Cofactors_and_coenzymes_M2P_202425.pptx

COENZYMES AND COFACTORS M2P Fall 2024 Wendy S. Innis, Ph.D. [email protected]  SESSION OBJECTIVES Describe coenzyme, cofactor, prosthetic group, apoenzyme, and holoenzyme Describe the role of vitamins as coenzymes Identify water- and lipid-soluble vi...

COENZYMES AND COFACTORS M2P Fall 2024 Wendy S. Innis, Ph.D. [email protected]  SESSION OBJECTIVES Describe coenzyme, cofactor, prosthetic group, apoenzyme, and holoenzyme Describe the role of vitamins as coenzymes Identify water- and lipid-soluble vitamins Describe the regulatory mechanisms of trace metal homeostasis Predict the biochemical consequences of enzyme deficiencies in trace metal homeostasis Summarize enzyme deficiencies in copper homeostasis  Dietary nutrients Macronutrients Micronutrients Carbs Fat Proteins Vitamins Minerals Essentia Essenti Water Lipid Electrolytes Trace l fatty al soluble soluble (macroelements) minerals acids AAs Linoleic Intracellu Extracellu Cooper, acid Vit C, Iron, Zinc, WHIM A, D, lar lar Linolen B Selenium, ic acid VK LFT vitami E, K K+, Mg2+, Na+, ns phosph Manganes EPA Ca2+, ate, e, Iodine, DHA sulfate Cl- Cobalt ESSENTIAL NUTRIENTS: Nonessential – Can be synthesized by body (mammals), but or sometimes not in sufficient quantity for optimal growth and health Essential – Cannot be synthesized by most mammals, must be obtained from food Conditionally essential – in times of illness and stress; particular times of development EPA – eicosapentaenoic a DHA – docosahexaenoic  Dietary nutrients Macronutrients Micronutrients Carbs Fat Proteins Vitamins Minerals Essentia Essenti Water Lipid Electrolytes Trace l fatty al soluble soluble (macroelements) minerals acids AAs Linoleic Intracellu Extracellu Cooper, acid Vit C, Iron, Zinc, WHIM A, D, lar lar Linolen B Selenium, ic acid VK LFT vitami E, K K+, Mg2+, Na+, ns phosph Manganes EPA Ca2+, ate, e, Iodine, DHA sulfate Cl- Cobalt ESSENTIAL NUTRIENTS: AMINO ACIDS On a WHIM, VK made a LFT turn Conditionally essential in children and during pregnancy due to high rate of protein synthesis: Arg and His Conditionally essential: Tyr and Cys due to genetic deficiency or malnutrition Nonessential – Can be synthesized by body (mammals), but sometimes not in sufficient quantity for optimal growth and health Essential – Cannot be synthesized by most mammals, must be obtained from food Conditionally essential – in times of illness and stress; particular times of development DEFICIENCY AND TOXICITY Micronutrients are essential for cellular homeostasis Cannot be synthesized by the body and must be acquired through the diet Tightly regulated Excess levels can be toxic  VITAMINS Essential organic substances classified as water-soluble or fat- soluble Do not supply energy Aid in growth and maintenance of tissues Water soluble vitamins serve as coenzymes for many enzymes of energy metabolism, and as antioxidants Transported directly through the bloodstream Less likely to cause toxicity because they are not stored (except B2) …More on this in GI I… Review table uploaded on LEO COFACTORS Required factor for an enzyme that forms an intermolecular (sometimes covalent) bond with the enzyme or substrate during the reaction Metal ions (Zn, Fe, Mg, Ca) Organic coenzymes Organometallic Most coenzymes are vitamins or derived from vitamins Cofactor-requiring enzymes initially synthesized as apoenzymes Required for catalysis Cofactors that are covalently or very tightly bound to nonenzyme proteins are usually called prosthetic groups. A prosthetic group usually does not dissociate from a protein until the protein is degraded TWO GENERAL CLASSES OF COENZYMES Activation-transfer coenzymes Usually participate directly in catalysis by forming a covalent bond Characteristics: two groups in coenzyme -- a functional group that forms a covalent bond with the substrate, and a group that binds tightly to the E Gives the E additional specificity for substrates, and additional catalytic power Oxidation-reduction coenzymes Coenzyme has unique functional group that accepts and donates electrons, and is specific for the “form” of electrons it transfers (e.g., hydride ions, hydrogen atoms, oxygen) ACTIVATION-TRANSFER COENZYMES Thiamine pyrophosphate (TPP) derived from vitamin B1 (thiamin) Primarily involved in the oxidation of α-keto acids; decarboxylation rxns Reactive thiamin carbon forms a covalent bond with a substrate keto group while cleaving the adjacent carbon–carbon bond. Generates better nucleophilic attacking group by a basic amino acid residue in the enzyme that removes the dissociable proton Later in the reaction, the enzyme returns the proton Alcohol inhibits B1 absorption by damaging the lining of the intestine [Pyruvate dehydrogenase complex reaction sequence] ACTIVATION-TRANSFER contains an adenosine COENZYMES 3′,5′-bisphosphate that binds reversibly, but tightly, to a site on an enzyme CoA, biotin, and pyridoxal phosphate are also activation-transfer coenzymes synthesized from vitamins CoA synthesized from pantothenate (B5) Biocytin from biotin (B7) Pyridoxal phosphate (PLP) from covalently bonded pyridoxine (B6) to a lysine in carboxylases and functions only in carboxylation reactions  REDOX COENZYMES Lactate loses 2e- NAD+ from niacin (B3) and ATP FAD (next slide) from riboflavin (B 2) Do not form covalent bonds with the substrate Unique functional group accepts and donates electrons Specific for the form of electrons it transfers Other oxidation–reduction coenzymes (Vitamin C, E) work with metals to transfer single electrons to oxygen Vitamin deficiencies affect enzyme activity! ONE-CARBON TRANSFER COENZYMES Carry and transfer one-carbon groups required for amino acid and purine synthesis Folate (B9) exists in many chemical forms Coenzyme form is tetrahydrofolate (FH4) Participates in production of 1-carbon units Vitamin B12 Corrin ring coordinated with cobalt TRACE MINERALS Only very small amounts,