Biology Reference
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Krebs ( 1953 ; Krebs and Johnson 1937 )—and the transfer of electron from NADH
to molecular O 2 through the respiratory chain to produce water—pioneered by the
discovery of cytochromes that changed their spectroscopic properties in the pres-
ence of O 2 (Keilin 1929 ).
Lipmann ( 1941 ) proposed that ATP is the universal carrier of biological energy
when the phosphate bond energy released from its hydrolysis is used to drive most
biochemical reactions that require energy. However, missing from this picture was
the regeneration of ATP that involves the phosphorylation of ADP with energy
provided by the oxidative breakdown of foodstuffs, hence “oxidative phosphoryla-
tion.” This riddle was solved by the “chemiosmotic hypothesis.” As postulated by
Mitchell ( 1961 ), the “chemiosmotic hypothesis” proposed that the energy released
by respiration is used by the respiratory enzymes to transport protons across the
mitochondrial membranes building up a proton motive force (pmf) composed of an
electric potential and an osmotic component (Mitchell 1961 ). This pmf is used by
the ATP synthase to phosphorylate ADP [see (Weber 2005 ), for a useful historical
and epistemological account]. The system is self-regulated by the availability of
ADP (Chance and Williams 1956 ).
The fact that DNA is the carrier of biological specificity in bacteria was
demonstrated directly by Avery et al. ( 1944 ) and Hershey and Chase ( 1952 ).
Watson and Crick ( 1953 ) introduced the double helix model of the DNA thus
providing a mechanism for self-replication and fidelity; complementary base-
pairing ensured both replication and conservation. However, “indications that
the cell was involved in the maintenance of genetic stability had begun to emerge
from studies of radiation damage in bacteria and bacterial viruses (phages),
especially from the discovery that certain kinds of damage could be spontaneously
reversed” (Fox Keller 2000 ).
The association of the sequence of bases in the DNA and a protein came after the
direct demonstration of the synthesis of a polymer string of the amino acid
phenylalanine from a uniform stretch of nucleic acid consisting of a single nucleo-
tide (uridine) (Nirenberg and Matthaei 1961 ). The central dogma was born; “DNA
makes RNA, RNA makes protein, and proteins make us” (Crick 1957 ).
In 1961 , Jacob and Monod introduced the concept of genetic program , extending
their success, and in analyzing the operon as a mechanism of regulation of enzyme
synthesis in Escherichia coli (Jacob and Monod 1961 ). This provided a more
general description of the role of genes in embryonic development (Fox Keller
2002 ). These investigations led to the proposal of “structural” and “regulatory”
genes thereby locating in the genome the program as a means of controlling its own
execution, i.e., structural genes and regulatory elements are coordinated by the
product of a regulatory gene. At present, the genome sequencing of more than
350 species, including Homo sapiens , and the informational content of genes and
proteins systematized in databases constitute a fertile field for data mining and the
ground work for exploring genetic interrelationships within and between species
and their evolutionary meaning.
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