Biographical Memoirs: Volume 69 (1996)

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HARLAN D GOFF WOOD September 2, ~ 907-September I 2, ~ 99' BY DAVID A. GOLDTHWAIT AND RI C HARD W. HAN S O N HARLAND GOFF WOOD, WHO was clescenclec! from William Goffe (b. 1619), one of the appointee! judges respon- sible for the beheading of King Charles I, was born on September 2, 1907, in the small town of Delavan, Minne- sota. His parents, both of whom hac! only a high school education, taught their four sons en c! one daughter to work hare! en c! to be self-reliant the result for the sons: two Ph.D.s, one Ph.D.-M.D., one M.D., en c! one LL.B, en c! for the daughter: an honorary LL.D. It is h are! to picture HarIanc! Wool! as a frail chiTc! who spent two years in kindergarten and two years in the first grade. He and his brothers helped on the family's farm in Mankato, Minnesota, walking the mile home from school at noon to water the stock en c! then running back after lunch. At Macalester College in Minne- sota, he majorec! in chemistry en c! there met Milcirec! Davis, whom he marries! in 1929. In 1931 he was acceptec! as a graduate student in bacteriology at Iowa State University at Ames by C. H. Werkman, who was starting to investigate the chemistry of bacterial fermentations. It was there that Harianc! made his stunning discovery of CO2 fixation, which up to that time was known to occur only in chemosynthetic en c! photosynthetic autotrophs. This idea was so controversial 395

396 B I O G RA P H I C A L EMOIRS that for some time Professor Werkman cloubtec! the vaTiclity of HarIancl's finclings. From 1935 to 1936 HarIanc! worker! as a fellow with W. H. Petersen at the University of Wisconsin, en c! it was here that he joiner! Ec! Tatum in studying the growth factor re- quirements for propionibacteria. HarIanc! returnee! to Werkman's department in 1936 to focus on CO2 fixation, as will be cliscussecI. Although HarIanc! was tremenclously pro- cluctive at Ames, builcling a thermal diffusion column for the isolation of i3C as well as a mass spectrometer to mea- sure the isotope, Werkman wouIc! not initially allow him to work on animals en c! wouIc! not arrange for HarIancl's fu- ture inclepenclence at Ames. An c! so in 1943 he mover! to the Department of Physiological Chemistry at the Univer- sity of Minnesota, en c! it was there that he user! i3C-NaHCO3 labeling of the different carbon atoms of the glucose of rat liver glycogen to study the pathways of glucose synthesis. In 1946 HarIanc! acceptec! the position of chairman of the Department of Biochemistry at the School of Medicine of what was then Western Reserve University in ClevelancI, Ohio, on the condition, as he toIc! Dean Joseph Wearn, that he be allowed! to go cleer hunting with his father en c! four brothers each autumn. He lover! cluck en c! cleer hunt- ing en c! even at seventy-nine years of age was seen 35 feet up a tree waiting for a deer. As chairman he brought in an entirely new faculty that was orientec! to the use of isotopic tracers to stucly a variety of metabolic pathways. Uncler Hariancl's direction, this young en c! energetic group, which included future members of the National Academy of Sci- ences, Merton Utter en c! Lester Krampitz, createc! an out- stancling national reputation for the department. At the local level, he was also unique. HarIanc! instituter! a policy that all honoraria, even for participating in stucly sections, should go into a student travel fund, since he felt that out

HARLAN D G O FF WO O D 397 sicle activities shouic! have an intrinsic value baser! on sci- ence en c! not on money echoes of William Goffe. Depart- mental seminars were at noon on Saturday en c! monthly staff meetings were hell! after that, often until 5:00 p.m., when they were terminatec! by telephone calls from irate wives. There was a pooling of resources, a sharing of all equipment, en c! a camaraderie that wouic! be clifficult to equal in these times. HarIanc! Wool! spent the last forty-five years of his career at Case Western Reserve University (Western Reserve Uni- versity merger! with Case Institute of Technology in 1968~. He retiree! as chairman in 1965 so that he conic! have more time for research, en c! for Harianc! this meant research at the bench, not just at the clesk. He continues! "pouncling the bench," as he caller! it, right up until a few clays before his cleath on September 12, 1991. Lymphoma was cliagnosec! four years before his cleath, he cliec! of a fall that resultec! in a ruptures! spleen. HarIanc! hac! undergone chemothera- peutic cycles several times, but they never significantly halted his scientific activities. At the time of his cleath, he hell! three grants from the National Institutes of Health, hac! a working group of fifteen associates, en c! was writing nine manuscripts. At the last meeting of the ASBMB that he attenclecI, he hac! twelve posters on clisplay en c! was present to discuss results relater! to each of them. Between his sev- entieth birthday en c! his cleath, he publisher! ninety-six pa- pers, all in well-respectec! journals surely a recorc! for an "elclerly" biochemist. He is survives! by his wife MiTcirec! en c! two daughters. HarIanc! Wool! left a long en c! clistinguishec! recorc! in the life sciences, beginning with his pioneering work with C. H. Werkman at Iowa State College, which clemonstratec! for the first time that CO2 is utilizer! in heterotrophic or- ganisms. In 1935 he demonstrated that the prevailing dogma

398 B I O G RA P H I C A L EMOIRS that CO2 was utilizer! only by bacterial autotrophs was in- correct. In a series of studies he cleterminec! the products former! from the fermentation of glycerol by propionic acid bacteria in a bicarbonate buffer system en c! caTculatec! the carbon en c! oxiciation-recluction balances to account for the carbon of the fermented substrate en c! to ensure that there was a balance of the oxiciation-recluction state of substrates en c! products. Surprisingly, more carbon was fount! in the products than was supplied by the fermented glycerol. He subsequently cliscoverec! that the extra carbon was clerivec! from CO2 in the buffer en c! that oxidation balances! recluc- tion when the recluction of CO2 was taken into account. He proposer! that CO2 en c! pyruvate combiner! to form oxa- lacetate, which subsequently was reclucec! to succinate. This pyruvate-CO2 reaction became known as the WoocI-Werkman reaction. When isotopic tracers of carbon became available in the late 1930s, HarIanc! was among the first to exploit isotopes in biological studies. He was a true pioneer in cleveloping procedures for the use of these isotopes for metabolic tracer studies. As previously noted, he built a water-coolec! ther- mal diffusion column in a five-story elevator shaft for the separation of i3C isotopic carbon. HarIand was always fond of describing the day that he found the column warped en c! clistortec! clue to a temporary cirop in the water pres- sure. This cirop, he finally cliscoverecI, occurrec! when the home economics class let out en c! three toilets were flusher! simultaneously! To measure i3C, he also built a mass spec- trometer. His innovative work initially proviclec! evidence that citrate was not part of the citric acid cycle because he hac! assumer! that citrate was a symmetrical molecule. In his characteristic manner, he later sail! in a Lynen Lecture that even though he was wrong it was one of his "most impor- tant contributions" to biochemistry. The studies by Wool!

HARLAN D G O FF WO O D 399 en c! his colleagues in 1945 clearly clemonstratec! the path- way of CO2 incorporation into specific carbon atoms of glucose clerivec! from hepatic glycogen. HarIanc! gracluatec! briefly from bacteria to cows, where his farm backgrounc! helpec! in the injection of i4C glucose into the artery going to the right udder. Subsequently, by personally milking each sicle, he cleterminec! that lactose was synthesizec! from free glucose rather than glucose-~-phosphate en c! that it was glu- cose that reactec! with UDP-galactose to form lactose. In collaboration with Joseph Katz en c! Bernarc! R. Landau, HarIanc! also clevelopec! methods to estimate the propor- tion of carbohydrate metabolizec! in the Penrose pathway en c! glycolysis by studying i4C distributions in glucose and glycogen. These latter studies were instrumental in estab- lishing the stoichiometry of the Penrose pathway. The overall direction of Hariancl's research over sixty years continues! to be on CO2 fixation. During the last thirty years of his life, he focuses! on establishing the reaction mechanism of transcarboxylase (TC) from propionibacteria. This is a key enzyme in the propionic acid cycle, en c! it transfers a carboxy! group in the conversion of methy~malony! CoA + pyruvate to propiony! CoA + oxalacetate. The en- zyme is also extremely complex, with six iclentical central subunits, each with two CoA-bincling sites, six climeric out- sicle subunits each of the six with two keto acid sites, en c! twelve small biotiny! subunits that carry the carboxy! groups between the CoA and keto sites. The kinetics of the reac- tion clic! not fit the acceptec! mechanisms, so Dexter Northrup, then a student with HarIancI, proposer! a new kinetic mecha- nism for TC that was later verifier! by Northrup en c! WoocI. Extensive work was done on the separation of the three subunits of TC en c! on the reconstitution of enzyme activ- ity. Together with a number of associates, Wool! stucliec! the quaternary structure of TC by electron microscopy, and this

