CLPS Human
Description
Introduction to CLPS Human
CLPS Human, or Colipase Human Recombinant, is a protein co-enzyme essential for the optimal activity of pancreatic lipase during dietary fat digestion. Produced in Escherichia coli (E. coli), this recombinant protein is engineered to mimic the natural human colipase, which facilitates the hydrolysis of dietary triglycerides in the intestine by anchoring lipase to lipid micelles and counteracting bile salt inhibition .
Biochemical Properties and Formulation
CLPS Human is provided in a sterile solution optimized for stability and functionality:
| Parameter | Specification |
|---|---|
| Concentration | 0.25 mg/mL |
| Buffer | 20 mM Tris-HCl (pH 8.0) |
| Additives | 30% glycerol, 1 mM DTT, 0.1 M NaCl |
| Storage Recommendations | 4°C (short-term) or -20°C (long-term with 0.1% HSA/BSA) |
The inclusion of glycerol and DTT prevents aggregation and maintains structural integrity, while the absence of glycosylation simplifies reproducibility in experimental settings .
Functional Role in Lipid Metabolism
CLPS Human enables pancreatic lipase to bind effectively to lipid-water interfaces, even in the presence of bile salts. Its mechanism involves:
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Binding to Lipase: Stabilizes the hydrophobic binding site of lipase via interactions with its C-terminal domain.
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Micelle Anchoring: Facilitates non-covalent attachment of lipase to lipid micelles, enhancing enzymatic turnover .
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Activation Pathway: Secreted as inactive procolipase, which is activated by trypsin cleavage in the intestinal lumen .
Research Applications
CLPS Human is widely used in studies investigating:
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Lipid Digestion Dynamics: Models for malabsorption syndromes or enzyme replacement therapies.
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Protein-Protein Interactions: Structural analyses of colipase-lipase complexes.
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Bile Salt Inhibition: Mechanistic studies on bile salt interference in lipid metabolism.
Comparative Analysis with Homologous Proteins
While CLPS (colipase) is distinct from similarly named proteins like CLPP (mitochondrial protease) or CLP1 (tRNA splicing kinase), its role in lipid metabolism highlights unique functional specializations:
| Protein | Function | Associated Pathways |
|---|---|---|
| CLPS | Lipid digestion | Triglyceride hydrolysis |
| CLPP | Mitochondrial proteostasis | Protein degradation |
| CLP1 | tRNA processing | Neurological development |
Stability and Handling Protocols
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Short-Term Storage: Maintain at 4°C for 2–4 weeks.
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Long-Term Storage: Freeze at -20°C with carrier protein (e.g., 0.1% HSA/BSA) to prevent denaturation .
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Freeze-Thaw Cycles: Minimize to preserve activity.
Future Directions
Ongoing research aims to exploit CLPS Human in therapeutic contexts, such as designing lipase-colipase complexes for treating pancreatic insufficiency. Structural studies may further elucidate its role in metabolic disorders linked to lipid malabsorption.
Product Specs
Q&A
What is the CLPS and what were its primary research objectives?
The Collaborative Longitudinal Personality Disorders Study (CLPS) was developed to address critical gaps in understanding the nature, course, and impact of personality disorders (PDs). Unlike major Axis I disorders, there was little empirical knowledge regarding the short- or long-term course and outcome of PDs when the study was initiated. The primary objectives included examining the stability of personality disorders over time, assessing their public health impact through measures of functional impairment and treatment utilization, and evaluating the validity of categorical versus dimensional models of personality disorders .
How did CLPS define and measure "remission" in personality disorders?
In the CLPS methodology, "remission" was operationally defined as at least 12 consecutive months with no more than two criteria of the baseline disorder within the first 2 years of follow-up. This definition provided a standardized metric for measuring meaningful clinical improvement. The study found that more than half of PD patients showed remission according to this definition, challenging traditional assumptions about the immutability of personality disorders .
What assessment methods were employed in the CLPS for measuring psychosocial functioning?
The CLPS employed multiple validated assessment methods including the clinician-administered Longitudinal Interval Follow-up Evaluation (LIFE) and the self-report Social Adjustment Scale (SAS-SR). These complementary instruments assessed various domains of psychosocial functioning including work performance, social relationships, and leisure activities. This multi-modal approach allowed researchers to triangulate findings across different assessment methodologies .
How did the CLPS findings contribute to the reconceptualization of personality disorders?
The CLPS findings suggested that personality disorders might be more accurately reconceptualized as hybrids of stable personality traits and intermittently expressed symptomatic behaviors. While categorical diagnoses showed considerable instability over time, dimensional aspects of personality pathology demonstrated greater temporal consistency. These findings directly challenged the traditional conceptualization of PDs as purely categorical and wholly stable conditions, suggesting that PDs have both trait-like and state-like components .
What evidence did CLPS provide regarding dimensional versus categorical approaches to personality disorders?
The CLPS provided substantial empirical evidence that dimensional models of personality disorders demonstrated greater temporal stability than categorical diagnoses. While fewer than half of PD patients remained at full diagnostic criteria over intervals as short as 1-2 years, dimensional measures of PD criteria showed high correlations across assessments. These findings supported the notion that dimensional approaches might more accurately capture the nature of personality pathology, significantly influencing discussions about future diagnostic systems including DSM-V .
How did the CLPS methodology address potential artifacts in longitudinal assessment?
The CLPS researchers systematically examined whether observed changes in PD diagnoses might result from methodological artifacts. They investigated several potential confounds, including: (1) effects of concurrent major depressive disorder, (2) measurement differences between interview versus self-report methods, (3) influence of repeated interviews, and (4) rater unreliability or drift. The results indicated that none of these factors accounted for the degree of improvement observed, strengthening confidence in the validity of the findings about personality disorder course .
