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In the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination has been effective in preventing COVID-19 infections and related mortality. The SARS-CoV-2 vaccination was also recommended by the international society for patients with inflammatory bowel disease (IBD). However, IBD patients were not recruited in prospective randomized clinical vaccine studies. To evaluate the efficacy and safety of SARS-CoV-2 vaccination in IBD patients, we conducted this systemic review and meta-analysis.We systematically searched PubMed, Medline, and the Cochrane Library for studies published between January 1, 2019, and September 9, 2021. Studies written in English reported the efficacy, seroconversion (anti-SARS-CoV-2 anti-spike (S) antibody titer beyond the threshold) rate, and adverse events after the SARS-CoV-2 vaccination in IBD patients. We extracted the author, date, study design, country, types of SARS-CoV-2 vaccination, number of IBD patients receiving SARS-CoV-2 vaccinations, and study outcomes. Published data from the enrolled studies were pooled to determine effect estimates. The study protocol was registered in PROSPERO (CRD42021264993).We analyzed findings from 27 454 IBD patients who received SARS-CoV-2 vaccinations in 11 studies that met the inclusion criteria. The post-SARS-CoV-2 vaccination COVID-19 infection rate was comparable between the IBD patients and non-IBD patients (odds ratio [OR], 1.28 [95% CI, 0.96-1.71]) and higher in nonvaccinated IBD patients compared with vaccinated IBD patients (OR, 8.63 [95% CI, 5.44-13.37]). The adverse event rate, severe adverse events, and mortality after the SARS-CoV-2 vaccination were 69%, 3%, and 0%, respectively.The SARS-CoV-2 vaccine is effective and tolerated in preventing COVID-19 infections in IBD patients. Over 98% of patients had seroconversion after receiving all doses of the SARS-CoV-2 vaccination, and the influence of biologics on vaccination was limited. The SARS-CoV-2 vaccination is recommended for IBD patients.

BACKGROUND With the growth of the aging population, the need for colonoscopies in nonagenarians is rising. However, few data on colonoscopies in extremely elderly individuals are available. To better acknowledge the role of colonoscopies in this specific group of patients, we conducted this study to evaluate the safety and clinical impact of colonoscopy in nonagenarian patients. METHODS We performed a retrospective cohort study comparing nonagenarians who received colonoscopy in a tertiary medical center in Taiwan in 2016 with 76-80-year-old patients (relatively elderly patients) who were 1:1 propensity score matched by sex as the control subjects. The postcolonoscopy 30-day adverse events, mortality and long-term survival were recorded. RESULTS A total of 137 nonagenarians and 137 relatively elderly patients were included. The nonagenarians receiving colonoscopy were more likely to be hospitalized (40.1% vs. 19.7%, p < 0.001), and the adjusted colonoscopy completion rates were comparable in both groups (92.0% vs. 97.1%, p = 0.063). The overall adverse event rate and postcolonoscopy 30-day mortality rates were low in both groups (2.9% vs. 1.5%, p = 0.409 and 2.2% vs. 1.5%, p = 0.652, respectively). A total of 18.2% of the nonagenarians were diagnosed with advanced neoplasia. Among the nonagenarians diagnosed with colorectal cancer, the patients receiving surgery had a significantly lower risk of death than the patients receiving conservative management (hazards ratio 0.1044, 0.01275-0.8529, p = 0.0352). CONCLUSION Colonoscopy in patients older than 90 years is generally safe. Colonoscopy findings that led to surgery in nonagenarians diagnosed with colorectal cancer were associated with survival benefits.

Background Hyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATP-binding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin; however, little is known about these transporters and the risk of DILI. The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia. Methods A total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays. Results There were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs 27.9%, p = 0.048). Conclusion Carriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.

