Making Squalene

 
Squalene is the essential precursor for making cholesterol [How to Make Cholesterol]. The pathway for synthesis of squalene is complicated and it was only worked out in second half of the last century.

The initial substrate is a compound called mevalonate. It's a six carbon branched organic acid. In a later posting we'll wee how cells make mevalonate and learn how that pathway can be controlled by Lipitor® and other drugs that regulate cholesterol levels.

Mevalonate is first phosphorylated by mevalonate kinase in a reaction that requires ATP.


The product of this reaction is mevalonate-5-phosphate and it is immediately phosphorylated again to produce the disphospate derivative. The next step removes the carboxylate group, which is released as a bicarbonate ion (CO₂ dissolved in water produces bicarbonate). This decarboxylation reaction is associated with the formation of a double bond at the end of the product molecule, isopentenyyl diphosphate. This is an important step in the pathway to squalene since squalene has a lot of carbon-carbon double bonds.

The five-carbon isopentenyl group of isopentenyl diphosphate is known as an isoprenyl unit. This molecule (isopentenyl diphosphate) is the source of isoprenyl units for many other biosynthesis reactions in addition to squalene synthesis. &Beta:-carotene and the lipid vitamin A (retinol) are good example of compounds with these isoprene units [Vitamin A (retinol)]. Ubiquinone is an absolutely essential cofactor in many important biochemical reactions an it has an isoprenoid tail [Ubiquinone and the Proton Pump]. Vitamin K, which is required for blood clotting, has a derived isoprenoid tail [THEME: Blood Clotting].

The pathway from isopentenyl diphosphate to squalene is complicated but the basic strategy is quite simple. The idea is to join two five carbon (C₅) isoprene units to make the C₁₀ molecule geranyl diphosphate. Then another C₅ isoprenyl unit is added to make C₁₅ farnesyl diphosphate. Finally, two molecule of farnesyl diphosphate are joined head-to-head to make C₃₀ squalene.


The difficult part of this reaction was figuring out the mechanism so that all of the double bonds would be in the trans conformation. Most of the work was done by John Cornforth who received the Nobel Prize in 1975 [Nobel Laureate: John Cornforth].

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Praying for Rain

 
Here's a video from CNN of Georgia Governor Sonny Perdue praying for rain [Georgia's governor prays for rain on Capitol steps]. It's the sort of thing you might expect from a tribe of hunter-gathers about 50,000 years ago. It didn't work very well back then. I wonder if it will work today?

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Free Your Mind

 

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[Hat Tip: PZ Myers]

DNA Is Life T-Shirt

 

Edmund Scientific is selling a T-shirt with a picture of a replicating DNA molecule [DNA is Life T-Shirt].

The caption reads "DNA Is Life. THE REST IS JUST DETAILS." Clever, but sometimes those details are important.

Look closely at the T-shirt. How many of you recognize what's wrong with the molecule on the T-shirt? It may be "just a detail" but I wonder why they couldn't have designed a logo that was scientifically accurate?

How difficult can it be? Would they sell fewer T-shirts if the molecule was accurately depicted?

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[Hat Tip: Hsien-Hsien Lei]

How to Make Cholesterol

 
Monday's Molecule was squalene, a thirty carbon lipid with a characteristic set of double bonds [Monday's Molecule #51]. Most species can synthesize squalene. In some, it serves as the precursor for biosynthesis of cholesterol and other complex steroids.

Cholesterol is an essential component of cell membranes and the initial substrate in pathways leading to hormones such as testosterone and β-estradiol.

A brief outline of the pathway from squalene to cholesterol is shown on the right. The first thing to note is that squalene can fold into a form that already resembles cholesterol. The reactions in the pathway result in closing the rings to make the four ring structure that's characteristic of steroids.

Lanosterol is a key intermediate in this pathway. Note that in addition to the ring closing reactions, an oxygen—in the form of a hydroxyl group—has been added to the ring.

The conversion of lanosterol to cholesterol requires up to 20 enzyme-catalyzed steps. There's more than one way to make cholesterol from lanosterol but in the end all molecules of cholesterol are identical.

Most species, including humans, are capable of synthesizing all the cholesterol they will ever need. In animals, the biosynthesis pathway is regulated by the amount of cholesterol in the blood plasma. If a large amount of cholesterol is derived from food then the biosynthesis pathway is down-regulated to compensate.

