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L10v01a_intro_to_metabolism
[00:00:01.06] SPEAKER 1: Hi. With this video we begin the second portion of the course, where we'll look at
things at a more integrated systems level, rather than the molecular level which we concentrated on in the
first portion. In this lecture, specifically, we'll speak about metabolism and how the food we eat performs two
main functions. It provides the energy we need for cellular processes, and it provides molecular building
blocks for the compounds cells need to synthesize.
[00:00:30.41] We'll discuss how we capture energy from energy rich compounds like carbohydrates, glucose,
how we oxidize them, which is basically burning them, capturing some of the energy released, and converting
the carbon atoms to carbon dioxide. We'll talk about how surplus food is stored as fat or glycogen, and we'll
talk a little bit about some of the dietary trends that have been rampant in Western civilizations for the last 30
or 40 years.
[00:01:04.87] Which will come as no surprise to you, we eat too much processed food with too much sugar. To
drive this point home, I've assigned a YouTube video from another university that's by Doctor Lustig at
University of California, San Francisco. It's called Sugar: The Bitter Truth, and it has over four million views on
YouTube. It's 90 minutes long, and it's worth watching the entire thing. We'll be responsible, we will actually
test on some of the major points, but I think you'll find the story very interesting otherwise.
[00:01:42.28] This is a metabolic network of some of the known reactions that occur inside cells. It comprises
over 7,000 reactions and 5,000 different molecules. It's tremendously complicated, but recently scientists
have been able to start analyzing this network in manners somewhat analogous to the way electronic circuits
are analyzed, which is powerful computationally. And this is a vastly simplified view of metabolism.
[00:02:12.69] What it depicts is the fact that the input molecules are energy rich carbohydrates which are
oxidized in a process down to removing the energy content down to inorganic carbon dioxide. Various
metabolic intermediates, before it gets to carbon, can be siphoned off and used to synthesize molecules that
we need, amino acids, nucleic acids, and lipids. And also it highlights that while we are oxidizing the
carbohydrates, we're capturing energy in the form of ATP, which is synthesized from ADP, and this provides
the energy for many of the uphill energetic reactions that are needed to synthesize these larger molecules.
[00:02:59.31] This process of oxidizing sugars down to carbon dioxide is so central to life it's known as central
metabolism, and there are two main parts, glycolysis and the citric acid cycle. The glycolysis happens in the
cytosol. It's where glucose will get converted down. A six carbon sugar, as you know, will get converted down
to pyruvate, a three carbon sugar. The pyruvate will get converted into acetyl-CoA, which it will enter into the
citric acid cycle in the mitochondria, and there you will be producing carbon dioxide.
[00:03:37.46] As we go through this oxidation process from glucose down to pyruvate, we can siphon off
intermediates for the synthesis of various molecules like amino acids, fatty acids, and sugars. And in the
meantime we'll capture energy in the form of ATP. The details of this process will be explained in this set of
lectures and the next set of lectures.
[00:04:04.02] So that was the breaking down part of the metabolism, and here's what we know about the
building up part of the metabolism. In many bacteria, many organisms, we know the exact proportion of the
amino acids, phospholipids, nucleotides, other cofactors that we need to synthesize in order to support cell
division, new cells. And this lays the foundation for the calculations that people are able to do.
[00:04:33.87] As you can see, we know what the input is, and we know the connectivity of that metabolic
network. Think back to that very complicated slide. So how does the biomass percolate through the network
in order to produce these molecules in these relative amounts for cell growth. That it works as well as it does
this rather amazing, and it really heralds the future in terms of how computational approaches can really be
predictive in biological experiments.
[00:05:10.09] As we mentioned, as we're oxidizing glucose some of these intermediates can be siphoned off to
make amino acids, here, here, and here. And I just want to keep that in mind as we look at the next slide,
which is to emphasize that humans can only make 10 of the amino acids from sugars. That is, even if our diet
contained none of these 10 amino acids, we would have no problems producing them.
