Cholesterol and Bile Salts Overview
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Cholesterol and Bile Salts Overview

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Questions and Answers

What is the primary function of statins in cholesterol regulation?

  • Enhance cholesterol absorption
  • Increase bile acid production
  • Stimulate liver function
  • Inhibit HMG-CoA reductase (correct)
  • Where are primary bile salts synthesized?

  • Intestine
  • Gallbladder
  • Pancreas
  • Liver (correct)
  • How do secondary bile salts differ from primary bile salts?

  • They are stored in the gallbladder
  • They are formed by bacterial action in the intestine (correct)
  • They are more polar than primary bile salts
  • They are synthesized in the liver from cholesterol
  • Which enzyme is primarily involved in the synthesis of sphingosine?

    <p>Sphingosine synthase</p> Signup and view all the answers

    What is the result of a deficiency in the enzymes responsible for sphingolipid degradation?

    <p>Buildup of specific sphingolipids</p> Signup and view all the answers

    What is the role of cholestyramine in cholesterol management?

    <p>It acts as a bile salt sequestrant</p> Signup and view all the answers

    What characterizes sphingolipidosis diseases such as Niemann-Pick and Tay-Sachs?

    <p>Accumulation of specific sphingolipids</p> Signup and view all the answers

    What physiological process occurs with bile acids after they are secreted into the intestine?

    <p>Deconjugation and dehydroxylation</p> Signup and view all the answers

    What is the primary role of NADPH produced in the Pentose Phosphate Pathway?

    <p>Biosynthetic reactions and oxidative stress prevention</p> Signup and view all the answers

    Which phase of the Pentose Phosphate Pathway is characterized by irreversible reactions?

    <p>Oxidative phase</p> Signup and view all the answers

    What is the consequence of glucose-6-phosphate dehydrogenase deficiency?

    <p>Hemolysis during oxidative stress</p> Signup and view all the answers

    Which sugar component is specifically associated with nucleotide biosynthesis?

    <p>Ribose-5-phosphate</p> Signup and view all the answers

    Which enzyme is a critical regulator of the oxidative phase in the Pentose Phosphate Pathway?

    <p>Glucose-6-phosphate dehydrogenase</p> Signup and view all the answers

    What is one role of UDP-glucose in metabolism?

    <p>Synthesis of glucuronides</p> Signup and view all the answers

    How do reactive oxygen species (ROS) generated by NADPH oxidase impact pathogens?

    <p>They are cytocidal and help kill invading pathogens</p> Signup and view all the answers

    What happens to ribose-5-phosphate when only NADPH is needed?

    <p>It is diverted into glycolytic intermediates</p> Signup and view all the answers

    What is a likely consequence of the decrease in superoxide dismutase (SOD) levels in periodontal patients?

    <p>Accumulation of reactive oxidant species</p> Signup and view all the answers

    Which metabolic changes occur due to insulin insufficiency?

    <p>Increase in gluconeogenesis</p> Signup and view all the answers

    What differentiates Type 1 diabetes mellitus from Type 2 diabetes mellitus regarding insulin production?

    <p>Type 1 has low or absent endogenous insulin</p> Signup and view all the answers

    In periodontal disease, the local redox imbalance primarily contributes to which of the following?

    <p>Onset and progression of periodontal diseases</p> Signup and view all the answers

    What is a common consequence of elevated glucose levels in diabetic patients?

    <p>Increased breakdown of triglycerides</p> Signup and view all the answers

    Which of the following statements is true about Type 2 diabetes mellitus?

    <p>Commonly associated with obesity</p> Signup and view all the answers

    What role do metal ions like Cu, Mn, and Zn play in relation to periodontal disease?

    <p>Decrease antioxidant enzyme activity</p> Signup and view all the answers

    What is a characteristic feature of ketoacidosis in diabetes?

    <p>Results from the absence of insulin production</p> Signup and view all the answers

    What is a common symptom associated with hereditary hemorrhagic telangiectasia?

    <p>Frequent nosebleeds</p> Signup and view all the answers

    Which type of neurofibromatosis is characterized by the presence of bilateral vestibular schwannomas?

    <p>NF2</p> Signup and view all the answers

    In which genetic disorder does defective collagen production primarily lead to fragile bones?

    <p>Osteogenesis imperfecta</p> Signup and view all the answers

    What is a notable management strategy for basal cell nevus syndrome?

    <p>Regular skin checks for early detection of skin cancers</p> Signup and view all the answers

    What is a symptom associated with both osteogenesis imperfecta and hereditary hemorrhagic telangiectasia?

    <p>Risk of internal bleeding</p> Signup and view all the answers

    What role do receptors for AGEs play in the body?