Background Nonalcoholic steatohepatitis (NASH) is closely related to reactive oxygen species (ROS). Superoxide anion radicals, the main product of ROS, can be reduced by manganese superoxide dismutase (SOD2) to hydrogen peroxide, which is further reduced by catalase (CAT) and glutathione peroxidase (GPX) to water. We aimed to investigate the association between the most important genetic variants of SOD2, CAT, and GPX1 and susceptibility to NASH. Methods A total of 126 adults with liver tissue-verified NASH, 56 patients with liver tissue-verified nonalcoholic fatty liver (NAFL), and 153 healthy controls were enrolled. Their DNA profiles were retrieved for genotype assessment of SOD2 47T>C (rs4880), CAT -262C>T (rs1001179), and GPX1 593C>T (rs1050450) variation. Results There were statistical differences between the SOD2 and CAT genotypes across the NASH, NAFL, and control groups, but not GPX1. The NASH group had a significantly higher frequency of subjects with SOD2 C allele (38.8%) compared with the NASL group (25.0%) and the controls (22.9%, p = 0.010). Similarly, the NASH group had a significantly higher percentage of subjects with CAT T allele (23.0%) compared with the NAFL group (10.7%) and the controls (7.2%, p = 0.001). For subjects with both the SOD2 C allele and CAT T allele, 88.2% were in the NASH group. After adjusting for confounders, the CAT mutant T allele and SOD2 mutant C allele were still the highest independent risk factors for NASH (odds ratio [OR] 3.10 and 2.36, respectively). In addition, there was a synergistic effect for those two alleles and the occurrence of NASH with an adjusted OR of 8.57 (p = 0.030). Conclusion The genetic variations of CAT and SOD2 may increase the risk of NASH, which may aid in the screening of patients who are at high risk of NASH, and offer a potential anti-oxidant targeting route for the treatment of NASH.

Hepatitis delta virus (HDV) is a defective virus that relies on the supply of hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV) to assemble HDV virions and infect hepatocytes. However, controversy remains in whether the presence of HDV increases the risk of hepatocellular carcinoma (HCC). Our aim is to evaluate the influence of HDV on the risk of HCC through a systematic review and meta-analysis.A review of all English-language literature was conducted in the major medical databases using the subject search terms "hepatocellular carcinoma," "liver cancer," "hepatic tumor," and "hepatitis delta." A meta-analysis of the qualifying publications was then performed.The meta-analysis included 21 studies, which revealed a significantly higher risk of HCC among patients with HDV/HBV dual infection (odds ratio [OR] = 2.08, 95% confidence interval [CI], 1.37-3.14, p 0.01) compared with those with HBV monoinfection. Those with HDV/HBV dual infection remained at higher risk of HCC in the subgroup analysis, irrespective of the status of hepatitis C virus (HCV) or human immunodeficiency virus (HIV) coinfection and in different ethnicities. The HCC risk remained higher in patients with HDV/HBV dual infection with heterogeneous fibrosis stage (OR = 2.04, 95% CI, 1.31-3.17, p 0.01). The difference in the risk of HCC between HDV/HBV dual infection and HBV monoinfection was not statistically significant in patients with cirrhosis or advanced fibrosis (OR = 1.84, 95% CI, 0.48-7.02, p = 0.37). However, this subgroup comprised only two studies.HDV and HBV dual infection significantly increase the risk of HCC development compared with HBV monoinfection.

BACKGROUND The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens. METHODS We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis. RESULTS A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001). CONCLUSION The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.