400 B I O G RA P H I C A L EMOIRS reveaTec! the "Mickey Mouse" enzyme. Using thin crystals of the enzyme, resolution of the structure at 10 A was possible by microscopy. The primary amino acid sequence of the biotiny! subunit was cleterminecI, and, in collaboration with Davic! Samols, the genes for all three subunits were clones! en c! sequenced. At the enc! of his life, HarIanc! was studying the enzymatic properties of a large number of mutants that were generated in the three different subunits en c! was clo- ing many of the enzyme assays himself. These studies were of great interest because of the complexity of the subunit structure of the enzyme en c! the ability to examine cliffer- ent aspects of function. Harianc! Wool! also cliscoverec! a novel pathway for car- bon monoxide (CO) fixation in acetogens, a group of anaero- bic bacteria that synthesize acetate from CO or CO2/H2. This new pathway of autotrophic growth, clemonstratec! in Ctostridium thermoaceticum en c! Acetobacterium woodii, cliffers from all previously clescribec! pathways for autotrophic growth, such as the Calvin reductive pentose cycle or the tricar- boxylic acid cycle. Much of HarIancl's work in the area was clone in collaboration with Lars Ljunciahl, both at Case West- ern Reserve University and the University of Georgia. The mechanism of this pathway involves recluction of CO2 to methyTtetrahydrofolate and transfer of the me tiny! group to a corrinoid protein. The me tiny! group is then transferred to carbon monoxide clehycirogenase (CODH), CO ant! CoASH/moleties combine with CODH, which catalyzes the formation of acetyI-CoA from the above three groups. Thus, CODH plays a central role in this pathway. Most of the enzymes involves! in the various steps of the pathway were purified to homogeneity. The availability of purified en- zymes permitted HarIanc! en c! his collaborators to dissect the pathway en c! define the role of each enzyme. Detailec! studies towarc! eTuciciating the mechanism of action of CODH

HARLAN D G O FF WO O D 401 were initiated. CODH contains six nickel, three zinc, thirty- two iron atoms, forty-two labile sulficles en c! has three ac- ceptor sites: one for the me tiny! group transferred from the me tiny! corrinoic! enzyme, a CO site, en c! a CoASH site. From ESR studies it was shown that the Ni-Fe center is involves! in the interaction of the CO group with CODH. Also, the me tiny! group is bounc! to a cysteine residue of CODH. The CoASH substrate site has been characterizec! using fluorescence spectroscopy, circular clichroism, en c! chemical mollification. From these studies it was proposer! that both tryptophan (s) en c! arginine (s) are involves! in the bincling of CoASH to CODH. Even from this brief review it is clear that Harianc! Wood, over the sixty years that he was involves! in research, "follower! the trail of CO2." HarIanc! Wool! was also a pioneer in studying the role of pyropnospnate anct po~ypnospnate as energy sources. It has long been acceptec! that the energy container! in the anhy- dride bond of pyrophosphate is not utilized efficiently by cells. However, HariancI, together with Nelson Phillips, shower! this not to be true by the isolation en c! characterization of bacterial enzymes that utilize pyrophosphate in reaction with oxaloacetate, with phosphoenolpyruvate, and with fructose- 6-phosphate. Inorganic polyphosphates have been consicI- erec! by others as primitive sources of energy. HarIanc! ex- tensively stucliec! the enzymatic synthesis of polyphosphate from ATP en c! shower! that a bacterial glucokinase utilizes polyphosphate much more effectively than ATP in the reac- tion with glucose. Two separate sites exist on the enzyme for these two sources of high-energy phosphate. This en- zyme may represent an intermediate stage of evolution from a polyphosphate-dependent metabolism to an ATP-depen- clent metabolism. HarIand Wood's outstanding career was marked by many innovations. However, what most characterizes! Harianc! was

402 B I O G RA P H I C A L EMOIRS his scientific style. He was remarkable for several reasons. First, one conic! always feel the sense of excitement en c! drive that he brought to the experimental aspect of sci- ence. The focus of the excitement was always on discovery. Second, he continually clevelopec! en c! applier! the latest technology to his experimental problem. There were many jumps from fermentation balances all the way to gene se- quencing. Finally, he was able to collaborate with others very procluctively, particularly those with expertise in spe- cific areas where the scientific results conic! not have been achiever! by either group alone. The flavor of the man en c! . his approach to science are best captures! by HarIanc! him- self in his autobiography in the Annual Review of Biochemis- try in 1985. HarIanc! Woocl's outstanding career was market! by many innovations in other areas. As chairman of the biochemis- try department at Western Reserve University, he lee! the curriculum reform that resultec! in an integrates! organ- system-basec! methoc! for teaching the first two years of mecli- cal school, this curriculum has had a great impact on medi- cal education nationally. He swayer! the faculty to vote for the new curriculum with the challenge, "How clo you guys know it's not going to work unless you run the experiment?" He served as chairman of the biochemistry department for twenty years, as clean of sciences at Case Western Reserve University from 1967 to 1969, en c! finally as university pro- fessor en c! university professor emeritus from 1970 to 1991. Harianc! Wool! was president of the American Society of Biological Chemistry from 1959 to 1960. First as secretary- general en c! then as president of the International Union of Biochemistry in 1982-83, he clic! a great clear for that organization's revitalization. He served on many study sec- tions, en c! his strong support for younger biochemists clur- ing his tenure on one of those stucly sections became known

HARLAN D G O FF WO O D 403 as "The Wood Factor." He was a member of many advisory boards and served as an editorial board member of a num- ber of important journals. As a young member of the Edito- rial Board of the Journal of Biological Chemistry, he was in- strumental in eliminating self-perpetuating appointments when he resigned after five years and argued, "Listen, if all you guys died tomorrow, a good board could be picked the next day to replace you." He received a number of presti- gious awards, including the Eli Lilly Award, the Car! Neuberg Medal, the Lynen Lecture Medal, the Waksman Award, the Rosenstiel Award, the Michaelson-Morly Award, and the National Medal of Science. He held honorary degrees from MacaTester College, Northwestern University, the University of Cincinnati, and Case Western Reserve University. He was a member of the National Academy of Sciences, the Ameri- can Academy of Arts and Sciences, and the Biochemical Society of Japan and served on the President's Science Ad- visory Committee under Presidents Johnson and Nixon. In a 1985 Annual Review of Biochemistry article, Hariand Wood wrote that "scientists are the fortunate few who earn a livelihood by pursuit of a hobby. This hobby sometimes consumes their every thought, but usually it provides a deeply satisfying life." He continued, "Many highly successful sci- entists desert the laboratory bench early in their careers and thereafter direct the research of their co-workers. My goal has been to remain personally active in the laboratory as long as I am involved in science." And so he did. Over the sixty years that flarland Wood spent in science, he made countless friends in many countries who revered him not just for his accomplishments but for his intellec- tual honesty. Here was a man without pretensions, whose opinions and decisions were always based on principles and ~ . ~ ~ ~ . ~ not on personal factors, a man whose mind was open to new ideas and concepts, a man who by his example and

404 BIOGRAPHICAL MEMOIRS encouragement got the best out of his associates, en c! a man who, once he macle up his mincI, wouIc! drive straight towarc! his goal. In him one felt the warmth, strength, en c! integrity that macle him unique en c! irreplaceable.

HARLAN D G O FF WO O D SELECTED BIBLIOGRAPHY 1933 405 With O. L. Osburn and C. H. Werkman. Determination of formic, acetic and propionic acids in a mixture. Ind. Eng. Chem. Analyt. Ed. 5:247-50. 1934 With C. H. Werkman. The propionic acid bacteria: On the mecha- nism of glucose dissimilation. 7. Biol. Chem. 105:63-72. With C. H. Werkman. Pyruvic acid in the dissimilation of glucose by the propionic acid bacteria. Biochem. I. 28:745-47. With C. H. Werkman. Intermediate products of the propionic acid fermentation. Proc. Soc. Exp. Biol. Med. 31:938-40. With C. H. Werkman. The utilization of agricultural by-products in the production of propionic acid by fermentation. 7. Agric. Res. 49:1017-20. 1935 With C. H. Werkman. The utilization of CO2 by the propionic acid bacterial in the dissimilation of glycerol. 7. Bacteriol. 30:332 (Ab- stract) . With C. H. Werkman. The isolation and possible intermediary role of formaldehyde in the propionic acid fermentation. 7. Bacteriol. 30:652-53. 1936 With C. H. Werkman. The utilization of CO2 in the dissimilation of glycerol by the propionic acid bacteria. Biochem. I. 30:48-53. With C. H. Werkman. Mechanism of glucose dissimilation by the propionic acid bacteria. Biochem. I. 30:618-23. With R. W. Stone and C. H. Werkman. Activation of the lower fatty acids by propionic acid bacteria. Biochem. I. 30:624-28. With C. Erb and C. H. Werkman. A macro-respirometer for the study of aerobic bacterial dissimilation. Iowa State Colt. I. Sci. 10:295- 302. With C. Erb and C. H. Werkman. The aerobic dissimilation of lactic acid by the propionic acid bacteria. 7. Bacteriol. 31:595-602.