    <p>They mediate hyper inflammatory response.</p> Signup and view all the answers

    What is the main advantage of using fluorescence in situ hybridization (FISH) over karyotyping?

    <p>FISH detects structural abnormalities at a higher resolution.</p> Signup and view all the answers

    Which genetic disorder is associated with a deletion in the maternal chromosome 15?

    <p>Angelman syndrome</p> Signup and view all the answers

    What is the primary purpose of array comparative genomic hybridization (array CGH)?

    <p>To analyze the entire genome for copy number variations.</p> Signup and view all the answers

    Which type of chromosomal alteration involves a segment of a chromosome being reversed end to end?

    <p>Inversion</p> Signup and view all the answers

    How does imprinting affect gene expression?

    <p>It causes genes to be expressed based on parent-of-origin.</p> Signup and view all the answers

    What is a common result of chromosome translocations?

    <p>Disrupts gene function due to loss of genetic material.</p> Signup and view all the answers

    Which of the following techniques is most suitable for identifying small deletions or duplications in genetic disorders?

    <p>Array Comparative Genomic Hybridization (array CGH)</p> Signup and view all the answers

    Study Notes

    Cholesterol to Bile Salts

    • Cholesterol is only removed from the body through conversion to bile salts, which occurs solely in the liver.
    • Primary bile salts are directly synthesized from cholesterol within the human liver.
    • Conjugation of bile salts enhances their emulsification properties by lowering their pKa.
    • Bile salts are stored in the gallbladder and released into the intestines upon stimulation, aiding digestion.

    Inhibition of Cholesterol Synthesis by Statins

    • Statins act as competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis.
    • This inhibition effectively reduces cholesterol synthesis.
    • Cholestyramine, a bile salt sequestrant, binds to bile salts in the intestines preventing reabsorption.
    • This interrupts the enterohepatic circulation, further reducing cholesterol levels.

    Enterohepatic System

    • The enterohepatic system continuously cycles cholesterol through the liver, gallbladder, and intestines for digestion.
    • Bile salts are either reabsorbed into the liver or excreted in feces, providing a crucial pathway for cholesterol removal.

    LCAT & ACAT

    • Both LCAT and ACAT are enzymes crucial for the esterification of cholesterol.
    • LCAT functions in the bloodstream, while ACAT operates within cells.

    Primary and Secondary Bile Acids

    • Primary bile salts are synthesized in the liver.
    • Bacterial flora in the intestines can deconjugate and dehydroxylate primary bile salts, creating secondary bile salts.
    • Secondary bile salts, like lithocholic acid, are more nonpolar and readily reabsorbed.
    • Secondary bile salts are more prone to excretion than primary bile salts.

    Sphingolipid Synthesis & Degradation

    • Sphingosine, synthesized on the endoplasmic reticulum, is a crucial precursor for sphingolipids.
    • Sphingomyelin synthesis is catalyzed by sphingomyelin synthases.
    • Deficiencies in sphingolipid degradation enzymes result in sphingolipidoses, leading to the accumulation of sphingolipids.

    Sphingolipidoses

    • Sphingolipid diseases include Niemann-Pick, Tay-Sachs, and Gaucher's disease.
    • These disorders involve an accumulation of specific sphingolipids within cells, leading to dysfunction.
    • The underlying cause is a missing or defective enzyme involved in sphingolipid degradation.

    Pentose Phosphate Pathway (PPP)

    • The PPP generates:
      • NADPH, a strong reductant vital for reductive biosynthesis, glutathione reduction to scavenge ROS, and ROS production in phagocytes.
      • Ribose-5-phosphate, crucial for nucleotide biosynthesis (DNA/RNA, cell growth) leading to new ATP and cofactors.
    • The PPP's oxidative phase is irreversible, while the non-oxidative phase is reversible, supporting cellular needs.
    • In red blood cells, the PPP scavenges reactive oxygen species (ROS).
    • Phagocytes utilize the PPP for respiratory bursts, producing ROS for pathogen destruction.

    Glucose-6-Phosphate Dehydrogenase Deficiency

    • Deficiencies in glucose-6-phosphate dehydrogenase (G6PD) affect the PPP, resulting in hemolysis during oxidative stress.
    • Oxidative stressors, triggered by antimalarial agents, infections, or fava beans, disrupt glutathione defense.
    • This leads to increased oxidative damage, causing hemolytic anemia.

