Structural determinants for transport of lactase phlorizin-hydrolase in the early secretory pathway as a multi-domain membrane glycoprotein

Diekmann, Lena; Behrendt, Marc; Amiri, Mahdi; Naim, Hassan Y.

doi:10.1016/j.bbagen.2016.10.016

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…In fact, the association of this domain with other LPH domains that are transport-competent leads to their intracellular block in the ER. The unique N -glycosylation site in this domain is the site for its association with the lectin chaperone calnexin, thus facilitating the folding of the entire LPH molecule [25]. Domain III comprises the phlorizin hydrolase active site that possesses a wide specificity towards substrates like glycosyl- N -acylsphingosines and flavonoid glycosides [26].…”

Section: Structural and Biosynthetic Features Of Lphmentioning

confidence: 99%

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Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives

Wanes

Husein²,

Naim³

2019

Nutrients

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Congenital lactase deficiency (CLD) is a severe autosomal recessive genetic disorder that affects the functional capacity of the intestinal protein lactase-phlorizin hydrolase (LPH). This disorder is diagnosed already during the first few days of the newborn’s life due to the inability to digest lactose, the main carbohydrate in mammalian milk. The symptoms are similar to those in other carbohydrate malabsorption disorders, such as congenital sucrase-isomaltase deficiency, and include severe osmotic watery diarrhea. CLD is associated with mutations in the translated region of the LPH gene that elicit loss-of-function of LPH. The mutations occur in a homozygote or compound heterozygote pattern of inheritance and comprise missense mutations as well as mutations that lead to complete or partial truncations of crucial domains in LPH, such as those linked to the folding and transport-competence of LPH and to the catalytic domains. Nevertheless, the identification of the mutations in CLD is not paralleled by detailed genotype/protein phenotype analyses that would help unravel potential pathomechanisms underlying this severe disease. Here, we review the current knowledge of CLD mutations and discuss their potential impact on the structural and biosynthetic features of LPH. We also address the question of whether heterozygote carriers can be symptomatic for CLD and whether genetic testing is needed in view of the severity of the disease.

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Section: Structural and Biosynthetic Features Of Lphmentioning

confidence: 99%

“…( c ) In the Golgi apparatus, the pro-LPH is glycosylated and proteolytically cleaved to LPHßinitial. ( d ) LPHßinitial is sorted to the apical membrane (BBM) where pancreatic trypsin cleaves LPHßinitial to its final mature LPHßfinal form (see references [22,25,30,31,35]).…”

Section: Figurementioning

confidence: 99%

Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives

Wanes

Husein²,

Naim³

2019

Nutrients

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Digestion, absorption, metabolism, and physiological effects of lactose

Szilagyi

2019

Lactose

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Calcium-dependent complications of lactase deficiency in patients with type 2 diabetes mellitus

Андруша¹

2021

УТЖ

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Objective — to assess the degree of osteodeficiency and probability of osteoporotic fractures in patients with type 2 diabetes mellitus in the absence or presence of lactase deficiency. Materials and methods. All examined patients with type 2 diabetes mellitus were divided into 2 groups depending on the presence/absence of lactase deficiency. In addition to routine examination methods, specific methods were used for diagnosing lactase deficiency, assessing bone mineral density (using dual‑energy X‑ray absorptiometry) and bone quality (ultrasound densitometry), the state of bone remodelling (according to markers of bone resorption and formation), probability of osteoporotic fractures (using FRAX and QFracture calculators), dietary and lifestyle habits were also studied. Results. The changes have been revealed in both processes of bone remodelling — increased bone resorption and insufficient bone formation, and the activity of bone formation, which was the lowest in patients with lactase deficiency and type 2 diabetes mellitus. The results of X‑ray absorptiometry confirmed that osteoporosis was significantly more often in patients with type 2 diabetes mellitus in the presence of lactase deficiency. The use of ultrasonic densitometry confirmed the violation of bone tissue micro architectonics. The indicator of broadband ultrasound attenuation, which reflects the qualitative characteristics of bone tissue, was the lowest in patients with type 2 diabetes mellitus accompanied by lactase deficiency. The probability of osteoporotic fractures according to the results of the assessment with the online calculator FRAX® was higher than the average risk in both groups of patients. No significant difference was established in this indicator between these groups of patients in contrast to the risk calculated with the QFracture instrument — it was the highest in patients with lactase deficiency. Conclusions. The presence of lactase deficiency in patients with type 2 diabetes mellitus can be considered as a factor that contributes to the development of osteodeficiency, deterioration of the quality of bone tissue, imbalance in bone remodelling and an increase in the probability of osteoporotic fractures.

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Structural determinants for transport of lactase phlorizin-hydrolase in the early secretory pathway as a multi-domain membrane glycoprotein

Cited by 3 publications

References 25 publications

Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives

Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives

Digestion, absorption, metabolism, and physiological effects of lactose

Calcium-dependent complications of lactase deficiency in patients with type 2 diabetes mellitus

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