406 B I O G RA P H I C A L EMOIRS With O. L. Osburn and C. H. Werkman. Determination of volatile fatty acids by the partition method. Ind. Eng. Chem. Analyt. Ed. 8:270-75. With E. L. Tatum and W. H. Peterson. Growth factors for bacteria. V. Vitamin Bit: a growth stimulant for propionic acid bacteria. Biochem. I. 30:1898-1904. With E. L. Tatum and W. H. Peterson. Essential growth factors for the propionic acid bacteria. II. Nature of the Neuberg precipi- tate fraction of potato. 7. Bacteriol. 32:167-74. 1937 With A. A. Anderson and C. H. Werkman. Growth factors for the propionic and lactic acid bacteria. Proc. Soc. Exp. Biol. Med. 36:217- 19. With C. Erb and C. H. Werkman. Dissimilation of pyruvic acid by the propionic acid bacteria. Iowa State Colt. I. Sci. 11:287-92. With R. W. Stone and C. H. Werkman. The intermediate metabo- lism of the propionic acid bacteria. Biochem. I. 31:349-59. With E. L. Tatum and W. Peterson. Growth factors for bacteria. IV. An acidic ether soluble factor essential for growth of propionic acid bacteria. 7. Bacteriol. 33:227-42. With C. H. Werkman and R. W. Stone. The dissimilation of phos- phate esters by the propionic acid bacteria. Enzymologia 4:24-30. 1938 With A. A. Anderson and C. H. Werkman. Nutrition of the propi- onic acid bacteria. 7. Bacteriol. 36:201-13. With C. H. Werkman. The utilization of CO2 by the propionic acid bacteria. Biochem. I. 32: 1262-71. With W. P. Wiggert and C. H. Werkman. The fermentation of phos- phate esters by the propionic acid bacteria. Enzymologia 2:373-76. 1939 With R. W. Brown and C. H. Werkman. Nutrient requirements of butyric acid butyl alcohol bacteria. J. Bacteriol. 38:631-40. 1940 With C. R. Brewer, M. N. Mickelson, and C. H. Werkman. A

HARLAN D G O FF WO O D 407 macrorespirometer for the study of the aerobic metabolism of microorganism. Enzymologia 8:314-17. With C. Geiger and C. H. Werkman. Nutritive requirements of the heterofermentative lactic acid bacteria. Iowa State Coll. ]. Sci. 14:367- 78. With C. H. Werkman. The fixation of CO2 by cell suspensions of Propionibacterium pentesaceum. Biochem. ]. 34: 7-14. With C. H. Werkman. The relationship of bacterial utilization of CO2 to succinic acid formation. Biochem. ]. 34:129-38. With C. H. Werkman. Gewinnung-Freigelester Enzyme Specialmethoden fur Bakterien Die Methoden der Fermentforschung, ed. Oppenheimer. Leipzig: George Thiem. With C. H. Werkman, A. Hemingway, and A. O. Nier. Heavy carbon as a tracer in bacterial fixation of CO2. 7. Biol. Chem. 135:789-90. 1941 With H. D. Slade, A. O. Nier, A. Hemingway, and C. H. Werkman. Note on the utilization of carbon dioxide by heterotrophic bacte- ria. Iowa State Coll. ]. Sci. 15: 339-41. With C. H. Werkman, A. Hemingway, and A. O. Nier. Position of carbon dioxide-carbon in propionic acid synthesized by Propionibacterium. Proc. Soc. Exp. Biol. Med. 46:313-16. With C. H. Werkman, A. Hemingway, and A. O. Nier. Note on the degradation of propionic acid synthesized by Propionibacterium. Iowa State Coll. ]. Sci. 15:213-14. With C. H. Werkman, A. Hemingway, and A. O. Nier. Mechanism of fixation of carbon dioxide in the Krebs cycle. 7. Biol. Chem. 139:483- 84. With C. H. Werkman, A. Hemingway, and A. O. Nier. Heavy carbon as a tracer in heterotrophic carbon dioxide assimilation. 7. Biol. Chem. 139: 365-76. With C. H. Werkman, A. Hemingway, and A. O. Nier. Heavy carbon dioxide in succinic acid synthesized by heterotrophic bacteria. 7. Biol. Chem. 139:377-81. With C. H. Werkman, A. Hemingway, A. O. Nier, and C. G. Stuckwisch. Reliability of reactions used to locate assimilated carbon in pro- pionic acid. 7. Am. Chem. Soc. 2140-42.

408 B I O G RA P H I C A L 1942 EMOIRS Criteria for experiments with isotopes. In Symposium on the Respira- tory Enzymes and the Biological Action of Vitamins, ed. E. A. Evans, Jr., pp. 252-56. Chicago: University of Chicago Press. With H. D. Slade, A. O. Nier, A. Hemingway, and C. H. Werkman. Assimilation of heavy carbon dioxide by heterotrophic bacteria. I. Biol. Chem. 143:133-45. With C. H. Werkman. On the metabolism of bacteria. Bot. Rev. 8:1- 68. With C. H. Werkman. Heterotrophic assimilation of carbon diox- ide. Adv. Enzymol. 2:135-82. With C. H. Werkman, A. Hemingway, and A. O. Nier. Fixation of carbon dioxide by pigeon liver in the dissimilation of pyruvic acid. 7. Biol. Chem. 142:31 -45. 1943 With G. Kalnitsky and C. H. Werkman. CO2-fixation and succinic acid formation by a cell-free enzyme preparation of Escherichia colt. Arch. Biochem. 2:269-81. With L. O. Krampitz and C. H. Werkman. Enzymatic fixation of carbon dioxide in oxalacetate. 7. Biol. Chem. 147:243-53. 1944 Metabolism of nervous tissue in poliomyelitis. Lancet 64:240-42. With R. W. Brown and C. H. Werkman. Fixation of carbon dioxide in lactic acid by Clostridium butylicum. Arch. Biochem. 5:423-33. With R. W. Brown, C. H. Werkman, and C. G. Stuckwisch. The degradation of heavy-carbon butyric acid from butyl alcohol fer- mentation. 7. Am. Chem. Soc. 66:1812-18. With I. I. Rusoff and J. M. Reiner. Anaerobic glycolysis of the brain in experimental poliomyelitis. J. Exp. Med. 81:151-59. 1945 With R. W. Brown and C. H. Werkman. Mechanism of the butyl alcohol fermentation with heavy carbon acetic and butyric acids and acetone. Arch. Biochem. 6:243-60. With N. Lifson and V. Lorber. The position of fixed carbon in glucose from rat liver. 7. Biol. Chem. 159:475-89. With V. Lorber and N. Lifson. Incorporation of acetate carbon into .

HARLAN D G O FF WO O D 409 rat liver glycogen by pathways other than carbon dioxide fixa- tion. I. Biol. Chem. 161:411-12. With I. I. Rusoff. The protective action of trypan red against infec- tion by a neurotropic virus. 7. Exp. Med. 82:297-309. With M. F. Utter. Fixation of carbon dioxide in oxalacetate by pi aeon liver. 7. Biol. Chem. 160:375-76. With M. F. Utter and T. M. Reiner. Measurement of anaerobic glyco- lysis of brain as related to poliomyelitis. 7. Exp. Med. 82:217-26. With M. F. Utter and T. M. Reiner. Anaerobic glycolysis in nervous . tissue. 7. Biol. Chem. 161:197-217. With B. Vennesland and E. A. Evans. The mechanism of carbon dioxide fixation by cell-free extracts of pigeon liver: distribution of labeled carbon dioxide in the products. 7. Biol. Chem. 159:153- 58. 1946 The fixation of carbon dioxide and the interrelationships of the tricarboxylic acid cycle. Physiol. Rev. 26: 198-246. With V. Lorber, N. Lifson, and T. Barcroft. The metabolism of elate by the completely isolated mammalian heart investigated with carboxyl labeled acetate. Am. I. Physiol. 145:557-60. With M. F. Utter. The fixation of carbon dioxide in oxalacetate by pigeon liver. 7. Biol. Chem. 164:455-76. 1948 Tracer studies on the intermediary metabolism of carbohydrates. In Symposium on the Use of Isotopes in Biology and Medicine, pp. 209-42. Madison: University of Wisconsin Press. The synthesis of liver glycogen in the rat as an indicator of interme- diary me tabolism. Cold Spring Harbor Symp. Quant. Biol. 13:201 -10. With N. Lifson, V. Lorber, and W. Sakami. The incorporation of acetate and butyrate carbon into rat liver glycogen by pathways other than carbon dioxide fixation. 7. Biol. Chem. 176:1263-84. 1949 Tracer studies on the intermediary metabolism of carbohydrates. In Isotopes in Biology and Medicine. Madison: University of Wisconsin Press.