OBJECTIVES Sulfamethoxazole-trimethoprim (SMX-TMP) is one of the most frequently used antibiotics. SMX is metabolized by N-acetyltransferase (NAT) and cytochrome P450 2C9 (CYP2C9) to nontoxic or toxic intermediates. Little is known about the association between genetic variations of these enzymes and SMX-TMP-induced liver injury (SILI). The aim of this study was to explore the genetic polymorphisms of NAT2 and CYP2C9 and the susceptibility to SILI in a Han Chinese population. METHODS A total of 158 patients with SILI and 145 controls were recruited in this study. PCR-based genotyping with matrix-assisted laser desorption ionization-time of flight was used to assay the major NAT2 and CYP2C9 genotypes including NAT2 rs1495741, rs1041983, rs1801280, CYP2C9 rs1799853, rs1057910 and rs4918758. RESULTS The SILI group had a higher frequency of the NAT2 rs1495741 variant AA genotype and rs1041983 variant TT genotype than the controls (42.4 vs. 25.5%; P = 0.008, and 40.5 vs. 25.5%; P = 0.022, respectively). The SILI group had more slow acetylators than the controls (43.7 vs. 25.5%; P = 0.001). There were no significant differences in the genetic variations of CYP2C9 between the SILI and control groups. After adjusting for confounding factors, the NAT2 slow acetylators still had an increased risk of SILI (adjusted OR: 2.49; 95% confidence interval: 1.46-4.24; P = 0.001), especially in those with hepatocellular and mixed type SILI. CONCLUSIONS NAT2 slow acetylators are associated with a higher risk of SILI in the Han Chinese population. However, CYP2C9 genetic polymorphisms are not associated with the susceptibility to SILI.

Background/purpose Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically. Methods Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT. Results The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients’ feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT. Conclusion Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.

BACKGROUND Worldwide, proton pump inhibitors (PPIs) are commonly used for the treatment of peptic ulcer and gastro-esophageal reflux disease. Recently, concern has arisen over the potential association between PPIs and hepatocellular carcinoma (HCC). The aim of the current study was to evaluate the influence of PPI use on the risk of HCC, through a systematic review and meta-analysis. METHODS A review of all English-language literature was conducted, using the subject search terms: "hepatocellular carcinoma", "liver cancer", "hepatic tumor", and "proton pump inhibitor" in the major medical databases. A meta-analysis of the qualifying publications was then performed. RESULTS A total of five studies, which had shown that PPIs were associated with HCC (crude risk ratio [RR] = 2.27, 95% confidence interval [CI]: 1.44-3.57; p < 0.01) when an unadjusted RR were adopted, were eligible for meta-analysis. It was observed that the cumulative dose of PPIs may increase the risk of HCC in a linear model (p < 0.01). However, when using data that were adjusted by comorbidities and concurrent medications, the association between PPIs and HCC became insignificant (adjusted RR = 1.62, 95% CI: 0.89-2.93; p = 0.11) and this result was consistent in the sensitivity analysis. CONCLUSION The current meta-analysis has shown that PPI use does not significantly increase the risk of HCC after adjusting for confounding factors. However, further studies are warranted to verify the association between PPIs and HCC in special populations, such as viral or alcoholic liver diseases.

BACKGROUND Antituberculosis (TB) drug-induced liver injury (ATLI) is a common adverse effect of anti-TB drugs. Whether regular monitoring of liver function can ameliorate ATLI has been widely debated. The current study aimed to investigate the liver test monitoring status of patients receiving anti-TB treatment in Taiwan, as well as the impact of scheduled liver function monitoring on the risk of ATLI. METHODS Patients who received anti-TB treatment at our hospital between 2009 and 2017 were enrolled for retrospective analysis. RESULTS A total of 1062 patients were included, and of them 469 (44.2%) received regular liver function monitoring (good monitoring group). ATLI was recognized in 100 (9.4%) patients. The good monitoring group detected more ATLI cases early compared with the poor monitoring group (14.7% vs 5.2%, and 21.4 vs 61.6 days, p < 0.01), with a lower peak serum alanine aminotransferase (276.1 vs 507.1 IU/L, p = 0.05). CONCLUSION In the current study, less than half of all patients who received anti-TB drugs had their liver function monitored regularly. Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury. The implementation of periodic liver function monitoring tests in patients receiving anti-TB treatment should be re-emphasized and encouraged.

