thomas o. henderson, ph. d. professor emeritus dept. of biochemistry & molecular genetics...

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Thomas O. Henderson, Ph. D. Thomas O. Henderson, Ph. D. Professor Emeritus Professor Emeritus Dept. of Biochemistry & Dept. of Biochemistry & Molecular Genetics Molecular Genetics Office: Office: 321 CMW 321 CMW Phone: Phone: 6-5978 6-5978 email: [email protected] email: [email protected]

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Page 1: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Thomas O. Henderson, Ph. D.Thomas O. Henderson, Ph. D.

Professor EmeritusProfessor Emeritus

Dept. of Biochemistry & Dept. of Biochemistry &

Molecular GeneticsMolecular Genetics• Office:Office: 321 CMW321 CMW• Phone:Phone: 6-59786-5978• email: [email protected]: [email protected]

Page 2: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

MacronutrientsMacronutrients

• Lecture 2 Lecture 2 Carbohydrates & FiberCarbohydrates & Fiber

• Lecture 3Lecture 3 Fats (Lipids)Fats (Lipids)

• Lecture 4Lecture 4 ProteinsProteins

Page 3: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

From MMWR 53, No. 4; February 6, 2004

Page 4: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Macronutrients IMacronutrients I

• OverviewOverview• CarbohydratesCarbohydrates• FiberFiber

Page 5: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

2002 IOM-FNB Guidelines for 2002 IOM-FNB Guidelines for MacronutrientsMacronutrients

• Goal of new recommendation “to meet the body’s daily energy and nutritional needs while minimizing risks for chronic disease.”

• Guidelines set for macronutrients: carbohydrates, fats, proteins

• For first time, DRI’s set for dietary fiber and essential fatty acids (n-3 & n-6)

• Guidelines set for exercise

Page 6: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Acceptable Macronutrient Acceptable Macronutrient Distribution Range (AMDR)Distribution Range (AMDR)

• AMDR just another way of stating the % of calories from a given class of macronutrient

• 2002 recs adults ≥19 years:

% of daily calories

Carbohydrates 45 - 65

Fats 20 - 35%

Proteins 10 - 35% ≤25% of total calories from “added sugar”

Page 7: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

AMDR (continued)

• Recommendations more flexible than in past

• Ranges set so that total dietary intake would be of breadth and quality to insure intake of essential nutrients (i.e., vitamins & minerals)

• Diets very low in either carbs or fat likely to be deficient in one or more essential nutrient

Page 8: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

AMDR (continued)

When fat intakes are low and carb intake is

high:

• HDL is reduced

• ratio of plasma cholesterol:HDL increased

• plasma triacylglycerol (TAG) increased

These all consistent with increased risk of

coronary heart disease (CHD; CAD)

Page 9: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

AMDR (continued)

• When fat intakes are high, people gain weight

• Can exacerbate health of persons already susceptible to obesity, particularly risk of CHD and Type II diabetes

• High fat diets usually associated with increased intake of saturated fatty acids

• The latter, in turn, can increase LDL levels and thereby increase risk of CHD

Page 10: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

All Fatty Acids are NOT Equal!

If fat intake is at high end of 20 -35%

range, one would be well advised to

• limit intake of cholesterol and

saturated and trans fatty acids

• replace them with monounsaturated

and polyunsaturated fatty acids

Page 11: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

CarbohydratesCarbohydrates• 2002 IOM-FNB report set RDA for intake of

digestible carbohydrate

• for ages 1 - >70, 130 g/d recommended

• 175 & 210 g/d for lactating and pregnant women, respectively

• for 0 - 6 months, AI set at 60 g/d

• for 7 - 12 months, AI set at 95 g/d

Page 12: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

• RDA (& AI) for carbs based on minimum amount needed to provide glucose for brain function

• Most of us regularly exceed RDA

• AMDR set at 45 - 65% of calories/day

• No more than 25% of calories/day from “added sugars”

• Emphasis should be on obtaining bulk of daily carbs from fruits, vegetables, and minimally processed whole grains and whole grain products

Page 13: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Major Sources of Major Sources of Carbohydrates Carbohydrates

• disaccharides (sucrose, lactose)

• starch (amylose & amylopectin)

• minor, variable amounts of glycogen (in meats), maltose, trehalose (mushrooms), raffinose (legumes)

• very little monosaccharide in natural diet

• increased amounts of added fructose (high-fructose corn syrup or solids)

Page 14: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

MALTOSE SUCROSE

LACTOSE

Glu α(1 → 4) Glu Glu α(1 → 2) Fru

Gal β(1 → 4) Glu

Page 15: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Amylose

Amylopectin

Cellulose(NOT a form

of starch)

Forms of Starch

Page 16: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

On a Food Label, Sugars Include:

brown sugar invert sugar

corn sweetener lactose

corn syrup maltose

fructose molasses

fruit juice concentrate raw sugar

glucose (dextrose) [table] sugar (sucrose)

high-fructose corn syrup syrup

honey

Page 17: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Consequences of chronic elevation in Consequences of chronic elevation in concentration of hexoses in bloodconcentration of hexoses in blood

