Henseleit, Kurt

In 1937 Krebs found that citrate could be formed in muscle suspensions if oxaloacetate and either pyruvate or acetate were added. He saw that he now had a cycle, not a simple pathway, and that addition of any of the intermediates could generate all of the others. The existence of a cycle, together with the entry of pyruvate into the cycle in the synthesis of citrate, provided a clear explanation for the accelerating properties of succinate, fumarate, and malate. If all these intermediates led to oxaloacetate, which combined with pyruvate from glycolysis, they could stimulate the oxidation of many substances besides themselves. (Kreb s conceptual leap to a cycle was not his first. Together with medical student Kurt Henseleit, he had already elucidated the details of the urea cycle in 1932.) The complete tricarboxylic acid (Krebs) cycle, as it is now understood, is shown in Figure 20.4. 

In ureotelic organisms, the ammonia deposited in the mitochondria of hepatocytes is converted to urea in the urea cycle. This pathway was discovered in 1932 by Hans Krebs (who later also discovered the citric acid cycle) and a medical student associate, Kurt Henseleit. Urea production occurs almost exclusively in the liver and is the fate of most of the ammonia channeled there. The urea passes into the bloodstream and thus to the kidneys and is excreted into the urine. The production of urea now becomes the focus of our discussion. 

The urea cycle Urea is synthesized in the liver by the urea cycle. It is then secreted into the bloodstream and taken up by the kidneys for excretion in the urine. The urea cycle was the first cyclic metabolic pathway to be discovered by Hans Krebs and Kurt Henseleit in 1932,5 years before Krebs discovered the citric acid cycle (see Topic LI). The overall reaction of the pathway is ... 

In terrestrial vertebrates, urea is synthesized by the urea cycle (Figure 23.16). The urea cycle, proposed by Hans Krebs and Kurt Henseleit in 1932, was the first cyclic metabolic pathway to be discovered. One of the nitrogen atoms of the urea is transferred from an amino acid, aspartate. The other nitrogen atom is derived directly from free NH4 +, and the carbon atom comes from HCO3 (derived by hydration of CO2 see Section 9.2). 

In ureotelic organisms the urea cycle disposes of approximately 90% of surplus nitrogen. As shown in Figure 15.1, urea is formed from ammonia, C02, and aspartate in a cyclic pathway referred to as the urea cycle. Because the urea cycle was discovered by Hans Krebs and Kurt Henseleit, it is often referred to as the Krebs urea cycle or the Krebs-Henseleit cycle. 

In 1931 Krebs moved to Freiburg to teach medicine. It was there that he authored (with Kurt Henseleit) his first important paper, which examined liver function in mammals and described how ammonia was converted to urea in liver cells. Krebs also studied the syntheses of uric acid and purines in birds. However, Krebs s research was cut short when the Nazis came to power in 1933. Krebs was Jewish, and he was therefore summarily fired fiom his post. He left Germany for England, taking a position at the School of Biochemistry at Cambridge University at the invitation of Sir Frederick Gowland Hopkins (who had won the 1929 Nobel Prize in medicine). In 1935 Krebs moved to the University of Sheffield to become a lecturer in pharmacology. 

The urea cycle was proposed in 1932 by Hans Krebs and a medical student, Kurt f ] Henseleit, based on their laboratory observations. It was originally called the Krebs-Henseleit cycle. Subsequently, Krebs used this concept of metabolic cycling to explain a second process that also bears his name, the Krebs (or TCA) cycle. 

Citrulline, a non-protein amino acid, was identified independently by Mitsimori Wada in watermelon juice (Wada, 1930) and by Dankwart Ackermann as a product of the degradation of arginine (Ackermann, 1931). Soon afterwards, Hans Krebs and Kurt Henseleit (Krebs and Henseleit, 1932) proposed the first metabolic cycle ever described, in which citrulline was an intermediary in the synthesis of urea. A few years later, the role of aspartate as the donor of the second nitrogen for urea synthesis was established by Sarah Ratner (Ratner and Pappas, 1949). 

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