Lecture 5

Fall 2015 BSC203/BIO132

By

M. Jawad Khan, PhD

Course Outline

• General chemistry including atomic nature of matter, molecules, principles of chemical reactions, stochiometry, acids and bases, oxidation-reduction, water as a solvent, pH, and buffers.

• Structure and function of biomolecules, including structure and function of proteins (amino acids, peptides and, enzymes including classification and how it works), protein conjugates, carbohydrates and glycol-conjugates, nucleosides, nucleotides and nucleic acids, lipids (triglycerols, phospholipids, waxes, sphingolipids, glycolipids, steroids) and nature of biological membranes (lipid bilayers), prostaglandins, leukotrienes, vitamins, hormones, co-enzymes, co-factors.

•

Holoenzyme and Apoenzyme

• Holoenzyme – Complex of protein and prosthetic groups

– Catalytically active

• Apoenzyme – The enzyme without the prosthetic groups

– Catalytically inactive

Types of cofactors

•  Some enzymes require cofactors for activity

(1) Essential ions (mostly metal ions)

(2) Coenzymes (organic compounds)

Types of cofactors

inactive) (

active) (

)protein only(

Holoenzyme

+ Cofactor Apoenzyme

Cofactors and Coenzymes Cosubstrates:

- Altered in reaction and regenerated to original structure in subsequent reaction

- Disassociated from active site

- Shuttle chemical groups among different enzyme reactions.

Prosthetic groups:

- Remains bound to enzyme

- Must return to original form

Both cosubstrates and prosthetic groups supply reactive groups not present on amino acid side chains

Cofactors and Coenzymes Examples:

1) Metabolite coenzymes – synthesized from common metabolites

2) Nucleoside triphosphates – (ATP) can donate phosphates, pyrophosphates, adenosyl grroups

3) S-adenosylmethionine (SAM) – donates methyl groups

4) Nucleotide sugars (uridine diphosphate glucose = UDP-glucose) - transfer sugars in carbohydrate metabolism

Cofactors and Coenzymes • Many Enzymes Require Inorganic Cations

• Enzymes requiring metal ions for full activity:

(1) Metal-activated enzymes

(2) Metalloenzymes

Example: Carbonic anhydrase

• A metalloenzyme

• Zinc ion promotes the ionization of bound H2O.

Resulting OH- attacks carbon of CO2

Vitamin-Derived Coenzymes

• Animals rely on plants and microorganisms for vitamin sources (meat supplies vitamins also)

•Must be obtained from diet  

•Synthesized by microorganisms and plants  

• Most vitamins must be enzymatically transformed to the coenzyme

• Vitamin deficiencies lead to disease state

Vitamin-Derived Coenzymes Vitamin Coenzyme Ascorbic acid (C) not a coenzyme

Niacin (B3) NAD(P)+/NAD(P)H

Riboflavin (B2) FMN & FAD

Thiamin (B1) Thiamin-pyrophosphate

Pyridoxal (B6) Pyridoxal phosphate

Biotin (B7) Biotin

Folate (B9) Tetrahydrafolate

Cobalamin (B12) adenosyl-and methylcobalamin

Vitamin A Retinal Vitamin K Vitamin K

Pantothenate (B5) Coenzyme A

Vitamins: Definition • Organic compound found in foods

• Required in small amounts

• Required in the diet (dietary essential)

• Proven to be required for health, growth, and reproduction

– Deficiency syndrome identified

Vitamin Nomenclature

• Fat soluble “A” & Water soluble “B”

• “Vital amines”

– vitamines = vitamins

• Vitamin B “complex” – Collection of water soluble vitamins that function as enzyme

cofactors

• Vitamin C

• Vitamins D and E

• Mistaken Vitamins

Fat and Water Soluble Vitamins

Fat Soluble Vitamins (A, D, E, K) • Soluble in lipids and

solvents • Excess stored and not

excreted • Excess may be toxic • Deficiency slow to

develop

Fat and Water Soluble Vitamins

Water Soluble Vitamins

• B vitamins, C

• Soluble in water

• Excess excreted in urine, little stored

• Generally less toxic

• Deficiency develops quickly

General Functions of Vitamins

Hormones

–Vitamin D • Calcium homeostasis

–Vitamin A • Cell division and development

General Functions of Vitamins

Non-specific chemical reactions

• Vitamin E –Antioxidant

• Vitamin C –Chemical reducing agent

General Functions of Vitamins

Coenzymes or Cofactors

– Chemicals that assist enzymes to function as catalysts • B vitamins

• Vitamin C, A, K