BACKGROUND We aimed to investigate the long-term effects of metabolic profiles and microbiota status in patients after upper gastrointestinal (GI) surgery and lower GI surgery and compared them with a control group. METHODS In this cross-sectional study, we analyzed the occurrence of metabolic syndrome (MS) in 10 patients who underwent curative total gastrectomy with Roux-en-Y esophagojejunostomy (RYEJ) anastomosis, 11 patients who underwent curative partial colectomy with right hemicolectomy (RH), and 33 age- and sex-matched controls. Fecal samples were also analyzed by a next-generation sequencing method. RESULTS Compared with the control group, the occurrence of MS was significantly lower among patients who underwent total gastrectomy with RYEJ than the controls over the long-term follow-up (>8 years; p < 0.05). Patients who received RH only had a trend of higher serum fasting glucose (p = 0.10). The diversity of the gut microbiota significantly decreased after RH in comparison with the control group and RYEJ group, respectively (p < 0.05). Principal component analysis revealed significant differences between the control, RYEJ, and RH groups (p < 0.001). At the genus level, the ratio of Prevotella to Bacteroides (P/B) was significantly higher in the RYEJ group than in the control group, whereas the P/B ratio was significantly lower in the RH group than in the control group (p < 0.05). CONCLUSION Early gastric cancer patients who received total gastrectomy with RYEJ had a lower occurrence of MS than the controls, while early colorectal cancer patients who received RH were associated with a higher serum fasting glucose than the controls during long-term follow-up. In parallel with the metabolic differences, the P/B ratio was also significantly altered in patients after upper and lower GI surgery.

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease that associated with complicated interaction between immune, gut microbiota and environmental factors in a genetically vulnerable host. Dysbiosis is often seen in patients with IBD. Our aim is to investigate the fecal microbiota in patients with IBD and compared to healthy controls in Taiwan. Methods In this cross-sectional study, we investigated fecal microbiota in 20 patients with IBD and 48 healthy controls. Fecal samples from both IBD patients and controls were analyzed by next-generation sequencing method and relevant software. Results The IBD group showed lower bacterial richness and diversity compared to the control group. The principal coordinate analysis also revealed significant structural difference between the IBD group and the control group. These findings were consistent whether the analysis was based on operational taxonomic unit or amplicon sequence variant. However, no significant difference was found when comparing the composition of fecal microbiota between ulcerative colitis (UC) and Crohn’s disease (CD). Further analysis showed that Lactobacillus, Enterococcus, Bifidobacterium and Veillonella were dominant in the IBD group, while Faecalibacterium and Subdoligranulum were dominant in the control group at genus level. When comparing UC, CD and control group, Lactobacillus, Bifidobacterium and Enterococcus were identified as dominant genera in the UC group. Fusobacterium and Escherichia_Shigella were dominant in the CD group. Faecalibacterium and Subdoligranulum were dominant in the control group. Conclusions Compared to the healthy control, the IBD group showed dysbiosis with a significant decreased in both richness and diversity of gut microbiota.

BACKGROUND AND AIM The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all

Background Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. Methods We systemically reviewed all English-language literature in the major medical databases with the subject search terms “anti-tuberculosis drug-induced liver injury” and “anti-tuberculosis drug-induced hepatotoxicity”. We then performed a systematic review and meta-analysis of the papers relevant to hepatitis C in qualified publications. Results A total of 14 studies were eligible for analysis, which included 516 cases with ATDILI and 4301 controls without ATDILI. The pooled odds ratio (OR) of all studies for CHC infection to ATDILI was 3.21 (95% confidence interval (CI): 2.30–4.49). Subgroup analysis revealed that the CHC carriers had a higher risk of ATDILI than those without CHC both in Asians (OR = 2.96, 95% CI: 1.79–4.90) and Caucasians (OR = 4.07, 95% CI: 2.70–6.14), in those receiving standard four combination anti-TB therapy (OR = 2.94, 95% CI: 1.95–4.41) and isoniazid monotherapy (OR = 4.18, 95% CI: 2.36–7.40), in those with a strict definition of DILI (serum alanine aminotransferase [ALT] > 5 upper limit of normal value [ULN], OR = 2.59, 95% CI: 1.58–4.25) and a loose definition of DILI (ALT > 2 or 3 ULN, OR = 4.34, 95% CI: 2.96–6.37), and in prospective studies (OR = 4.16, 95% CI: 2.93–5.90) and case–control studies (OR = 2.43, 95% CI: 1.29–4.58). Conclusion This meta-analysis suggests that CHC infection may increase the risk of ATDILI. Regular liver tests are mandatory for CHC carriers under anti-TB therapy.