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National Center for Science Education

 
The National Center for Science Education (NCSE) has a new log by graphic artist Andrew Conti. Do you know what it depicts? [NCSE Logo Contest Winner].

Check out the NCSE homepage for a ton of useful information about the evolution/creationism debate [NCSE]. You can even sign up for a Grand Canyon River Raft Expedition with NCSE geologist Alan Gishlick to explain the real scientific history and "creationist" Eugenie Scott to explain the other kind of history.

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[Hat Tip: John Pieret]

Monday's Molecule Copycat

 
One of my offspring—who shall remain nameless—has decided to make fun of my Monday's Molecule feature. Go to her blog and tell her to behave herself [The Monday Molecule - Belgium Version].

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Monday's Molecule #51

 
Today's molecule may seem very simple but your task is to give it a complete IUPAC name as well as the common name. You also have to identify the origin of the common name. Pay close attention to the structure before you venture a guess.

There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this week's reward. The prize is a free lunch at the Faculty Club.

Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule, the origin of the common name, and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: We have a winner! Satoris guessed that the molecule was squalene [2,6,10,15,19,23-Hexamethyl-2,6,10,14,18,22-tetracosahexaene] and the name squalene is derived from squalus meaning "shark." Squalene was first isolated from shark liver. The word squalus comes from the Latin word squalus. It originally meant any marine fish.

Several people got this part right but Sartoris was the only person to guess the correct Nobel Laureate. I was thinking of the person who worked out the detailed pathway for biosynthesis of squalene. You will find out tomorrow.

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Reading Level Comparison

 
BarryA has posted the following comment on Uncommon Descent [Reading Level Comparison].

Thanks to one of our commenters for pointing out this website that calculates the reading level of blogs. Just for fun I inserted UD and it came back “High School,” which means that the general discussion at this blog is at a high school level. I then inserted Pandas Thumb and it came back “Elementary School.”

Make of this what you will.

This seems curious so I tried it myself. Here's the result for "www.uncommondescent.com."

Uncommon Descent

and here's the result for "pandasthumb.org"

The Panda's Thumb

Make of this what you will. For me, it brings to mind the word "IDiot."

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The Salem Conjecture

The Salem Conjecture was proposed by Bruce Salem on the newsgroup talk.origins [The Salem Conjecture]. Here's how he described it on Sept. 5, 1996.

My position is not that most creationists are engineers or even that engineering predisposes one to Creationism. In fact, most engineers are not Creationists and more well-educated people are less predisposed to Creationism, the points the statistics in the study bear out. My position was that of those Creationists who presented themselves with professional credentials, or with training that they wished to represent as giving them competence to be critics of Evolution while offering Creationism as the alternative, a significant number turned out to be engineers.

This should not be confused with the "hard" version of the Salem Conjecture (Hypothesis), which says that engineers are more likely to be creationists. Both versions are described in the Wikipedia entry [Salem Hypothesis].

Joshua Rosenau discusses the possibility that the hard version of the Salem Conjecture might be correct and this explains the soft version [The Salem Hypothesis explained!]. Read the comments.

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[Photo Credit: I pretty sure this is a photograph of Bruce Salem.]

Beyond Belief II: Enlightenment 2.0

 
By all accounts this year's Beyond Belief symposium in San Diego was a lot less exciting than last year's [Beyond Belief II: Enlightenment 2.0]. Perhaps it's because Richard Dawkins wasn't there. On the other hand, PZ Myers was there [Speakers].

There's a short review of the highlights in this week's issue of New Scientist [Does God have a place in a rational world?]. From the sounds of it, the lack of clear-headed atheists led to some very sloppy thinking.

The first firebrand is lobbed into the audience by Edward Slingerland, an expert on ancient Chinese thought and human cognition at the University of British Columbia in Vancouver, Canada. "Religion is not going away," he announced. Even those of us who fancy ourselves rationalists and scientists, he said, rely on moral values - a set of distinctly unscientific beliefs.

Oops. I've got news for you, Prof. Slingerland, you can't count yourself as a rationalist if you think that morality requires religion. And you can't lay claim to being a scientist if you think that moral values are unscientific. That's two strikes.