410 B I O G RA P H I C A L EMOIRS With V. Lorber. Carbohydrate metabolism. Ann. Rev. Biochem. 18:299- 334. With W. Shreeve, V. Fell, and V. Lorber. The distribution of fixed radioactive carbon in glucose from rat liver glycogen. 7. Biol. Chem. 177:679-82. 1950 Symposium on chemical transformation of carbons in photosynthe- sis. Fed. Proc. 9:553-55. A consideration of some reactions involving CO2 fixation. Symp. Soc. Exp. Biol. 5:9-28. With V. Lorber, N. Lifson, and W. Sakami. Conversion of propi- onate to liver glycogen in the intact rat, studied with isotopic propionate. 7. Biol. Chem. 183:531-38. With V. Lorber, N. Lifson, W. Sakami, and W. W. Shreeve. Conver sion of lactate to liver glycogen in the intact rat studied with isotopic lactate. 7. Biol. Chem. 183:517-29. With H. T. Strecker and L. O. Krampitz. Fixation of formic acid in pyruvate by a reaction not utilizing acetyl phosphate. 7. Biol. Chem. 182:525-40. 1951 A study of acetone metabolism using glycogen and serine as indica- tors and the roles of C~-compounds in metabolism. In Ciba Foun- dation Conference on Isotopes in Biochemistry, ed. G. E. W. Wolstenholme, pp. 227-45. London: Churchill. With M. F. Utter. Mechanisms of fixation of CO2 by heterotrophs and autotrophs. Adv. Enzymol. 12:41-151. 1952 The metabolism of formate by animals. Harvey Lect. Ser. 14:127-48. A study of CO2-fixation by mass determination of the types of i3C- acetate. 7. Biol. Chem. 194:905-31. Fermentation of 3,4-Ci4 and 1-Ci4-labeled glucose by Clostridium thermoaceticum. J. Biol. Chem. 199:579-83. 1953 With F. W. Leaver. CO9 turnover in the fermentation of 3,4,5 and 6 -

HARLAN D G O FF WO O D 411 carbon components by the propionic acid bacteria. Biochim. Biophys. Acta 12:207-22. With F. W. Leaver. Evidence from fermentation of labeled substrates which is inconsistent with present concepts of the propionic acid fermentation. 7. Cell. Comp. Physiol. 41:225-40. 1954 With G. Popjak. Biological asymmetry of glycerol and formation of asymmetrically labeled glucose. 7. Biol. Chem. 206:875-82. With P. Schambye. The in vivo conversion of i4C-glycerol into rat liver glycogen. In Radioisotope Conference, vol. 1, pp. 346-50. 1955 Significance of alternate pathways in the metabolism of glucose. Physiol. Rev. 35:841-59. With I. A. Bernstein, K. Lentz, M. Maim, and P. Schambye. Degra- dation of glucose Ci4 with Leuconostoc mesenteroides: alternate pathways and tracer patterns. 7. Biol. Chem. 215:137-52. With R. G. Kulka and N. L. Edson. Fermentation of glucose-l-Ci4 in cell-free extracts of Propionibacteria. Proc. Univ. Otago 33:24-25. With F. W. Leaver and R. Stjernholm. The fermentation of three carbon substrates by Clostridium propionicum and Propionibacterium. 7. Bacteriol. 70:521-30. With K. Lentz. Synthesis of acetate from formate and carbon diox- ide by Clostridium thermoaceticum. f. Biol. Chem. 215:645-54. With R. Stjernholm and F. W. Leaver. The metabolism of labeled glucose by the propionic acid bacteria. 7. Bacteriol. 70:510-20. 1956 The teaching of biochemistry in an integrated medical curriculum. Fed. Proc. 15: 865-70. With R. G. Kulka and N. L. Edson. The metabolism of i4C-glucose in an enzyme system from Propionibacterium. Biochem. f. 63:177-82. With R. Stjernholm and F. Leaver. The role of succinate as a pre- cursor of propionate in the propionic acid fermentation. 7. Bacteriol. 72:142-52.

412 B I O G RA P H I C A L 1957 EMOIRS rl ransactions of the Third Conference of Polysaccharides in Biology. New York: Josiah Macy, Jr. Foundation. With I. A. Bernstein. Determination of isotopic carbon patterns in carbohydrate by bacterial fermentation. Methods Enzymol. 4:561- 83. With H. Gest. Determination of formate. In Methods in Enzymology, vol. 3, ed. S. Colowick and N. Kaplan, pp. 285-92. New York: Academic Press. With P. Schambye and M. Kleiber. Lactose synthesis. I. The distri- bution of C14 in lactose of milk after intravenous injection of C14 compounds.~7. Biol. Chem. 226:1011-21. With P. Schambye and G. J. Peeters. Lactose synthesis. II. The dis- tribution of C14 in lactose of milk from perfused isolate cow ud- der.~7. Biol. Chem. 226:1023-34. With P. M. L. Sin and P. Schambye. Lactose synthesis. III. The distribution of C14 in lactose of milk after intra-arterial injection of acetate-l-Cl4. Arch. Biochem. Biophys. 69:390-404. 1958 [racer studies on the synthesis of milk constituents. In Proceedings 2nd International Conference on Peaceful Uses of Atomic Energy, pp. 50-57. New York: Pergamon Press. With R. Gillespie, S. Joffee, R. G. Hansen, and H. Hardenbrook. Lactose synthesis. V. C14 in lactose, glycerol and serine as indica- tors of the triose phosphate isomerase reaction and pentose cycle. ~7. Biol. Chem. 233:1271-78. With J. Katz. The distribution of C14 in the hexose phosphates and the effect of recycling in the pentose cycle.~7. Biol. Chem. 233:1279- 82. With S. H. Pomerantz. A mass analysis study of formaldehyde fixa- tion and cleavage of lactate bv Pro1aionibacterium arabinosum. 7. Biol. Chem. 231 :519-31. J 1 With S. Joffe, R. Gillespie, R. G. Hansen, and H. Hardenbrook. Lactose synthesis. IV. The synthesis of milk constituents after unilateral injection of glycerol-1,3-C14. ~7. Biol. Chem. 233:1264-70. With R. L. Stjernholm. Differential degradation of D- and L- glyc- erol-l-Cl4 by A. aerogenes. Arch. Biochem. Biophys. 78:28-32.

HARLAN D G O FF WO O D 1959 413 With R. Gillespie, R. G. Hansen, W. A. Wood, and H. Hardenbrook. Arteriovenous i4CO2 differences and the pentose cycle in the cow's udder. Biochem. f. 73:694-701. With P. M. L. Sin. Conversion of galactose and glucose to liver glycogen in vivo. f. Biol. Chem. 234:2223-26. 1960 With J. Katz. The use of glucose-Ci4 for the evaluation of the path- ways of glucose metabolism. 7. Biol. Chem. 235:2165-77. With R. L. Stjernholm. Trehalose and fructose as indicators of me- tabolism of labeled glucose by the propionic acid bacteria. 7. Biol. Chem. 235:2753-61. With R. L. Stjernholm. Glycerol dissimilation and the occurrence of symmetrical three-carbon intermediate in the propionic acid fer- mentation. 7. Biol. Chem. 235:2757-61. With R. W. Swick. The role of transcarboxylase in propionic acid fermentation. Proc. Natl. Acad. Sci. U.S.A. 46:28-41. 1961 Tracer studies on the mechanism of carbohydrate metabolism. In Symposium on the Use of Radioisotopes in Animal Biology and the Medi- cal Sciences, pp 193-203. New York: Academic Press. With L. G. Ljungdahl, E. Racker, and D. Couri. Formation of un- equally labeled fructose-6-phosphate by an exchange reaction cata- lyzed by transaldolase. 7. Biol. Chem. 236:1622-25. With P. M. L. Sin and R. L. Stjernholm. Fixation of CO2 by phos- phoenolpyruvic carboxytrans-phosphorylase. 7. Biol. Chem. 236:PC21- 22. With R. L. Stjernholm. Transcarboxylase. II. Purification and prop- erties of methylmalonyl-oxalacetic transcarboxylase. Pro c. Natl. Acad. Sci. U.S.A. 47:289-303. With R. L. Stjernholm. Methylmalonyl isomerase. II. Purification and properties of the enzymes from Propionibacteria. Proc. Natl. A cad. Sci. U.S.A. 47:303-13. 1962 With R. G. Hansen, G. J. Peeters, B. Jacobson, and J. Wilken. Lac