[00:05:42.80] However, we do have 10 amino acids which are called essential, and the only way that we get
these is by direct ingestion. It's interesting to speculate about it evolutionarily. The lowly bacteria, and even
chicken, can make all 20 of the amino acids. But somehow, humans have lost that ability to make 10 of them.
[00:06:05.69] In the next lecture, we'll talk a little bit about photosynthesis. And here I just want to take the
big picture view of its relationship to respiration. They're in many ways the inverse processes. Again, to recap
what we do, we eat sugars, we breathe oxygen, we oxidize the sugars down to carbon dioxide, and we extract
that energy to create useful chemical bonds.
[00:06:34.02] All the sugars are made for us by photosynthetic organisms. Those photosynthetic organisms
produce oxygen when splitting water. They take carbon dioxide out of the environment, and in a process
called carbon fixation will take in organic carbon dioxide and create organic sugars. And all of this is powered
by the energy of sunlight.
[00:07:00.08] Since global warming is a topic of interest to many, I'll just point out that if we were able to
increase the amount of photosynthesis that occurs on the planet, we can take carbon dioxide, a greenhouse
gas, out of the environment and trap it essentially into sugars. So when we speak of oxidation of sugar
molecules, it's exactly what happens in a fire. There is a large amount of energy from the fire that will cross at
large activation energy for fragmenting sugar [INAUDIBLE]. All the energy is released as heat, and carbon
dioxide and water is produced.
[00:07:40.25] But inside cells we burn-- quote unquote, burn-- sugar molecules in small steps in a controlled
manner which allows us to capture a lot of the energy present in the molecule. Overall, I believe we capture
about 37% of sugar energy. So still a lot will get lost, but nevertheless that's quite an impressive engineering
feat. This is an overview of digestion.
[00:08:12.31] Stage one, where we are eating molecules, proteins, polysaccharides, and fats, and they begin to
get digested right away in our mouths due to salivary enzyme. They get further digested in our stomachs and
intestines with gastric and pancreatic enzymes. They will eventually enter into the bloodstream. They'll get
taken up by cells, and out here in the cytosol we'll see glycolysis, which is the breaking down of glucose to
three carbon pyruvate. It'll get transferred into the mitochondria, where it will enter into the citric acid cycle,
which will produce a high energy intermediate molecule NADH.
[00:08:59.88] We will study stages one and two today. In the next class session, we'll look at how NADH gets
converted into ATP in the process known as oxidative phosphorylation.
[00:09:16.33] When food is digested and broken down into small molecules, it enters from the small intestine
into the bloodstream, which goes directly to the liver, which is the main processing plant of nutrients, and
several things can happen to the food. It can get stored as glycogen, or fatty acids, as fat tissue. It can transfer
via the bloodstream to organs and tissues like muscle, or the glucose can be either converted into glycogen at
the muscle, or used directly for energy production.
[00:09:58.41] Or in periods of high demand when we don't have sufficient oxygen, it can be digested
anaerobically into lactate. This is what causes muscle cramps, but nevertheless provides a little bit of energy
for your muscles to use. One thing specifically that cannot happen when we're talking specifically about
carbohydrates, is that it cannot, in humans, be turned into amino acids for protein production.
[00:10:26.41] The fat in adipose tissue is stored as triglycerides. Again, we have the glycerol backbone with
three fatty acids attached to it. This is the densest form of storing energy in the cell, more compact than
glycogen, and it is stored in vesicles as fat droplets inside fat tissue. Glycogen can accumulate in livers or
muscle cells, as we've shown, and these are branched glucose molecules, which can rapidly be cleaved
producing glucose molecules that are available for immediate metabolic needs. When you consume food,
there is a rich supply in the bloodstream, and it can transfer to all the cells of your body which can use them
for their metabolic needs.
[00:11:16.24] In between meals when we get hypoglycemic, or we don't have a huge influx of nutrients, we
can get energy from stored fat which is hydrolyzed into fatty acids from a fat cell. These will enter the
bloodstream, and then these fatty acids can supply muscles and other tissues as an energy source for the
production of ATP.
[00:11:41.09] OK. Thank you for listening.