Where, for instance, does our conviction that human rights are universal come from? "Humans' rights to me are as mysterious as the holy trinity," he told the audience at the Salk Institute for Biological Studies. "You can't do a CT scan to show where humans' rights are, you can't cut someone open and show us their human rights," he pointed out. "It's not an empirical thing, it's just something we strongly believe. It's a purely metaphysical entity."

Strike three. It's a good thing Dawkins wasn't there or this kind of sloppy thinking would have been exposed.

Who said we all have a conviction that human rights are universal? Not me, that's for sure. I can't think of a single "human right" that qualifies. Furthermore, those human rights that we generally agree upon in the 21st century are not mysterious to me. They're mostly common sense designed to maximize our ability to live in groups. It's an empirical thing—and we're still working on the best compromises between absolute rights and qualified ones.

The mood at this follow-up conference was different. Last year's event was something of an "atheist love fest" said some, who urged a more wide-ranging discourse this time round. While all present agreed that rational, evidence-based thinking should always be the basis of how we live our lives, it was also conceded that people are irrational by nature, and that faith, religion, culture and emotion must also be recognised as part of the human condition. Even the title of this year's meeting, "Beyond Belief II: Enlightenment 2.0", suggested the need for revision, reform and a little more tolerance.

Hmmm ... I guess I can go along with that. I've known for some years that people are attracted to irrationality and superstition—we call it religion. We tolerate those who ignore rationality and evidence-based thinking but that doesn't mean we shouldn't criticize those who think that way, right? Tolerance doesn't mean the same as acceptance, does it?

There's one comment in that paragraph that puzzles me. Is it true that people are irrational by nature and it's part of human nature? My observations suggest the opposite. It seems to me that most humans strive to be rational as opposed to irrational. They may get confused from time to time about what is rational and what isn't but over the centuries rationalism tends to win out over superstition. Why do we have to concede that superstition is here to stay because it's pat of the human condition. That doesn't make sense.

Such was the message from evolutionary biologist David Sloan Wilson of Binghamton University, New York. He suggested that humans' religious beliefs may have evolved over time, thanks to the advantages they conferred as a sort of social glue holding together groups that developed them.

Wilson was not saying religion is good or bad, simply that it has evolved to be hard-wired into our brains, and therefore cannot be ignored. "Adaptation is the gold standard against which reality must be judged," he said. "The unpredictability and unknown nature of our environment may mean that factual knowledge isn't as useful as the behaviours we have evolved to deal with this world."

Hmmm ... if irrationality and superstition are hard-wired into our brains then how come it's so easy for many of us to escape from this sort of thinking?

I often wonder whether people like Wilson have thought seriously about what they're saying. Does he imagine a time when primitive humans didn't have religion because it hadn't yet evolved? How did those groups manage to survive? I wonder what went on in their brains when they couldn't think about supernatural explanations?

Or did the religion allele(s) arise before the hominid lineage? Have chimps got religion and that's what what makes them stick together? (Instead of sex.) What about gorillas? Who do they worship? Howler monkeys? Meerkats?

Chemist Peter Atkins of the University of Oxford, one of the more hard-line atheists in the room, did not let this go unchallenged. He chided fellow participants for not being sufficiently proud about what science can accomplish. Given time and persistence, science will conquer all of nature's mysteries, he said.

I'm glad to see there was at least one rationalist present.

So can scientific and religious world views ever be reconciled? Harris, author of The End of Faith, declared that they could not, and provided an uncompromising exposition on the evils of religion.

Away from the meeting, philosopher Daniel Dennett of Tufts University in Medford, Massachusetts, told New Scientist that as irrational as human minds may be, calm, firm introduction of reason into the world's classrooms could over time purge them of religion.

Maybe there were more rationalists present than the author of the piece is willing to admit?

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[PhotoCredits: Beyond Belief II: Enlightenment 2.0, Meerkats]

With Friends Like This ....

 
Greta Christina has a blog called Greta Christina's Blog (naturally). She posts lots of interesting stuff about atheism and other things. Today she strayed into science and posted a video about macroevolution (see below) [Macro-evolution" Vs. "Micro-evolution": More Video Fun]. Greta introduced it with ...

First, just so everyone's clear: "Macro-evolution" and "micro-evolution" are made-up words concocted by creationists to make themselves sound scientific. Biologists don't use them. They're scientifically meaningless. They're just different stages in the evolutionary process; "macro" is just "micro" over a longer period of time.