How did CLPS control for comorbid conditions in analyses of personality disorder impact?
The CLPS study employed statistical controls for demographic differences and comorbid Axis I psychopathology when comparing different personality disorder groups on measures of functional impairment. This methodological approach allowed researchers to isolate the specific impact of personality disorders separate from other psychiatric conditions. Even after these statistical controls, significant differences in functioning remained between PD groups, demonstrating the unique contribution of personality pathology to functional impairment .
What methodological approach did CLPS use to study the stability of functional impairment?
CLPS researchers conducted a prospective study of impairment in psychosocial functioning over the first 2 years of follow-up, examining seven distinct domains of functioning. This methodological approach allowed them to determine that improvement occurred in only three domains: social relationships with spouse/mate, recreation, and global social adjustment. Furthermore, these improvements were primarily observed in the Major Depressive Disorder (without PD) group rather than in personality disorder groups, highlighting the differential impact of Axis I versus Axis II pathology on functional recovery trajectories .
How did CLPS researchers address the ethical requirements for conducting longitudinal human research?
While the search results don't explicitly detail the ethical framework, the CLPS as a major human research initiative would have required comprehensive ethical protocols. The study maintained an ethical commitment to participants through its code of ethics which emphasized "the highest standards of ethics and business conduct" and compliance with "all laws, rules and regulations applicable to it or the conduct of its business" . For researchers planning similar studies, implementing analogous ethical frameworks is essential.
What is the relationship between personality traits and symptomatic behaviors in personality disorders according to CLPS?
CLPS findings suggest that dimensional personality traits appear to be the foundation of behaviors described by many PD criteria. The study found that traits are more enduring, possibly because they are more innate and proximal to genetic and biological mechanisms. In contrast, symptomatic behaviors emerged as more intermittent in expression, more influenced by development and learning, and more closely linked to life situations and stress. This distinction has important implications for treatment targeting and outcome measurement .
What were the key public health implications identified by the CLPS?
The CLPS confirmed that personality psychopathology constitutes a significant public health problem across multiple domains including: (1) associated functional impairment, (2) extensive treatment utilization, (3) negative prognostic impact on major depressive disorder, and (4) increased suicide risk. These findings established that PDs represent more serious forms of psychopathology by many impact indicators than Major Depressive Disorder without PD, challenging earlier clinical assumptions and providing empirical support for increased attention to personality pathology in public health initiatives .
How might the CLPS methodology inform data validation in other longitudinal datasets?
The methodology employed in CLPS demonstrates the importance of rigorous data validation procedures. As noted in other longitudinal datasets, such as the All of Us Research Program, ensuring data accuracy may require deprecating impacted tables when validation issues are identified, while still making deprecated data available to researchers until updated versions are released. This approach balances data integrity with continued research access, a model applicable to other longitudinal human studies .
What does CLPS suggest about the timeframe needed for meaningful personality disorder research?
The CLPS researchers noted that "the inherent stability of the traits underscores the need for data collected over considerable time periods, as noteworthy changes are more likely to be manifest over the course of a decade than over the course of a few years." This methodological insight suggests that future personality disorder research should plan for extended follow-up periods to capture meaningful longitudinal patterns in both trait stability and behavioral change .
How might genomic data integration enhance future extensions of CLPS-type research?
While the original CLPS did not integrate genomic data, contemporary research platforms like the All of Us Researcher Workbench demonstrate the potential value of leveraging "extensive genomic and phenotypic data" in personality research. Future extensions of CLPS-type studies could incorporate genetic markers to identify biological underpinnings of the stable personality traits identified in the original research, potentially leading to more targeted treatment approaches .
Product Science Overview
Colipase is a small protein that plays a crucial role in the digestion of dietary fats. It is a cofactor for pancreatic lipase, an enzyme responsible for breaking down triglycerides into free fatty acids and monoglycerides. Without colipase, pancreatic lipase cannot effectively anchor to the lipid-water interface, which is essential for its activity. Colipase is produced in the pancreas and is secreted into the small intestine, where it facilitates the digestion of fats by stabilizing the active conformation of pancreatic lipase.
Colipase belongs to the colipase family and has a molecular mass of approximately 11.5 kDa . It is characterized by five conserved disulfide bonds that contribute to its stability and functionality. The protein structure of colipase allows it to bind noncovalently to the surface of lipid micelles, counteracting the destabilizing influence of intestinal bile salts . This binding is essential for the proper functioning of pancreatic lipase, as bile salts can inhibit the enzyme by washing it off the lipid surface.
Recombinant human colipase can be produced using various expression systems, including Escherichia coli (E. coli) and baculovirus-insect cells. The process typically involves the following steps:
- Gene Cloning: The gene encoding human colipase is cloned into an appropriate expression vector.
- Transformation: The vector is introduced into the host cells (e.g., E. coli or insect cells).
- Expression: The host cells are cultured under conditions that induce the expression of the recombinant protein.
- Purification: The recombinant colipase is purified using techniques such as affinity chromatography, which may involve tags like His-tag for easier purification .
For example, in one study, recombinant human pancreatic lipase (recHPL) was successfully prepared from E. coli using a short Strep-tag II (ST II). The recHPL-ST II was solubilized using 8 M urea from the E. coli lysate and purified on a Strep-Tactin-Sepharose column .
Recombinant human colipase is used in various research and clinical applications. It is essential for studying the mechanisms of lipid digestion and the role of pancreatic lipase in metabolic processes. Additionally, recombinant colipase can be used in enzyme replacement therapies for individuals with pancreatic insufficiency, where the pancreas does not produce enough digestive enzymes.
