# Pathway from Sucrose to Cholesterol

I was reading Linus Pauling's book How to Live Longer and Feel Better, and in various places in the book he discusses a correlation between increased sucrose intake and increased blood plasma cholesterol levels, as reported in a study by Milton Winitz.

Pauling writes:

... the metabolism of sucrose yields in it's first step equal amounts of glucose and fructose. ... Fructose metabolism goes in part by a different route such that it produces acetate, which is a precursor of the cholesterol that we synthesize in our liver cells.

I was wondering specifically what the metabolic pathway from sucrose to cholesterol is and given say 100 grams of sucrose, how much will be turned by the body into cholesterol.

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As you have known that metabolism of sucrose yields glucose and fructose.So formed glucose undergoes glycolysis producing pyruvate or lactate(under anaerobic condition). In case of fructose, it is converted into fructose-1-phosphate and which on action of aldolase enzyme produces dihydroxyacetone phosphate and glyceraldehyde-3-phosphate which are the intermediate products of glycolysis and finally converted to pyruvate.

The end product of glycolysis i.e. pyruvate is converted into acetyl coa in presence of coenzyme A , which is the precursor for the synthesis of cholesterol.

For the synthesis of cholesterol , acetyl coa undergoes different enzymatic reactions finally forming cholesterol at the end.

• Any idea what percentage of the sucrose ends up as cholesterol? – Robert S. Barnes Mar 1 '15 at 10:43
• Well it depends on the requirement of glucose in our body. If we have to expense large energy then less cholesterol is formed and viceversa. According to research article jbc.org/content/263/19/9366.full.pdf ,about 20-30% of sucrose is converted to cholesterol in fibroblast cells. – CCR Mar 1 '15 at 10:58
• By the way, what program generated that graph? Or did you scan it? – Robert S. Barnes Mar 1 '15 at 11:15
• Well I found the article online so I am not aware of the inside procedure and instruments used in the research. But they might have really high class and significant instruments for calibrating the data and programs for analysis.. – CCR Mar 1 '15 at 11:20
• I mean the image of the process you used in your answer, how was it created? – Robert S. Barnes Mar 1 '15 at 11:41

Our body uses the so-called "mevalonate" pathway to synthesize cholesterol (and many more related terpenes) from acetate. Sucrose is 12 carbon atoms, acetate is 2. Even if we allow both glucose and fructose to be converted to acetate, which is possible but not commonly attained because of the way metabolism is regulated) we will get only 4 acetate molecules, containing 8 carbon atoms. The other 4 carbons are lost as $\ce{CO2}$.

Cholesterol has 27 carbon atoms. But the pathway for its synthesis goes through lanosterol, which has 30. So each mole of sucrose (which gives rise to 16 carbon-moles of acetate) can make 8/30 = 26.7% mole of cholesterol.

That calculation assumes that only carbon is limiting, and that the emitted $\ce{CO2}$ cannot be recovered. If you relax those assumptions, you can calculate the theoretical yield in more detail. Here is one paper that goes through very similar calculations for production of terpenes.

BTW, some bacteria have a different pathway for terpene biosynthesis that has a higher theoretical yield, because it doesn't start with acetate, it starts with glycolytic precursors before pyruvate dehydrogenase. This completely different pathway is called the DXP pathway (or the MEP pathway or the non-mevalonate) pathway.

• So given your number of a theoretical maximum of 26.7% of the sucrose being converted to cholesterol is CCR's comment that a study showed between 20 to 30% being converted sound reasonable to you? – Robert S. Barnes Mar 1 '15 at 19:50
• Since 26.7 is between 20 and 30, yeah, sounds reasonable to me! – Curt F. Mar 2 '15 at 4:12