Hans Adolf Krebs (2)

Hans Adolf
By: Victoria Sendanyoye, Carter
Beaupre-Mcphee and Iyoma
 About Hans Adolf Krebs
 Prior knowledge of metabolic reactions
 Krebs’ experimental design
 Observations and Results
 Interpretation of the results
 Conclusion and major discovery
 Efficiency of Krebs’ Cycle
History: Hans Krebs (1900-1981)
German physician and biochemist
Identified two important metabolic processes: the urea cycle
(ornithine cycle) and the citric acid cycle, which was
discovered in 1937 (Ref. 2 Helmenstine)
Earned a Noble Prize for the citric acid cycle (Krebs’ cycle) in
He taught at Cambridge and at the University of Sheffield and
after 1954 was a professor of biochemistry at Oxford (Ref. 6
"Krebs, sir hans," 2007)
Krebs Cycle was originally known as the tricarborxylic acid
History: Knowledge of Metabolic
Processes (Early 1900’s)
Progress was made in the study of fermentation
Very little was known about the oxidization of sugar in living cells
In 1935, biochemist Albert Szent-Gyorgyi was able to describe
the sequence of reactions of succinate oxidation, specifically
succinate to fumarate to malate to oxaloacetate (dicarborxylic
It was confirmed that the organic acids act as cataylsts
Martius and Knoop discovered another part of the sequence. That
is, citrate to isocitrate to alpha-ketoglutarate to succinate
(tricarboxylic acids) (Ref. 1 Caprette)
Krebs’ Experimental Design
Independent Variable: Malonate (competitive inhibitor of the
enzyme succinate dehydrogenase)
Dependent Variable: Accumulation of succinate
Controlled variables: type and amount of muscle tissue
(minced or grinded pigeon breast muscle), type and amount of
competitive inhibitor, and amount of the organic acids.
Malonate was added to muscle suspensions in aqueous
solutions in the presence of the dicarboxylic and tricarboxylic
acids (Ref. 3 Krebs, 1953)
Observations and Results
When the malonate was added to the muscle suspension in
the presence of these organic acids, there was major
accumulation of succinate (Ref. 1 Caprette)
This also inhibited the oxidation of the pyruvate since there
was a limited amount of oxaloacetate
In the uninhibited system, one oxaloacetate molecule could
oxidize many pyruvates
In the poisoned system, only one pyruvate could be oxidized
per one oxaloacetate molecule
Surprise breakthrough! Citrate was readily formed in muscle
provided that oxaloacetate was present (Ref. 3 Krebs, 1953)
Interpretation of the Results
The fact that malonate inhibited the entire sequence of the
reactions when it was added to each of the organic acids
indicated that the sequence was cyclic (Ref. 1 Caprette)
It also indicated that succinate and succinate dehydrogenase are
essential components in the enzymatic reactions
Some citrate and alpha-ketoglutarate accumulated as well which
suggested that they are produced before succinate
It was assumed that the formation of citrate from oxaloacetate
occurred as a result of the oxaloacetate condensing with a
substance derived from a carbohydrate, such as pyruvate or
acetate (Ref. 3 Krebs, 1953)
Conclusion and Major discovery (1937)
The discovery of the synthesis of
citrate from oxaloacetate
completed the scheme of
carbohydrate oxidation (Ref. 1
This concept explained the catalytic
nature of the di- and tricarboxylic
acids and their ability to oxidize in
tissues that oxidize carbohydrates,
as well as fatty acids, and amino
Years later, the citric acid cycle was
found to function in the tissues of
aerobic plants and micoorganisms
( Ref. 7 "The citric acid,").
Original citric acid cycle
The Efficiency of the Citric Acid Cycle
The details of the citric acid cycle were worked out by the study
of highly purified enzymes of the cycle
Some questioned whether these enzymes really did function in a
cycle in living cells and whether the rate was high enough to
account for all the glucose oxidation in animals
Metabolites such as pyruvate and acetate were isotopically
labeled with 13C or 14C and were traced throughout the pathway
of the citric acid cycle (isotope tracer technique)
It was confirmed that it does take place in living cells and that it
does occur at a high rate ( Ref. 7 "The citric acid,")
Caprette, D. (n.d.). Hans krebs (1900-1981). Retrieved from
Helmenstine, A. (n.d.). Overview of the citric acid cycle. Retrieved from
Krebs, H. (1953, December 11). The citric acid cycle. Retrieved from
Wilson, B. A., Schisler, J. C., & Willis, M. S. (2010). Sir Hans Adolf Krebs:
Architect of Metabolic Cycles. Lab Medicine, 41, 377-380.
No author (n.d.). Hans_Krebs_Citric_Acid. Oxford University Press homepage. Retrieved October 17, 2012, from
Krebs, sir hans adolf. (2007). Retrieved from
The citric acid cycle. (n.d.). Retrieved from
The citric acid cycle. (n.d.). Retrieved from

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