Chem 438 - Introductory Biochemistry - Spring 2013

Lecture Notes:

Enzyme Catalysis, cont.

Chymotrypsin

(digestive enzyme).

Zymogens

define—precursor protein has peptide covering active site, activated by having it hydrolyzed off. Examples. [Figure 6.22; 6.23a = zymogen, b = enzyme]

Serine Proteases [Figure 6.24, 6.25]
Asp-His-Ser catalytic triad in serine proteases. [Figure 6.26, 6.27]
Mechanism, as noted in [Figure 6.28]

Introduction to Vitamins and Cofactors

Terms:

Cofactor: a co-catalyst required for enzyme activity.
- coenzyme - a dissociable cofactor.
- prosthetic group - non-dissociable cofactor.
- metal ion - a metal cofactor.
Vitamin: a required micro-nutrient (organism cannot synthesize adequate quantities for normal health - may vary during life-cycle).
- water soluble - not stored, generally no problem with overdose.
- lipid soluble - stored, often toxic with overdose.

Let's start with a brief overview of the names, structures and physiological functions of the common vitamins as shown on the Slide: Niacin, Riboflavin [B₂], Thiamine, Pantothenic acid, Biotin, Pyridoxal [B₆], Folic acid, Lipoic acid, Cobalamin [B₁₂], L-Ascorbic acid [C], and the lipid soluble vitamins A, D, E, and K). Fun facts:

Niacin deficiency gives rise to pellagra (swollen tongue, dermatitis, neurologic and gastro-intestinal disturbances).
Thiamine deficiency gives rise to berberi (extensive damage to nervous and circulatory systems, muscle wasting and edema - once common in Asia due to the comsumption of polished rice, which is low in nutrients, as a staple.).
Folate and Cobalamin deficiency both give rise to megaloblastic anemia, however cobalamin deficiency also results in irreversible CNS damage.

In contrast to most water soluble vitamins, the lipid soluble vitamins can be taken in excess, with toxic results:
- Excess vitamin D (actually a hormone) causes excess Ca²⁺ buildup with precipitation to form kidney stones and precipitates in tissues. Deficiency results in rickets.

Data and most vitamin structures courtesy of *Wikipedia Commons* article on Vitamins and links to individual vitamins
Vitamin generic descriptor name	Vitamer chemical name(s) (list not complete	Solubility	Structure Diagram	Recommended dietary allowances (male, age 19–70)[	Deficiency disease	Upper Intake Level (UL/day)	Overdose disease
Vitamin B1	Thiamine	Water		1.2 mg	Beriberi, Wernicke-Korsakoff syndrome	N/D[20]	Drowsiness or muscle relaxation with large doses.[21]
Vitamin B2	Riboflavin	Water		1.3 mg	Ariboflavinosis	N/D
Vitamin B3	Niacin, niacinamide	Water		16.0 mg	Pellagra	35.0 mg	Liver damage (doses > 2g/day)[22] and other problems
Vitamin B5	Pantothenic acid	Water		5.0 mg[23]	Paresthesia	N/D	Diarrhea; possibly nausea and heartburn.[24]
Vitamin B6	Pyridoxine, pyridoxamine, pyridoxal	Water		1.3–1.7 mg	Anemia[25] peripheral neuropathy.	100 mg	Impairment of proprioception, nerve damage (doses > 100 mg/day)
Vitamin B7	Biotin	Water		30.0 µg	Dermatitis, enteritis	N/D
Vitamin B9	Folic acid, folinic acid	Water		400 µg	Megaloblast and Deficiency during pregnancy is associated with birth defects, such as neural tube defects	1,000 µg	May mask symptoms of vitamin B12 deficiency; other effects.
Vitamin B12	Cyanocobalamin, hydroxycobalamin, methylcobalamin	Water		2.4 µg	Megaloblastic anemia[26]	N/D	Acne-like rash [causality is not conclusively established].
Vitamin C	Ascorbic acid	Water		90.0 mg	Scurvy	2,000 mg	Vitamin C megadosage
Vitamin A	Retinol, retinal, and four carotenoids including beta carotene	Fat		900 µg	Night-blindness, Hyperkeratosis, and Keratomalacia[19]	3,000 µg	Hypervitaminosis A
Vitamin D	Ergocalciferol, cholecalciferol	Fat		5.0 µg–10 µg[27]	Rickets and Osteomalacia	50 µg	Hypervitaminosis D
Vitamin E	Tocopherols, tocotrienols	Fat		15.0 mg	Deficiency is very rare; mild hemolytic anemia in newborn infants.[28]	1,000 mg	Increased congestive heart failure seen in one large randomized study.[29]
Vitamin K	phylloquinone, menaquinones	Fat		120 µg	Bleeding diathesis	N/D	Increases coagulation in patients taking warfarin.[30]