketone bodies can get to the brain.
We can use some ketone bodies, but the brain absolutely requires
glucose.
o You can uses about 1/3 ketone bodies, the rest has to be glucose. The
ketone body- term bugs me, because it’s not a body.
o They are little molecules of acetone, acetoacetate and betahydroxybuterate. The ketone bodies are being used all the time whether
not you are starving.
o A question is asked that is inaudible. His response: no, they are being
made and used all of the time (I think he was referring to ketone bodies).
 If you people go on severe low carb diets, they measure ketone bodies in their
urine.
o They feel if they get lots of ketone bodies, and if they get a lot in urine,
they think they are succeeded. Other people think that is not good to have
that many ketone bodies.
Slide 45- Muscle

Depends if you exercising vigorously, the muscles can end up using a lot of
oxygen and fuel.
 Resting muscles tends use fatty acids- favorite fuel of muscles, also use glucose
and ketone bodies.
 Resting muscle you get aerobic Glycolysis with oxygen phosphoplyation.
 Vigorously exercising, you can’t get oxygen to the muscles fast enough, so
pryuvate is produced which is converted to lactate.
 Point out that resting muscles contains glycogen and small molecule
phosphocreatine.
o The phosphocreatine will rapidly reconvert ADP and AMP to ATP. It
recharges the ATP levels. It does it fast.
Slide 46- Figure



I talked about the Cori cycle.
The exercising muscle produces lactate, and that goes to the blood stream and
converted to the glucose and goes back to the muscles.
It turns out the pyruvate can be converted to alanine and can be go through the
blood stream and be transaminated to pryuvate which will go through
gluconeogenesis to make more glucose.
Slide 47- Phosphocreatine
 Told you it’s purpose to regenerate the ATP. Stores like walmart, they sell
creatine in big containers, and people take these.
 The interesting thing is that it does increase the levels of phosphocreatine in
muscles. The level of most molecules is highly regulated.
 Unless you are a diabetic, you can eat a lot of glucose and that doesn’t push your
glucose level up too much. Most substance are highly regulate.
 However, you can get almost double creatine levels by taking the supplements of
createine.
o Some people say it’s hard on your kidneys.
o I told you it only lasts for a few seconds. So, if you are long distance
runner or swimmer, that extra phosphocreatine will not do you any good.
o If you’re a weigh lifter where you need few seconds of extreme output,
then apparently it does work. It does help.
o Endurance athletes don’t get benefit out of it.
Slide 48- Heart
 Heart is completely aerobically.
 There is no anaerobic Glycolysis or lactic acid unless one something is seriously
wrong.
Slide 49- Adipose Tissure
 People can store lots of energy as fat- this slide says 3 months but depends on
how much fat you have.
 When fat is broken down in fat cells, it’s broken down to fatty acids and glycerol.
 Unfortunately, the fat cells lack enzyme to add phosphate to the glycerol, so the
fat cells can’t use the glycerol to make new fat when it does the other direction.
o So the fat cells have to phopshoglycerol from the liver.
 The way it happens is that the liver cells need glucose, and the
glucose gives the dihydroxacetate (I believe he meant DHAP) that
can be reduced to glycerol phosphate.
 It can be used to make new fat.
 The liver cells also need glucose so they can breakdown it down by the PPP to
make NADH to be used in fatty acid synthesis.
Slide 50- Adipose Cell
 You can study this. Take home is that fatty acids are traveled on albumin and
glycerol goes to the liver..he mumubled this.
Slide 51- Kidneys
 Kidneys are big users of oxygen.
 Blood is filtered out in the kidney, and stuff is taken up again.
 That reabsorption takes a lot of energy.
 So the kidneys require a lot energy even if they don’t weigh a lot.
Slide 52- Liver
 The liver does all kinds of things. Remember it makes food for everyone else.
 Most of the glucose that is absorbed in intestine is taken up by the liver.
 The glucose can be broken down in Glycolysis, converted to glycogen, or
converted to ribose-5-phosphate in the PPP.
Slide 53- Liver Continued
You can read this over. Falling behind.
Slide 54- Liver Ctd
 The liver is important for amino acid metabolism.
 When you break down Amino Acid, you tear off the nitrogen, then use the keto
acids that are left behind that are converted or used for energy.
 The nitrogen that is torn off is converted to urea. We secrete urea every day
especially if you have high protein diets.
o The reason is its urea is because it is a non-poisonous compounds.
 If we secreted ammonia (highly alkaline) it would be toxic.
Slide 55- Table
 This summarizes some of the stuff I have been pointing out to you.
 Notice that they are talking about preferred fuel for the organs. Preferred food:
Brain is glucose, muscle is fatty acids also use glucose, heart is fatty acids.
 The liver is different.
o The liver makes food for everyone else; it breaks down amino acids to
keto acid.
o The liver is preferred food is the keto acid produced by the break down of
amino acids.
Slide 56
Energy charge is defined by this (pointing on slide). This is sum total of all the
adenosyl phosphates the ATP and AMP and ADP. You count two ATPs because
you have two hydrogen phosphates.
Slide 57- Figure
 The effect energy charge is measure of the proportion of ATP in a cell. If you
have 100% ATP, then you have 1 for electric charge.
 If you have 0% then you have would have 0 for the electric charge.
 It would never be like this.
Slide 58-Figure

Then it turns out all these reactions that generate ATP, work fastest when there is
low ATP. If ATP levels go up, then they are all turned off. Similarly for the
reactions that use ATP.
Slide 59 – Figure
 What happens is there is steady state point where theses reactions are… you can
see what happens here (doesn’t complete thought).
 You can see an oscillations as these reactions are generating ATP are working on
opposite in the reactions that are using ATP.
 People can look at it electronically. There are enormously sensitive devices.
 You can see the electric charge in the cell is going up and down and up and down
and oscillates continually.
 Most cells at steady state is about .8.
FROM SLIDES 50-59 he flew past them to squeeze all of the information in
before the break—please refer to your slides to further clarify anything.
--Break--