    UDP-Sugars and their Roles

    • UDP-sugars, central to synthesis of various macromolecules:
      • Lactose, glycoproteins, glycolipids, proteoglycans, and glucuronides.
    • UDP-glucose acts as a glucose donor for glycogen and glycoproteins, and can be epimerized to UDP-galactose.
    • Transferase enzymes mediate the incorporation of UDP-sugars into target molecules.
    • UDP-glucuronate, derived from UDP-glucose, is essential for detoxification, bilirubin conjugation, steroid excretion, and reducing ROS.

    Role of ROS in Periodontal Disease

    • Periodontal disease involves a redox imbalance favoring oxidative stress.
    • Superoxide dismutase (SOD) levels are significantly reduced in saliva and serum of periodontal patients.
    • Local SOD plays a crucial role in controlling redox status in periodontitis.
    • Increased ROS levels contribute to the onset and progression of periodontal disease.

    Insulin Insufficiency and Metabolic Changes

    • Insulin insufficiency triggers a cascade of metabolic changes, including:
      • Increased: glucagon, blood glucose, fatty acids, amino acids, protein breakdown, fatty acid oxidation, gluconeogenesis, and lipolysis of triglycerides.
      • Decreased: glycolysis, fatty acid synthesis, protein synthesis, and lipolysis of triglycerides in VLDLs and chylomicrons.

    Type 1 and Type 2 Diabetes Mellitus

    • Type 1: Autoimmune destruction of pancreatic beta cells leads to insulin deficiency.
      • Diagnosed at a young age, characterized by ketoacidosis, and requires exogenous insulin supplementation.
    • Type 2: Insulin resistance develops primarily due to obesity.
      • Diagnosed mostly in adults, often linked to obesity, and may initially involve normal or even increased insulin production.

    Complications of Diabetes Mellitus (DM)

    • Elevated blood glucose levels lead to:
      • Increased glycogenolysis and gluconeogenesis.
      • Reduced glucose uptake (via GLUT4) and glycolysis.
      • Enhanced lipid catabolism (increased triglyceride lipolysis and beta-oxidation due to hormone-sensitive lipase activity).
    • Advanced Glycation End-products (AGEs) accumulate, promoting inflammatory responses.
    • Good dental health is crucial for managing diabetes, as periodontal therapy can improve glycemic control.

    Chromosomal Variations and Disorders

    • Deletions: Loss of a chromosome segment can lead to disorders like Angelman syndrome (maternal chromosome 15) and Prader-Willi syndrome (paternal chromosome 15).
    • Duplications: Extra copies of a chromosomal segment can cause various syndromes depending on the specific region.
    • Inversions: A segment of a chromosome is reversed end to end, potentially disrupting gene function.
    • Translocations: A segment of one chromosome breaks off and attaches to another, which can be balanced or unbalanced.

    Imprinting and Disease Expression

    • Imprinting refers to the epigenetic phenomenon where gene expression is parent-of-origin-specific.
    • Certain genes are only expressed from the mother's copy, while others are only expressed from the father's copy.
    • Imprinting can affect disease manifestation and severity.

    Hereditary Hemorrhagic Telangiectasia (HHT)

    • A genetic disorder causing abnormal blood vessel formation (telangiectasias and AVMs).
    • Symptoms include frequent nosebleeds, skin and mucosal telangiectasias, and internal bleeding.
    • Autosomal dominant inheritance pattern.

    Neurofibromatosis

    • Defined by the growth of benign tumors (neurofibromas) on nerves and skin.
    • Two main types:
      • NF1: More common, featuring café-au-lait spots, neurofibromas, and freckling.
      • NF2: Characterized by bilateral vestibular schwannomas (acoustic neuromas), causing hearing loss.
    • Autosomal dominant inheritance.

    Osteogenesis Imperfecta (OI)

    • A group of genetic disorders leading to brittle bones due to defective collagen production.
    • Symptoms include frequent fractures, blue sclera, dental imperfections, and hearing loss.
    • Multiple types with varying severity, typically autosomal dominant inheritance, but some forms are autosomal recessive.

    Basal Cell Nevus Syndrome (BCNS)

    • A genetic condition increasing susceptibility to various neoplasms, especially basal cell carcinomas.
    • Symptoms include multiple BCCs, jaw cysts, palmar and plantar pits, and skeletal abnormalities.
    • Autosomal dominant inheritance.

    Periodontal Disease and Genetics

    • Genetic predisposition plays a role in the development of periodontal disease.
    • Variations in genes related to immune response, collagen synthesis, and bone metabolism can influence disease risk.
    • Family history of periodontal disease can also increase individual susceptibility.

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    Description

    This quiz covers the conversion of cholesterol to bile salts, focusing on the synthesis in the liver and the role of bile salts in digestion. It also addresses the impact of statins on cholesterol synthesis and the enterohepatic system's function in cholesterol cycling.

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