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Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives.

ABSTRACT: A case-control design determined whether konzo, an upper motoneuron disease linked to food (cassava) toxicity was associated with protein carbamoylation and genetic variations. Exon sequences of thiosulfate sulfurtransferase (TST) or mercaptopyruvate sulfurtransferase (MPST), plasma cyanide detoxification rates, and 2D-LC-MS/MS albumin carbamoylation were assessed in 40 children [21 konzo-affected and 19 putatively healthy controls, mean (SD) age: 9.2 (3.0) years] subjected to cognition and motor testing using the Kaufman Assessment Battery and the Bruininks/Oseretsky Test, respectively. Konzo was significantly associated with higher levels of carbamoylated peptides 206-219 (LDELRDEGKASSAK, pep1) after adjusting for age, gender, albumin concentrations and BUN [regression coefficient: 0.03 (95%CI:0.02-0.05), p = 0.01]. Levels of pep1 negatively correlated with performance scores at all modalities of motor proficiency (r = 0.38 to 0.61; all p < 0.01) or sequential processing (memory)(r = - 0.59, p = 0.00) and overall cognitive performance (r = - 0.48, p = 0.00) but positively with time needed for cyanide detoxification in plasma (r = 0.33, p = 0.04). Rare potentially damaging TST p.Arg206Cys (rs61742280) and MPST p.His317Tyr (rs1038542246) heterozygous variants were identified but with no impact on subject phenotypes. Protein carbamoylation appears to be a reliable marker for cassava related neurodegeneration.

SUBMITTER: Rwatambuga FA

PROVIDER: S-EPMC7855927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cassava (Manihot esculenta Crantz) is an essential stable food crop in Sub-Saharan Africa commonly consumed amongst the low-income communities in Africa. Though cassava roots and leaf have vast economic and commercial benefits, it produces cyanogenic glycosides, which are toxic and most often responsible for the bitter taste of some cassava cultivars. The study evaluates the cassava roots and leaves' cyanogenic potential and dry matter content of the Genetic Gain Assessment trial grown in a different environment. It establishes the association between the cyanogenic potential (CNP) and the roots and leaves dry matter (DM). Genetic Gain Assessment (GGA) cassava genotypes (N = 400) selected for the Uniform Yield Trial (UYT) breeding stage were planted under IVS (Dry season in Inland Valley Hydromorphic area) and Upland (rain-fed conditions) in two locations of IITA Research Farms, namely; Ibadan (IVS and Upland) and Mokwa (Upland) in Nigeria. The CNP content of cassava leaves in IVS, Mokwa, and Upland ranged from 3.39 to 272.16 mg/100 g, 4.28 to 228.72 mg/100 g, and 13.13 to 127.39 mg/100 g, respectively. However, the respective CNP range in root samples across IVS, Mokwa, and Upland was 0.76-76.31 mg/100 g, 0.94-136.53 mg/100 g, and 2.37-47.11 mg/100 g. Also, the mean ± SD of DM content of leaves were 27.97 ± 3.01%, 28.81 ± 4.01%, and 13.65 ± 3.69%, respectively, in IVS, Mokwa, and Upland, while the root samples had mean ± SD of DM content of 38.09 ± 4.80%, 32.69 ± ,5.93% and 24.63 ± 5.07% respectively. Furthermore, location and genotype had a highly significant effect (p < 0.001) on the CNP and DM of roots and leaves. Also, linear regressions were established between CNP and DM of root and leaf with regression equation; DM-Root = 1.1999*DM-Leaf (r = 0.956) and CNP-Root = 0.29006*CNP-Leaf (r = 0.54). The relationship between the DM (root and leaf) and CNP (root and leaf) could serve as a valuable "inter-prediction" tool for these parameters.

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Motor control and cognition deficits associated with protein carbamoylation in food (cassava) cyanogenic poisoning: Neurodegeneration and genomic perspectives.

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