Effect of vitamin B12 derivatives on urinary excretion of methylmalonic acid in liver diseases.

1. Twenty.one patients with liver diseases were studied for their urinary mehylmalonic acid excretion after a valine load by means of an improved thin layer chromatography. 2. Methylmalonic acid positive cases were found in four out of the ten patients with cirrhosis of the liver, all four with cirrhosis and diabetes mellitus, and none with acute hepatitis of icteric phase. No apparent correlation was found between the methylmalonic acid excretion and the extent of hepatic damage. 3. A large amount of methylmalonic acid found in the case (S. I.) with cirrhosis of the liver and diabetes mellitus after the valine load was not corrected by cyanocobalamin but by DBCC, suggesting an impaired transformation from cyanocobalamin to DBCC. However, the nature of the impairment remains unknown. ∗PMID: 4249892 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 24, 365-372 (1970) EFFECT OF VITAMIN B12 DERIVATIVES ON URINARY EXCRETION OF METHYLMALONIC ACID IN LIVER DISEASES Masatoshi U EDA and Kazuhisa T AKETA Departmen! of InJernal Me1icine, Okayama University Meiical School, Okayama, Japan (Direc/or: Prof K. Kosaka) Received for publication, February 20, 1970 Methylmalonic acid! is excreted in increased amount in the urine of patients with vitamin B12 deficiency 0, 2, 3, 4, 5). The coenzyme fo rm 2 of vitamin B12 is required for the conversion of methylm alonyl-CoA to succinyl-CoA, and the appearance of DECC in human and animal li vers has been also demonstrated (6). On the other hand, cyanocobalamin or hydroxocobalamin is converted into DBCC in rat and human livers (7), and dietary restriction of vitamin B. 2 results in a decrease of the hep atic coenzyme level (8). A possibility exists, therefore, that an impa ired conversion of vitamin B. 2 into DBCC might cause the lowering of the liver coenzyme content, hence the excretion of MMA. Recently, UKYO (9) reported patients with liver diseases who excreted MMA in urine after oral administration of valine which enhances M MA excretion in vitamin B.2 deficiency (5, 10). The present study wa s under. taken to know in what liver diseases MMA is excreted in urine and w hat effects vitamin B12 derivatives have on the MMA excretion. T he estimation of MMA in urine was carried out by a rapid thin layer chromatogra phic technique and its validity was also studied. SUBJECTS AND METHODS Twenty-four patients mostly of liver diseases (see Fig. 2) admitted to the Okayama University Hospital and its affiliated hospitals have been stu died. The patients have not received parenteral administration of vitamin B12 d erivatives and their oral administration, when they had been received, was di scontinued at least [or ten days before collection of urine for MMA assay. Urinary MMA was estimated semiquantitatively by thin layer chro matography essentially as described by BASHIR and others 3 (1) except for the develop1. MMA: methylmalonic acid 2. DBCC: 5, 6-dimeth) lbenzimidazol~lcobamidecoenz) me 3. In our preliminar" e: periments with their solvent s> stem, a diffi culty was found in separatipg MMA from hippuric acid, which is usually present in larg e c.uantities in urine. This difficulty could be eliminated by use of the s) stem of DREIF US and DUBE with minor modification;