414 B I O G RA P H I C A L EMOIRS lose synthesis. VI. Labeling of lactose precursors by glycerol-1,3- Ci4 and glucose-2-Ci4. 7. Biol. Chem. 237:1034-39. With R. W. Kellermeyer. Methylmalonyl isomerase: a study of the mechanism of isomerization. Biochemistry 1:1124-31. With I. A. Rose, R. W. Kellermeyer, and R. L. Stjernholm. The distribution of Ci4 in glycogen from deuterated glycerol-Ci4 as a measure of the effectiveness of triosephosphate isomerase in viva. 7. Biol. Chem. 237:3325-31. With P. M. L. Siu. Phosphoenolpyruvic carboxytransphosphorylase, a CO2 fixation enzyme from propionic acid bacteria. 7. Biol. Chem. 237:3044-51. With R. L. Stjernholm. Assimilation of carbon dioxide by heterotrophic organisms. In The Bacteria: A Treatise on Structure and Function, ed. I. Gunsalus and R. Stanier. New York: Academic Press. 1963 With S. H. Allen, R. Kellermeyer, R. L. Stjernholm, and B. Tacobson. The isolation, purification and properties of methylmalonyl racemase. 7. Biol. Chem. 238:1637-42. With S. H. Allen and R. L. Stjernholm. The noninvolvement of the ureido carbon of biotin in transcarboxylation. 7. Biol. Chem. 238:PC2889-91. With S. H. Allen, R. L. Stjernholm, and B. Tacobson. Transcarboxylase purification and properties of methyl-malonyl-oxaloacetic trans- carboxylase containing tritiated biotin. 7. Biol. Chem. 238:547-56. With T. Katz. The use of Ci402 yields from glucose-1- and 6-Ci4 for the evaluation of the pathways of glucose metabolism. J. Biol. Chem. 238:517-23. With T. Katz and B. R. Landau. Estimation of pathways of carbohy- drate metabolism. Biochem. Z. 338:809-47. With H. Lochmuller, C. Riepertinger, and F. Lynen. Transcarboxylase. IV. Function of biotin and the structure and properties of the carboxylated enzyme. Biochem. Z. 337:247-66. With R. L. Stjernholm. The symmetrical C3 in the propionic acid fermentation and the effect of avidin on propionate formation. Iowa State Coll. ]. Sci. 38:123-40 1964 With S. H. Allen, R. W. Kellermeyer, and R. L. Stjernholm. Purifica

HARLAN D G O FF WO O D 415 tion and properties of enzymes involved in the propionic acid formation. 7. Bacteriol. 87:171-87. With T. Katz and B. Landau. Evaluation of metabolic pathways of glucose. Abstracts, Sixth International Congress of Biochemistry, vol. 4, pp. 495-96. With R. W. Kellermeyer, S. H. Allen, and R. L. Stjernholm. Methylmalonyl isomerase. IV. Purification and properties of the enzyme from Propionibacteria. f. Biol. Chem. 239:2562-69. With R. W. Kellermeyer, R. L. Stjernholm, and S. H. Allen. Metabo- lism of methylmalonyl-CoA and the role of biotin and BE coen- zymes. Ann. N.Y. A cad. Sci. 112:661-79. With B. Landau, G. Bartsch, and T. Katz. Estimation of pathway contributions to glucose metabolism and the rate of isomeriza- tion of hexose-6-phosphate. 7. Biol. Chem. 239:686-96. 1965 Incorporation of Ci4 from carbon dioxide into sugar phosphates, carboxylic acids and amino acids by Clostridium thermoaceticum. f. Bacteriol. 89: 1055-64. With L. G. Ljungdahl and E. Irion. Total synthesis of acetate from CO2. I. Co-methylcobyric acid and Co-(methyl)-5-methoxy- benzimidazolyl-cobamide as intermediates with Clostridium thermoaceticum. Biochemistry 4:2771-80. With G. T. Peeters, R. Verbeke, M. Lauryssens, and B. Tacobson. Estimation of the pentose cycle in the perfused cow's udder. Biochem. f. 96:607-15. With M. F. Utter. The role of CO2 fixation in metabolism. Essays Biochem. 1:1-27. 1966 With T. T. Davis and H. Lochmuller. The equilibria reactions cata- lyzed by carboxytransphosphorylase, carboxykinase and pyruvate carboxylase and the synthesis of p-enolpyruvate. 7. Biol. Chem. 241 :5692-5704. With L. Li and L. G. Ljungdahl. Properties of nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase from C. thermoaceticum. f. Bacteriol. 92:405-12. With H. Lochmuller and J. J. Davis. Phosphoenolpyruvate carboxy

416 B I O G RA P H I C A L EMOIRS transphosphorylase. II. Crystallization and properties. 7. Biol. Chem. 241 :5678-91. 1967 With L. G. Ljungdahl. The role of corrinoids in the total synthesis of acetate from CO2. In Seventh International Congress of Biochemis- try, Tokyo, Colloqium XII, pp. 549-50. 1968 Mechanism of formation of oxalacetate and phosphoenolpyruvate from pyruvate. 7. Vitamins 14:59-67. With S. H. Allen and R. W. Kellermeyer. Methylmalonyl-CoA racemase from Propionibacterium shermanii. Methods Enzymol. 13:194-98. With T. G. Cooper, T. Tchen, and C. Benedict. The carboxylation of phosphoenolpyruvate and pyruvate. I. The active species of "CO2" utilized by phosphoenolpyruvate carboxykinase, carboxy- transphosphorylase and pyruvate carboxylase. 7. Biol. Chem. 243:3857- 63. With T. T. Davis and T. M. Willard. Phosphoenolpyruvate carboxy- phosphorylase from Propionibacterium shermanii. Methods Enzymol. 13:297-309. With H. Evans. The mechanism of the pyruvate phosphate dikinase reaction. Proc. Natl. Acad. Sci. U.S.A. 61:1448-53. With B. Tacobson, B. Gervin, and D. Northrop. Oxalacetate transcarboxylase from Propionibacterium. Methods Enzymol. 13:215- 31. With R. W. Kellermeyer. 2-methylmalonyl-CoA mutase from Propioni- bacterium shermanii. Methods Enzymol. 13: 207-15. - 1969 With T. G. Cooper, T. Tchen, C. Benedict, and D. Filmer. The species of "CO2" utilized in the carboxylation of P-enolpyruvate and pyruvate. In Chemistry, Biochemistry, and Physiological Aspects, pp. 183-92. Washington: National Aeronautics and Space Admin- istration. With T. T. Davis and T. M. Willard. Phosphoenolpyruvate carboxy- transphosphorylase. III. Comparison of the fixation of CO2 and the conversion of phosphoenolpyruvate and phosphate to pyru- vate and pyrophosphate. Biochemistry 8:3127-36.

HARLAN D G O FF WO O D 417 With T. T. Davis and T. M. Willard. Phosphoenolpyruvate carboxy- transphosphorylase. V. Mechanism of the reaction and role of m e tat i o n s . Biochemistry 8: 3145 -55. With B. Gerwin and B. Tacobson. Transcarboxylase. VIII. Isolation and properties of a biotin-carboxyl carrier protein. Proc. Natl. A cad. Sci. U.S.A. 64:1315-22. With L. G. Ljungdahl. Total synthesis of acetate from CO2 by het- erotrophic bacteria. Ann. Rev. Microbiol. 23:515-38. With D. Northrop. Transcarboxylase. V. The presence of bound zinc and cobalt. 7. Biol. Chem. 244:5801-7. With D. Northrop. Transcarboxylase. VII. Exchange reactions and kinetics of oxalate inhibition. 7. Biol. Chem. 244:5820-27. With I. A. Rose, E. L. O'Connell, P. Noce, M. F. Utter, T. M. Willard, T. G. Cooper, and M. Benziman. Stereochemistry of the enzy- matic carboxylation of phosphoenolpyruvate.7. Biol. Chem. 244:6130- 33. With A. Y. Sun and L. G. Ljungdahl. Total synthesis of acetate from CO2. II. Purification and properties of formyltetrahydrofolate syn- thetase from Clostridium thermoaceticum. I. Bacteriol. 98:842-44. With T. M. Willard and T. T. Davis. Phosphoenolpyruvate carboxy- transphosphorylase. IV. Requirement of metal cations. Biochemis- try 8:3137-44. 1970 With F. Ahmad and B. Tacobson. Transcarboxylase. X. Assembly of active Transcarboxylase from its inactive subunits and incorpora- tion of the biotin-carboxyl carrier protein. 7. Biol. Chem. 245:6486- 88. With B. Tacobson, B. Gerwin, F. Ahmad, and P. Waegell. Trans- carboxylase. IX. Parameters effecting dissociation and reassociation of the enzyme. 7. Biol. Chem. 245:6471-83. 1971 Biochemistry. Fed. Proc. 30:1715-18. With T. G. Cooper. The carboxylation of phosphoenolpyruvate and pyruvate. II. The active species of "CO2" utilized by phospho- enolpyruvate carboxylase and pyruvate carboxylase. 7. Biol. Chem. 246:5488-90.