I posted this comment on her blog.

I'm afraid you have been mislead. Microevolution and macroevolution are perfectly good scientific terms and they are used by evolutionary biologists all the time.

There is legitimate scientific debate about whether macroevolution is more than just lots of microevolution or whether macroevolution encompasses mechanisms not seen in microevolution. It's the sufficiency of microevolution argument.

I happen to be one of those scientists who agree with Stephen Jay Gould that there are many levels of evolution (hierarchical theory). Thus, macroevolution cannot be sufficiently explained by lots of microevolution. There are other things going on at the higher levels [Macroevolution].

The video is very misleading because it assumes a simplistic version of macroevolution. There aren't any evolutionary biologists who believe in that kind of macroevolution. Thus, I have to conclude that the makers of the video are as ignorant of evolution as the creationists they mock.¹

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¹The video was made by cdk007 who claims to have a Masters degree in Biology and a Ph.D. in Molecular Neuroscience.

[The science book covers pictured are:

Macroevolution: Diversity, Disparity, Contingency: Essays in Honor of Stephen Jay Gould

At the Water's Edge: Macroevolution and the Transformation of Life

Genetics, Paleontology, and Macroevolution]

The Photosynthesis Song and a Pet Peeve

Photosynthesis is a process where light energy is captured and converted to chemical energy in the form of ATP. The basic process is similar to that in membrane-associated electron transport. In both cases an energy source (light or reducing equivalents respectively) is used to create a proton gradient across a membrane. The dissipation of this gradient as protons move back into the cell drives the synthesis of ATP.

In addition to ATP, most types of photosynthesis can also be coupled to synthesis of NADPH. The chemical energy molecules derived from photosynthesis (ATP and NADPH) are used in many different biochemical pathways such as DNA synthesis, protein synthesis, fatty acid synthesis and carbohydrate synthesis.

Most photosynthetic organisms can fix carbon dioxide and make carbohydrates using ATP and NADPH [The Calvin Cycle] [Fixing Carbon: the Rubisco Reaction]. Many nonphotosynthetic organisms can do this too. In photosynthetic bacteria and photosynthetic protists this pathway uses only a small part of the chemical energy created by photosynthesis. In large plants the synthesis of carbohydrates can use up a significant portion of the ATP and NADPH generated by photosynthesis.

The fixation of CO₂ and the synthesis of carbohydrates used to be called the "dark reactions" of photosynthesis back in the days when all we knew about were big plants. We didn't know anything about the biochemistry of photosynthetic bacteria or other species. Because our attention was focused on big plants, it was thought that photosynthesis was always coupled to the carbohydrate synthesis pathways. Now we know that this isn't true, so the old-fashioned equation,


is just not a valid representation of photosynthesis. The real products of photosynthesis don't even appear in the equation and, furthermore, those products are used for many different purposes inside the cell (especially in bacteria). Not only that, in some photosynthetic bacteria the electron donor isn't water but some other inorganic molecule like H₂S and S₂ is produced instead of oxygen. The equation is very misleading on many levels and should be abandoned.

Greg Laden has posted the video shown below and commented on the fact that the word "miracle" is used [The Photosynthesis Song ... Bad Word Choice?]. I'm much more worried about the misleading science in the video than I am about one instance of the word "miracle."

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FOX News Anchor Want USA to Support Terrorism

 
This is really quite incredible. Brain Kilmeade is the co-host of of the Fox and Friends morning news program. He thinks the USA should support terrorists inside Iran who will set off car bombs in Tehran. The conservative right really doesn't get it, do they?

The war against Iran is coming soon to a theater near you.

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[Hat Tip: Jim Lippard]

Cafe Inquiry

 

The Centre for Inquiry (Toronto) and the University of Toronto Secular Alliance are pleased to announce the first Cafe Inquiry. These monthly meetings will focus on topics of interested to the secular community.

The first meeting is going to be held in conjunction with a series of lectures sponsored by CFI. The speaker happens to be me, talking about Evolution as a Theory and a Fact. If you haven't had enough of me on this blog, then come out to the Centre for Inquiry on Wednesday November 28 at 7 pm or McMaster University on the evening of November 27th. The McMaster event is sponsored by the McMaster Association of Secular Humanists.

For more information see [Evolution Is a Theory and a Fact with Prof. Laurence Moran].

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