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Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

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Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
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Antigen Processing Pathways01:31

Antigen Processing Pathways

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MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
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Vitamins01:30

Vitamins

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Vitamins, derived from the Latin word for life, are essential organic substances required in small quantities for optimal growth and overall well-being. Unlike other organic nutrients, vitamins don't act as sources of energy or building materials but rather facilitate these nutrients' utilization by the body. Vitamins are predominantly coenzymes, assisting enzymes in specific chemical actions, like the oxidation of glucose for energy involving B vitamins. Most vitamins are not produced...
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Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
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Protein Transport to the Inner Chloroplast Membrane01:18

Protein Transport to the Inner Chloroplast Membrane

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Proteins targeted to the inner chloroplast membrane, or plastid proteins, are transported by two general pathways: the stop-transfer and the re-insertion or post-import pathways. Most plastid proteins carry N-terminal transit sequences and internal import sequences targeting it to the specific chloroplast subcompartment. Proteins targeted by the stop-transfer pathway have internal hydrophobic sequences that inhibit their translocation into the stroma. As a result, these precursors are arrested...
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Related Experiment Video

Updated: Sep 29, 2025

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
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Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin

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Intracellular processing of vitamin B12 by MMACHC (CblC).

Luciana Hannibal1, Donald W Jacobsen2

  • 1Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.

Vitamins and Hormones
|March 26, 2022
PubMed
Summary

Vitamin B12 (cobalamin) is essential but must be processed by the MMACHC protein (CblC) for cellular use. CblC defects cause cblC disease, preventing B12 activation and leading to metabolic disorders.

Keywords:
CblCCobalaminCobalamin deficiencyCobalamin processingHomocysteineInborn errors of metabolismMMACHCMethylmalonic aciduriaVitamin B(12)cblC disease

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Author Spotlight: Investigating Physiological Functions of Vitamin A Transporters Using HPLC-Based Vitamin A Profiling
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Area of Science:

  • Biochemistry
  • Genetics
  • Metabolic Disorders

Background:

  • Vitamin B12 (cobalamin) is a vital micronutrient synthesized by microorganisms and obtained through diet or supplements.
  • Dietary B12 exists in forms like HOCbl, MeCbl, and AdoCbl, while CNCbl is common in supplements.
  • These forms require intracellular processing by the MMACHC protein (CblC) to become biologically active.

Purpose of the Study:

  • To review the structural and functional aspects of intracellular vitamin B12 processing by CblC.
  • To explore CblC's partners and potential regulators in B12 metabolism.
  • To understand the molecular basis of cblC disease, an inborn error of B12 metabolism.

Main Methods:

  • Review of current scientific literature on vitamin B12 metabolism and CblC function.
  • Analysis of genetic mutations affecting MMACHC and their impact on CblC activity.
  • Examination of the biochemical pathways involving B12-dependent enzymes (MS and MUT).

Main Results:

  • CblC processes dietary B12 forms into cob(II)alamin, a precursor for B12-dependent enzymes.
  • Defects in MMACHC (CblC) impair cob(II)alamin formation, leading to cblC disease.
  • CblC dysfunction results in elevated homocysteine and methylmalonic acid due to inactive MS and MUT enzymes.

Conclusions:

  • Intracellular B12 processing by CblC is critical for activating essential metabolic enzymes.
  • Mutations in MMACHC cause cblC disease, characterized by severe metabolic abnormalities.
  • Understanding CblC's function is key to addressing B12 metabolism disorders and related genetic conditions.