Chlorophyll biosynthesis starts with the synthesis of glutamyl-tRNA (glu-tRNA) by a glutamyl-tRNA synthetase (Glu RS). The glu-tRNA is subsequently transformed to delta-aminolevulinic acid (ALA), which is a committed and regulated precursor in the chlorophyll biosynthetic pathway. The Glu RS from a green alga, Chlamydomonas reinhardtii, was purified and shown to be able to synthesize glu-tRNA and to participate in ALA synthesis in a coupled enzyme assay. Physical and chemical characterization of the purified Glu RS indicated that the enzyme had been purified to homogeneity. The purified enzyme has a native molecular weight of 60,000, an isoelectric point of 4.6, and it formed a single band of 32,500 daltons when analyzed by a silver stained denaturing gel. The N-terminal amino acid sequence of the 32,500 dalton protein was determined to be Asn-Lys-Val-Ala-Leu-Leu-Gly-Ala-Ala-Gly. The molecular weight analyses together with the unambiguous N-terminal amino acid sequence obtained from the purified enzyme suggested that the native enzyme was composed of two identical subunits. Polyclonal antibodies raised against the purified and denatured enzyme were able to inhibit the activity of the native enzyme and to interact specifically with the 32,500 dalton band on Western blots. Thus, the antibodies provided an additional linkage for the structural and functional identities of the enzyme. In vitro experiments showed that over 90% of the glu RS activity was inhibited by 5 micromolar heme, which suggested that Glu RS may be a regulated enzyme in the chlorophyll biosynthetic pathway.

The biosynthesis of chlorophyll has been shown to be regulated by the availability of the first committed intermediate of the pathway, δ -aminolevulinic acid (ALA)(1). ALA destined for chlorophyll is synthesized from glutamate. Enzymes converting glutamate to ALA have been found in soluble fractions of barley (2), wheat (3), maize (4), Chiamy-domonas (5) and Chlorella (6). The enzymes from barley and Chlamydomonas have been separated by affinity columns into three fractions (5, 7). They are the Blue Sepharose bound (B), heme-Sepharose bound (H) and the runoff (R) fractions. Glutamate can be converted to glutamate-1-semial-dehyde (GSA) by H+B fractions using NADPH, ATP and Mg+2 as cofactors. The formation of ALA from GSA is catalysed by an aminotransferase in the R fraction. An RNA moiety present in the H fraction was found to be needed for the synthesis of ALA in Chlamydomonas (8). Similar results have been reported for Chlorella (9). In barley, the RNA fraction needed for ALA synthesis was isolated from plastids and purified by HPLC and gel electrophoresis (10). The purified RNA was found to hybridize to the plastid genome (10) and its nucleotide sequence was determined to be that of a tRNA (11).

The first committed intermediate of the chlorophyll biosynthetic pathway is δ-aminolevulinic acid (ALA). In plant cells, ALA is formed from glutamate by a pathway not yet clearly defined. One of the proposed pathways involves the reduction of glutamate to glutamate-1-semialdehyde (GSA) via a glutamyl-tRNA intermediate. GSA is then converted to ALA by an aminotransferase. We are studying this pathway using partially purified components from Chlamydomonas reinhardtii in in vitro reactions with [3H] l -glutamate as the substrate and analysis of the radioactive reaction products via HPLC. In reactions either lacking GSA-aminotransferase or containing gabaculine (an inhibitor of aminotransferase), a radioactive intermediate is formed which cochromatographs with synthetic GSA. As observed previously for ALA synthesis, the synthesis of this intermediate has an absolute requirement for RNA, ATP, and active enzymes, while the requirement for NADPH is less stringent. Both the accumulated intermediate and the synthetic GSA can be converted to ALA by the aminotransferase without any additional substrates or cofactors. These results support previous observations that GSA or a very similar compound is an intermediate of ALA synthesis.