418 B I O G RA P H I C A L EMOIRS With H. Evans. Purification and properties of pyruvate phosphate dikinase from propionic acid bacteria. Biochemistry 10:721. With R. Ghambeer, M. Schulman, and L. G. Ljungdahl. Total syn- thesis of acetate from CO2. III. Inhibition by alkylhalides of the synthesis from CO2, methyltetrahydrofolate and methyl-B~ 2 by Clostridium thermoaceticum. Arch. Biochem. Biophys. 143:471-84. With R. A. Harte. International structures in science. Fed. Proc. 30:1713- 14. With D. Parker and T. Wu. Total synthesis of acetate from CO2: methyltetrahydrofolate, an intermediate and a procedure for sepa- ration of the folates. 7. Bacteriol. 108:770-76. With M. Schulman. Determination and degradation of microquantities of acetate. Anal. Biochem. 39:505-20. 1972 Some comments about teaching biochemistry. Biochem. Ed. 1:2-3. Transcarboxylase. In The Enzymes, 3rd ea., ed. P. Boyer. pp. 83-113. New York: Academic Press. My life and carbon dioxide fixation. In The Molecular Basis of Biologi- cal Transport, Miami Winter Symposium, vol. 3, pp. 1-54. With F. Ahmad, D. H. Lygre, and B. Jacobson. Transcarboxylase. XII. Identification of the metal-containing subunits of transcarboxylase and stability of the binding. J. Biol. Chem. 247:6299-6305. With N. M. Green, R. C. Valentine, N. H. Wrigley, F. Ahmad, B. Jacobson. Transcarboxylase. XI. Electron microscopy and sub- unit structure. 7. Biol. Chem. 247:6284-98. With M. E. Haberland and T. M. Willard. Phosphoenolpyruvate carboxytransphosphorylase: Study of the catalytic and physical structures. Biochemistry 11 :712-22. With Y. Milner. Isolation of pyrophosphoryl form of pyruvate, phos- phate dikinase from Propionibacteria. Proc. Natl. A cad. Sci. U.S.A. 69:2463-68. With D. J. Parker, R. K. Ghambeer, and L. G. Ljungdahl. Total synthesis of acetate from carbon dioxide. Retention of deute- rium during carboxylation of trideuteriomethyltetrahydrofolate or trideuteriomethylcobalamin. Biochemistry 1 1: 3074-80. With M. Schulman, D. J. Parker, and L. G. Ljungdahl. Total synthe- sis of acetate from CO2. V. Determination by mass analysis of the

HARLAN D G O FF WO O D 419 different types of acetate formed from i4CO2 by heterotrophic bacteria. 7. Bacteriol. 109: 633-44. 1973 The Activities of the International Union of Biochemistry. Informa- tion Bulletin for 9th International Congress of Biochemistry, Stockholm, pp. 13-17. With F. Ahmad, B. Jacobson, N. M. Green, and N. Wrigley. Transcarboxylase: A biotinyl-metallo-enzyme with a unique struc- ture. In Proceedings of 8th Meeting of Federation of European Biochem- istry Society, Enzymes: Structure and Function, vol. 29, pp. 201-16. With R. K. Ghambeer and L. G. Ljungdahl. Total synthesis of ac- etate from CO2. VII. Evidence with Clostridium thermoaceticum that the carboxyl of acetate is derived from the carboxyl of pyruvate by transcarboxylation and not by fixation of CO2. 7. Biol. Chem. 248:6255-61. With W. E. O'Brien and R. Singleton, Jr. Phosphoenolpyruvate carboxytransphosphorylase. An investigation of the mechanism with 180. Biochemistry 12:5247-52. 1974 With W. E. O'Brien. Carboxytransphosphorylase. VIII. Ligand- me- diated interaction of subunits as a possible control mechanism in Propionibacteria. I. Biol. Chem. 249:4917-25. 1975 Appendix VIII to the discovery of carbon dioxide fixation in mam- malian tissues (by Krebs). Mol. Cell. Biochem. 5:91-94. With F. Ahmad, B. Jacobson, M. Chuang, and W. Brattin. Isolation of the subunits of transcarboxylase and reconstitution of the ac- tive enzyme from the subunits. 7. Biol. Chem. 250:918-26. With F. Ahmad, B. Jacobson, M. Chuang, and W. Brattin. Isolation of peptides from the carboxyl carrier subunit of transcarboxylase. Role of the non-biotinyl peptide in assembly. Biochemistry 14:1606- 11. With M. Berger. Purification of the subunits of transcarboxylase by affinity chromatography on avidin-sepharose. J. Biol. Chem. 250:927- 33. With M. Chuang, F. Ahmad, and B. Jacobson. Evidence that the two

420 B I O G RA P H I C A L EMOIRS partial reactions of transcarboxylation are catalyzed by two dis- similar subunits of tran scarboxylase . Biochemistry 14: 1611 -19. With Y. Milner and G. Michaels. Pyruvate, orthophosphate dikinase of Bacteroides OSUS and Propionibacterium shermanii. Methods Enzymol. 42:199-212. With W. E. O'Brien and S. Bowien. Isolation and characterization of a pyrophosphate-dependent phosphofructokinase from Propioni- bacterium shermanii. I. Biol. Chem. 250:8690-95. With M. Schulman. Enzymatic determination of microquantities of acetate. Methods Enzymol. 35:298-301. With M. Schulman. Succinyl-CoA: propionate CoA transferase from Propionibacterium shermanii. Methods Enzymol. 35:235-42. 1976 The reactive group of biotin in catalysis by biotin enzymes. Trends Biochem. Sci. 1:4-6. Subunit-subunit interactions of transcarboxylase. Fed. Proc. 35:1899- 1907. Reflections on Lynen's laboratory in Die Aktivierte Essigsaure and ihre Folgen. Autobiographische Beitrage non Schulem and Freunded Feodor Lynens, ed. G. Hartmann. Berlin: Walter de Gruyter. International responsibilities. Trends Biochem. Sci. 1:49-50. Trailing the propionic acid bacteria. In Reflections on Biochemistry: A Symposia in Honor of Severo Ochoa, ed. A. Kornberg, B. L. Horecker, L. Cornudella, and T. Oro. New York: Pergamon Press. With M. Berger. Immunochemistry of the subunits of transcarboxylase. 7. Biol. Chem. 251 :7021 -33. With Y. Milner. Steady state exchange kinetics. 7. Biol. Chem. 251:7920- 28. With A. M. Spronk and H. Yoshida. Isolation of 3-phosphohistidine from phosphoryl pyruvate, phosphate dikinase. Proc. Natl. A cad. Sci. U.S.A. 73:4415-19. With G. K. Zwolinski. Transcarboxylase: role of biotin, metals, and subunits in the reaction and its quaternary structure. Crit. Rev. Biochem. 4:47-122. 1977 Some reactions in which inorganic pyrophosphate replaces ATE and serves as a source of energy. Fed. Proc. 36:2197-2206.

