Heinrich Otto Wieland (1877-1957)

German organic chemist awarded a Nobel prize 1930 for his investigations of the constitution of the bile acids and related substances.

Clinically, measurement of serum bile acids can be important to veterinarians as a screening tool for hepatobiliary function. Normally, animals will produce bile acids from cholesterol in their liver and store it in their gall bladder. Bile salts are formed in the hepatocytes by a series of enzymatic steps that convert cholesterol to cholic or chenodeoxycholic acids. The rate limiting step is hydroxylation at the 7-alpha position. These reactions include the activity of 8 enzymes belonging to either monooxygenase or dehydrogenase enzyme classes. These acids are then conjugated with glycine or taurine and secreted as Na+ (or K+) salts. Conjugation causes a decrease in their pKa values, making them more water soluble.

The bile acids will then be released into the small intestine via the bile duct during intestinal contraction and play an integral role in the absorption of dietary lipids and lipid soluble vitamins. In most species, more than 90% of the bile salts are actively reabsorbed (by a sodium-dependent co-transport process) from the ileum into the hepatic-portal circulation from where they are cleared and resecreted by the liver to once again be stored in the gall bladder. This secretion/reabsorption cycle is called the Enterohepatic Circulation.

Enterohepatic Recirculation:

Large amounts of bile acids are secreted into the intestine every day but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum. Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this Enterohepatic Recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase. It should be noted that liver disease can dramatically alter this pattern of recirculation, for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assays of systemic levels of bile acids such as Bile Acids-L₃K^? are used clinically as a sensitive indicator of hepatic disease.

See a full animation of Enterohepatic Circulation

Selected works

Wieland was born in Pforzheim in the Black Forest and attended several universities. He spent most of his career at the University and Technische Hochschule of Munich. During World War I he researched into chemical warfare.
In 1912 Wieland showed that bile acids have similar structures to that of cholesterol. Later he worked out what he thought was the basic skeleton of a steroid molecule (for which he was awarded the Nobel prize), but it was found to be incorrect. In 1932 he and his co-workers produced a somewhat modified structure, which is still accepted today.
Wieland did other work with the bile acids, demonstrating their role in converting fats into water-soluble cholic acids (a key process in digestion). He determined the structures of, and synthesized many, toadstool poisons, such as phalloidine from the deadly Amanita fungus. He also began research into the composition and synthesis of pterins, the pigments that give the colour to butterflies' wings.
Wieland proved experimentally that biological oxidation (the process within living tissues by which food substances such as glucose are converted to carbon dioxide and energy) was in fact a catalytic dehydrogenation. This was in direct opposition to the findings of Otto Warburg, who had shown that biological oxidation was an addition of oxygen, and the controversy sparked debate and research. In the end both dehydrogenation and oxidation were shown to occur.