NST103_Part4_Lecture5_ROS_VitaminC_and_E

NST103 Nutrient Function and Metabolism

Unit 4: Metabolism and Function of Select Micronutrients

Lecture 5: ROS, Vitamin C and Vitamin E

Course Overview

  • Part 4 of the course will cover:

    • Lecture 1: Overview - Importance of vitamins

    • Lecture 2: Iron

    • Lecture 3: Vitamins B9 and B12

    • Lecture 4: Calcium, Phosphorus, Vitamin D, and bones

    • Lecture 5: Reactive Oxygen Species (ROS), Vitamin C, and Vitamin E

    • Lecture 6: Vitamin supplements and health with a review of evidence

Learning Objectives for Today's Lecture

  • Understand what Reactive Oxygen Species (ROS) are

  • Learn the function of Vitamin C:

    • As a cofactor/substrate for enzymes

    • As a ROS scavenger

  • Understand the function of Vitamin E:

    • As a ROS scavenger

  • Required reading: Stipanuk and Caudill, chapters on Vitamin C and Vitamin E.

Outline of the Lecture

  • Introduction to Reactive Oxygen Species (ROS)

    • Types and sources of ROS

    • Mechanisms of damage caused by ROS

    • ROS detoxification mechanisms

  • Vitamin C

    • Discovery and functions

    • Role as an enzyme cofactor and ROS scavenger

  • Vitamin E

    • Discovery and functions

    • Role as an ROS scavenger

Reactive Oxygen Species (ROS)

  • Definition and Types:

    • Include hydroxide radical (•OH), hydrogen peroxide (H2O2), and superoxide (O2•–)

    • Reactivity is highest in the hydroxide radical (•OH) followed by superoxide (O2•–) and then hydrogen peroxide (H2O2).

  • Formation:

    • Formed by one-electron transfer reaction transitioning from water redox state to oxygen.

  • Dangers:

    • ROS can damage DNA, enzymes, and cellular membranes.

    • Many organisms struggle to survive at oxygen concentrations above 21% due to increased ROS production.

  • Beneficial Roles:

    • ROS can be used by neutrophils to kill microbes and work as cell signaling molecules.

Specific Types of ROS

Hydroxyl Radical (•OH)

  • Formed from the reaction of Fe2+ and H2O2 during Fenton reactions.

  • Highly reactive, leading to almost immediate interactions with the first encountered molecule.

Superoxide (O2•–)

  • Generated via one-electron reduction of O2 through FADH2 or Fe2+.

  • Selective reactions with certain enzymes can lead to the inactivation of FeS cluster enzymes, significantly affecting microbial growth.

Hydrogen Peroxide (H2O2)

  • Can form from various sources, including superoxide detoxification.

  • Less reactive than other ROS, but can lead to production of highly reactive •OH through Fenton reaction when reacting with Fe2+.

ROS Defense Mechanisms in Cells

  • Cells have several defense mechanisms to manage ROS, including:

    • Superoxide Dismutase (SOD)

    • Catalase (Cat)

    • Glutathione Peroxidase (GPX)

    • Peroxiredoxin (PRDX)

    • Vitamins C and E

  • These proteins are some of the most abundant in cells, illustrating the importance of managing ROS levels.

Historical Context of ROS Defense Systems

  • ROS defense mechanisms are conserved across all life forms, suggesting that the Last Universal Common Ancestor (LUCA) likely had such systems over 3.7 billion years ago, even before the presence of oxygen in the atmosphere.

Vitamin C

Discovery and Historical Perspective

  • Deficiency of Vitamin C causes scurvy, leading to symptoms like bleeding, corkscrew hair, and joint pain.

  • Historically significant in contexts such as maritime voyages, notably affecting sailors.

  • Significant studies include Lind's clinical trial on lime juice, which was a pivotal moment in understanding scurvy treatment (mid-1700s).

Synthesis and Transport

  • Humans lack one enzyme, L-gulonolactone oxidase (GULO), necessary for Vitamin C biosynthesis, which contributes to dietary requirements for this vitamin.

  • Transport mechanisms involve sodium-coupled transporters and glucose transporters for cellular entrance of ascorbic acid (AA).

Functions and Redox Reactions

  • Vitamin C functions include acting as an ROS scavenger and participating in enzymatic processes essential for collagen biosynthesis and DNA demethylation.

  • It has important catalytic roles, supporting various oxygenases to facilitate necessary metabolic reactions.

Vitamin E

Discovery

  • Vitamin E was discovered in 1922. Its role was identified as necessary for reproductive success in rats.

  • Purification occurred in 1936 by Evans, solidifying its identity and function as a vital nutrient.

Functional Role in ROS Defense

  • Its mechanism involves intercepting lipid radicals, crucial for maintaining the integrity of polyunsaturated lipids that are prone to oxidative damage.

  • Vitamin E acts by forming stable radicals that inhibit chain reactions resulting from lipid peroxidation.

Summary of Key Functions and Mechanisms

  • Both Vitamin C and Vitamin E are potent antioxidants that work to mitigate oxidative stress.

  • They are involved in vital processes that preserve cellular and overall organism health through ROS scavenging abilities.