HARLAN D G O FF WO O D 421 With R. E. garden. Biotin enzymes. Ann. Rev. Biochem. 46:385-413. With T. Chiao and E. M. Poto. A new large form of transcarboxylase with six peripheral subunits and twelve biotinyl carboxyl carrier subunits. 7. Biol. Chem. 252:1490-99. With E. M. Poto. The association-dissociation of transcarboxylase. Biochemistry 16: 1949-55. With W. E. O'Brien and G. Michaels. Properties of carboxy- transphosphorylase; pyruvate, phosphate dikinase; PPi-phospho- fructokinase and PPi-acetate kinase and their roles in the me- tabolism of inorganic pyrophosphate. Adv. Enzymol. 45:85-155. With N. H. Wrigley and T. Chiao. Electron microscopy of the large form of transcarboxylase with six peripheral subunits. 7. Biol. Chem. 252:1500-04. With G. K. Zwolinski, B. Bowien, and F. Harmon. The structure of the subunits of transcarboxylase and their relationship to the quaternary structure of transcarboxylase. Biochemistry 16:4627-37. 1978 With G. A. Cook, W. E. O'Brien, M. T. King, and R. Veech. A rapid, enzymatic assay for the measurement of inorganic pyrophosphate in animal tissue. Anal. Biochem. 91:557-65. With G. Michaels, Y. Milner, and B. R. Moskovitz. Pyruvate phos- phate dikinase. Metal requirements and inactivation of the en- zyme by sulfhydryl agents. J. Biol. Chem. 253:7656-61. With Y. Milner and G. Michaels. Pyruvate, phosphate dikinase of Bacteroides symbiosus. Catalysis of partial reactions and formation of phosphoryl and pyrophosphoryl forms of the enzyme. 7. Biol. Chem. 253:878-83. With B. R. Moskovitz. Requirement of monovalent cations for enolization of pyruvate by pyruvate, phosphate dikinase. J. Biol. Chem. 253:884- 88. With E. M. Poto, R. E. garden, and E. P. Lau. Photoaffinity labeling and stoichiometry of the coenzyme A ester sites of transcarboxylase. 7. Biol. Chem. 253:2979-83. With F. K. Welty. Purification of the "corrinoid" enzyme involved in the synthesis of acetate by Clostridium thermoaceticum. ]. Biol. Chem. 253:5832-38. With H. Yoshida. Crystalline pyruvate, phosphate dikinase from Bacteroides

422 B I O G RA P H I C A L EMOIRS symbioses. Modification of essential histidyl residues and bromopyruvate inactivation. 7. Biol. Chem. 253:7650-55. 1979 Obituary Feodor (Fitzi) Lynen. Trends Biochem. Sci. 4:300-2. The anatomy of transcarboxylase and the role of its subunits. Crit. Rev. Biochem. 7:143-60. The role of corrinoids in the total synthesis of acetate from CO2. In Vitamin B72, ed. B. Zagalak and W. Friedrich. Berlin: Walter de Gruyter. With H. L. Drake and N. H. Goss. A new, convenient method for the rapid analysis of inorganic pyrophosphate. Anal. Biochem. 94:117- 20. With W. L. Maloy, B. U. Bowien, G. K. Zwolinski, K. G. Kumar, L. H. Ericsson, and K. A. Walsh. Amino acid sequence of the biotinyl subunit from transcarboxylase. 7. Biol. Chem. 254:11615-22. With L. T. Waber. Mechanism of acetate synthesis from CO2 by Clostridium acidiurici. ]. Bacteriol. 140:468-78. 1980 IUB and the person. Trends Biochem. Sci. 4:I-II. With H. L. Drake and S. Hu. Purification of carbon monoxide dehy- drogenase, a nickel enzyme from Clostridium thermoaceticum. ]. Biol. Chem. 255:7174-80. With C. T. Evans and N. H. Goss. Pyruvate, phosphate dikinase: affinity labeling of the adenosine 5'-triphosphate-adenosine 5'- monophosphate site. Biochemistry 19:5809-14. With N. H. Goss and C. T. Evans. Pyruvate, phosphate dikinase: sequence of the histidyl peptide, the pyrophosphoryl and phos- phoryl carrier. Biochemistry 19:5805-9. With F. R. Harmon, M. Berger, H. Beegen, and N. Wrigley. Transcarboxylase: an electron microscopic study of the enzyme with antibodies to biotin. 7. Biol. Chem. 255:9458-64. With F. R. Harmon, B. Wuhr, K. Hubner, and F. Lynen. Compari- son of the biotination of apotranscarboxylase and its aposubunits. Is assembly essential for biotination? J. Biol. Chem. 255:7397-7409. 1981 Obituary, Merton F. Utter. Trends Biochem. Sci. 6:V-VI.

HARLAN D G O FF WO O D 423 Metabolic cycles in the fermentation of propionic acid bacteria. In Current Topics in Cellular Regulation, vol. 18, ed. R. Estabrook and P. Srere. New York: Academic Press. With C. Bahler, N. Goss, and E. Poto. Transcarboxylase: dissocia- tion and reassociation of the central hexameric subunit. Biochem. Intl. 3:349-58. With H. L. Drake and S. Hu. Purification of five components from Clostridium thermoaceticum which catalyzes synthesis of acetate from pyruvate and methyltetrahydrofolate. Properties of phospho- transacetylase. 7. Biol. Chem. 256:11137-44. 1982 From CO2 to acetate. In From Cyclotrons to Cytochromes: Essays in Mo- lecular Biology and Chemistry, ed. N. O. Kaplan and A. Robinson. New York: Academic Press. The discovery of the fixation of CO2 by heterotrophic organisms and metabolism of the propionic acid bacteria. In Of Oxygen, Fuels, and Living Matter; Part 2, ed. G. Semenza. New York: Tohn Wiley & Sons. With H. L. Drake and S. Hu. Studies with Clostridium thermoaceticum and the resolution of the pathway used by acetogenic bacteria that grow on carbon monoxide or carbon dioxide and hydrogen. In Proceedings Biochemistry Symposium, ed. E. S. Snell. Annual Re- v~ews. With N. H. Goss. Covalent chemistry of pyruvate, orthophosphate dikinase. Methods Enzymol. 87:51-66. With F. R. Harmon and N. H. Goss. Stabilization of the quaternary structure of transcarboxylase by cobalt(II) ions. Biochemistry 21:2847- 52. With T. P. Hennessey, W. C. Tohnson, and C. Bahler. Subunit inter- actions of transcarboxylase as studied by circular dichroism. Bio- chemistry 21:642-46. With S. Hu and H. L. Drake. Synthesis of acetyl coenzyme A from carbon monoxide, methyltetrahydrofolate, and coenzyme A by enzymes from Clostridium thermoaceticum. J. Bacteriol. 149 :440-48. With G. K. Kumar. Intrinsic fluorescence of transcarboxylase dur- ing subunit-subunit interactions. Biochem. Intl. 4:605-16. With G. K. Kumar, C. R. Bahler, and R. B. Merrifield. The amino

424 B I O G RA P H I C A L EMOIRS acid sequences of the biotinyl subunit essential for the associa- tion of transcarboxylase. 7. Biol. Chem. 257:13828-34. With L. G. Ljungdahl. Acetate Biosynthesis Vitamin B72, vol. 2, ed. D. Dolphin. New York: John Wiley & Sons. With W. T. Whelan. Freedom to meet. Trends Biochem. Sci. 7:351. 1983 With B. R. Landau. The pentose cycle in animal tissues: evidence for the classical and against the 'L-type' pathway. Trends Biochem. Sci. 8:292-96. With N. F. Phillips and N. H. Goss. Modification of pyruvate, phos- phate dikinase with pyridoxal 5'-phosphate: evidence for a cata- lytically critical lysine residue. Biochemistry 22:2518-23. 1984 With N. H. Goss. Formation of N-(biotinyl~lysine in biotin enzymes. Methods Enzymol. 107:261-78. With S. Hu and E. Pezacka. Acetate synthesis from carbon monox- ide by Clostridium thermoaceticum. Purification of the corrinoid protein. 7. Biol. Chem. 259:8892-97. With E. Pezacka. Role of carbon monoxide dehydrogenase in the autotrophic pathway used by acetogenic bacteria. Proc. Natl. A cad. Sci. U. S.A. 81:6261 -65. With E. Pezacka. The synthesis of ace tyl-CoA by Clostridium thermoaceticum from carbon dioxide, hydrogen, coenzyme A and methyltetra- hydrofolate. Arch. Microbiol. 137: 63-69. With N. A. Robinson and N. H. Goss. Polyphosphate kinase from Propionibacterium shermanii: formation of an enzymatically active insoluble complex with basic proteins and characterization of synthesized polyphosphate. Biochem. Intl. 8:757-69. 1985 The role of the International Union of Biochemistry (IUB). BioEssays 3:42-44. Then and now. Ann. Rev. Biochem. 54:1-41. Inorganic pyrophosphate and polyphosphates as sources of energy. Curr. Top. Cell. Regul. 26:355-69. With D. V. Craft, N. H. Goss, and N. Chandramouli. Purification of

HARLAN D G O FF WO O D 425 biotinidase from human plasma and its activity on biotinyl pep- tides. Biochemistry 24:2471-76. With N. H. Goss. Phosphorylation enzyme of the propionic acid bacteria and the roles of ATE, inorganic pyrophosphate, and polyphosphates. Proc. Natl. Acad. Sci. U.S.A. 82:312-15. With G. K. Kumar. Transcarboxylase: its quaternary structure and the role of the biotinyl subunit in the assembly of the enzyme and in catalysis. Ann. N.Y. A cad. Sci. 447:1-22. With G. K. Kumar and H. Beegen. Assembly of subunits and struc- ture of transcarboxylase: sequence requirement and electron mi- croscopy of crystals. Ann. N.Y. A cad. Sci. 447:403-5. With S. W. Ragsdale. Acetate biosynthesis by acetogenic bacteria. Evidence that carbon monoxide dehydrogenase is the condens- ing enzyme that catalyzes the final steps of the synthesis. 7. Biol. Chem. 260:3970-77. With S. W. Ragsdale and W. E. Antholine. Evidence that an iron- nickel-carbon complex is formed by reaction of CO with the CO dehydrogenase from Clostridium thermoaceticum. Proc. Natl. A cad. Sci. U.S.A. 82:6811-14. 1986 The synthesis of lactose and related investigations. Vlaams Diergeneeskd. Tijdschr. 55 :274-85. With T. E. Clark and H. Beegen. Isolation of intact chains of polyphosphate from Propionibacterium shermanii grown on glucose or lactate. 7. Bacteriol. 168:1212-19. With C. Pepin. Polyphosphate glucokinase from Propionibacterium shermanii. Kinetics and demonstration that the mechanism in volves both processive and nonprocessive type reactions. 7. Biol. Chem. 261:4476-80. With C. A. Pepin and N. A. Robinson. Determination of the size of polyphosphates with polyphosphate glucokinase. Biochem. Intl. 12:111- 23. With E. Pezacka. The autotrophic pathway of acetogenic bacteria. Role of CO dehydrogenase disulf~de reductase. J. Biol. Chem. 261:1609- 15. With N. F. B. Phillips. Isolation of pyrophosphohistidine from pyrophosphorylated pyruvate, phosphate dikinase. Biochemist7y 25:1644- 49.

426 B I O G RA P H I C A L EMOIRS With S. W. Ragsdale and E. Pezacka. The acetyl-CoA pathway: a newly discovered pathway of autotrophic growth. Trends Biochem. Sci. 11:14-18. With S. W. Ragsdale and E. Pezacka. A new pathway of autotrophic growth utilizing carbon monoxide or carbon dioxide and hydro- gen. Biochem. Intl. 12:421-40. With S. W. Ragsdale and E. Pezacka. The ace tyl-CoA pathway of autotrophic growth. FEMS Microbiol. Rev. 39: 345-62. With N. A. Robinson. Polyphosphate kinase from Propionibacterium shermanii. Demonstration that the synthesis and utilization of polyphosphate is by a processive mechanism. 7. Biol. Chem. 261:4481- 85. With E. Skrzpczak-Tankum, A. Tulinsky, T. P. Fillers, and K. G. Kumar. Preliminary crystallographic data and quaternary structural im- plications of the central subunit of the multi-subunit complex transcarboxylase. 7. Mol. Biol. 188 :495-98. 1987 With T. E. Clark. Preparation of standards and determination of sizes of long-chain polyphosphates by gel electrophoresis. Anal. Biochem. 161 :280-90. With C. A. Pepin. The mechanism of utilization of polyphosphate by polyphosphate glucokinase from Propionibacterium shermanii. I. Biol. Chem. 262:5223-26. With N. A. Robinson and T. E. Clark. Polyphosphate kinase from Propionibacterium shermanii. Demonstration that polyphosphates are primers and determination of the size of the synthesized polyphosphate. J. Biol. Chem. 262:5216-22. With N. A. Robinson, C. Pepin, and T. E. Clark. Polyphosphate ki- nase and polyphosphate glucokinase of Propionibacterium shermanii. In Phosphate Metabolism and Cellular Regulation in Microorganisms, ed. A. Torriani-Gorini and F. C. Rothman. Washington, D.C.: American Society for Microbiology. 1988 Squiggle phosphate of inorganic pyrophosphate and polyphosphates. In The Roots of Modern Biochemistry, ed. H. Kleinkauf, H. von Dohren, and L. Tacnicke. Berlin: Walter de Gruyter.

HARLAN D G O FF WO O D 427 With J. E. Clark. Biological aspects of inorganic polyphosphates. Ann. Rev. Biochem. 57:235-60. With G. K. Kumar and H. Beegen. Involvement of tryptophans at the catalytic and subunit-binding domains of transcarboxylase. Biochemistry 27:5972-78. With G. K. Kumar, F. C. Haase, and N. F. Phillips. Involvement and identification of a tryptophanyl residue at the pyruvate binding site of transcarboxylase. Biochemistry 27:5978-83. With E. Pezacka. Acetyl-CoA pathway of autotrophic growth. Identi- fication of the methyl-binding site of the CO dehydrogenase. 7. Biol. Chem. 263:16000-06. With S. W. Ragsdale, T. A. Morton, L. G. Ljungdahl, and D. V. DerVartanian. Nickel in CO dehydrogenase. In The Bioinorganic Chemistry of Nickel, ed. T. R. Lancaster, Tr. New York: VCH Publish ers. With D. Samols, C. G. Thornton, V. L. Murtif, G. K. Kumar, and F. C. Haase. Evolutionary conservation among biotin enzymes. 7. Biol. Chem. 263:6461-64. With T. Shanmugasundaram and G. K. Kumar. Involvement of tryp- tophan residues at the coenzyme A binding site of carbon mon- oxide dehydrogenase from Clostridium thermoaceticum. Biochemistry 27:6499-6503. With T. Shanmugasundaram and S. W. Ragsdale. Role of carbon monoxide dehydrogenase in acetate synthesis by the acetogenic bacterium, Acetobacterium woodii. BioFactors 1:147-52. With B. Shenoy. Purification and properties of the synthetase cata- lyzing the biotination of the aposubunit of transcarboxylase from Propionibacterium shermanii. FASEB ]. 2:2396-2401. 1989 Past and present of CO2 utilization. In Autotrophic Bacteria, ed. H. G. Schlegel and B. Bowien. New York: Springer-Verlag. With T. Shanmugasundaram, G. K. Kumar, and B. C. Shenoy. Chemical modification of the functional arginine residues of carbon mon- oxide dehydrogenase from Clostridium thermoaceticum. Biochemistry 28:7112-16.

428 B I O G RA P H I C A L 1991 EMOIRS Life with CO or CO2 and H2 as a source of carbon and energy. FASEBJ. 5:156-63. With L. G. Ljungdahl. Autotrophic character of the acetogenic bac- teria. In Variations in Autotrophic Life, ed. J. M. Shively and L. L. Barton. New York: Academic Press. With T. A. Morton, J. A. Runquist, S. W. Ragsdale, T. Shanmugasundaram, and L. G. Ljungdahl. The primary struc- ture of the subunits of carbon monoxide dehydrogenase/acetyl- CoA synthase from Clostridium thermoaceticum. /. Biol. Chem. 266:2382 28. With T. Shanmugasundaram. Interaction of ferredoxin with carbon monoxide dehydrogenase from Clostridium thermoaceticum. /. Biol. Chem. 267:897-900. 1992 With B. C. Shenoy, Y. Xie, V. L. Park, G. K. Kumar, H. Beegen, and D. Samols. The importance of methionine residues for the ca- talysis of the biotin enzyme, transcarboxylase. Analysis by site- directed mutagenesis. 7. Biol. Chem. 267:18407-12. 1993 With S. B. Woo, B. C. Shenoy, W. J. Magner, G. K. Kumar, H. Beegen and D. Samols. Effect of deletion from the carboxyl ter- minus of the 12S subunit of activity of transcarboxylase. 7. Biol. Chem. 268:16413-19. With C. G. Thornton, G. K. Kumar, F. C. Haase, N. F. B. Phillips, S. B. Woo, V. M. Park, W. J. Magner, S. B. Shenoy and D. Samols. Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli. /. Bacteriol. 175:5301-8. With C. G. Thornton, G. K. Kumar, B. C. Shenoy, F. C. Haase, N. F. B. Phillips, V. M. Park, W. J. Magner, D. P. Hejlik and D. Samols. Primary structure of the 5S subunit of transcarboxylase as de- duced from the genomic DNA sequence. FEBS Lett. 330:191-96. With N. F. B. Phillips and P. J. Horn. The polyphosphate and ATP- dependent glucokinase from Propionibacterium shermanii: both ac- tivities are catalyzed by the same protein. Arch. Biochem. Biophys. 300:309-19.