2 possible consequences are

• enzymatic formation of sugar alcohols

• nonenzymatic glycosylation (“glycation”)

of proteins

Both of these associated with long term

pathologies of nerves, blood vessels,

kidneys, and lens as found in diabetes and

galactosemia

Page 18: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Sugar Sugar AlcoholsAlcohols

• Aldose reductase and polyol

dehydrogenase involved

• Isozymes of aldose reductase found in most

tissues

• Especially high in Schwann cells of

peripheral nerves, kidney papillae, and lens

epithelium

Page 19: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:
Page 20: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Ways in which sugar alcohols cause cell

damage and pathologies not known

However, since they do not diffuse out of

cells very readily, they can cause cell

damage by cellular swelling associated with

osmosis

The enzymatic reactions are reversible so

that favored direction is determined by

substrate/product concentrations (i. e.,

“mass action”)

Page 21: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Protein glycosylation (glycation)Protein glycosylation (glycation)

• nonenzymatic process

• get advanced glycosylation product

formation (“AGE products”) with

proteins

• quite possible that glycosylation of

DNA occurs also

Page 22: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

An estimate of how well a diabetic patient has controlled her/his hyperglycemia over past 5-6 weeks can be made by measuring extent of hemoglobin glycosylation (HbA1c)

• Recall - RBC hemoglobin has lifespan of

~120 days

• Shorter or more recent periods can be

estimated by measuring albumin

glycosylation

Page 23: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Glucose

Protein

Schiff BaseAmadoriProduct

(more stable)

Glucose-DerivedCross-Link

(one kind of product)

Aminoguanineinhibits

Page 24: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Galactose MetabolismGalactose Metabolism

• By far major source of galactose in human

diet is in form of lactose

• Major source of lactose is milk and milk

products

• Major organ involved in galactose

metabolism is liver

• There are several inborn errors involving

metabolism of galactose

Page 25: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Lactase deficiency (aka Hypolactasia)(lactose or milk intolerence)

• In most mammals, including the great majority of humans, lactase activity disappears after weaning or at the latest during adolescence.

• In the case of humans, especially true for Southeast Asians and Africans.

• About 70% of African-Americans, >80% of Chinese and >70% of Mexicans are lactose intolerant

• In contrast, lactase deficiency uncommon in Northwest Europeans such as Scandinavians (~3% of Danes)

Page 26: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

2 types of galactosemia are caused by deficiency or absence of:

D-galactose 1-P uridyltransferase D-galactose 1-P uridyltransferase and

galactokinasegalactokinase

• The first more common (prevalence = 1 in 70,000) than second (prevalence = 1 in 1 x 105) and has far greater clinical importance in terms of associated pathologies, especially in homozygotes

• In Illinois the incidence of the first defect is ~1 in 30,000 live births

Page 27: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Definitions:

Incidence = 1 in n live births

Prevalence = 1 in n people

Page 28: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:
Page 29: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

The pathologies associated with defective D-galactose 1-P uridyl transferase include:

• severe mental retardation, hepatomegaly, cataracts, and non-specific morphological changes in the CNS

• In Illinois, all newborns are screened for galactosemia

• Affected infants MUST be placed on a galactose-free (i. e., milk-free) diet immediately to prevent irreversible damage

Page 30: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Fructose MetabolismFructose Metabolism

• Major sources of fructose in diet are fruits,

honey, sucrose and, now, in form of high

fructose corn syrup or solids as an added

sweetener in soft drinks, candy, etc.

• Fructose -in one form or another- may

account for 30 - 60% of total dietary

carbohydrates for some

• Major organ involved in fructose metabolism

is the liver

Page 31: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

There are two (rare) inherited diseases of fructose metabolism

• Essential fructosuria - caused by deficiency in fructokinase and leads to transitory elevation of blood fructose level and to fructosuria (fructose in the urine)

• Fructose intolerance - MUCH MORE SERIOUS EFFECTS similar to those associated with galactosemia - caused by a defect in fructose-1-P aldolase (aldolase B)

• In fructose intolerance fructose and its sources (sucrose!) must be eliminated from diet

Page 32: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Essential Fructosuria

Fructose Intolerance

Page 33: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

“Baby Bottle” Caries

Page 34: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

“Baby Bottle” Caries. Rampant caries due to use of sugar-sweetened beverages in nursing bottle as a pacifier

From Nutrition in Clinical Dentistry, 3/ed, 1989, A. E. Nizel and A. S. Papas (W. B. Saunders), Fig. 3-7, p. 46.

Page 35: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Glycemic Index (GI)Glycemic Index (GI)Glycemic index of a carbohydrate defined

as incremental area under blood glucose

response curve of a 50g carbohydrate

portion of a test food expressed as a

percentage of the response to the same

amount of carbohydrate from a standard

food (usually glucose or white bread) taken

by the same subject.

An abbreviated table of GI’s found on

p. 8 of Macronutrient I handout

Page 36: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

• In general, carbohydrate-containing foods such as whole grains, legumes, fruits, vegetables have low GI’s

• Amylose form of starch has lower GI than amylopectin

• Broadly speaking about grain products, the greater the processing, the higher the GI

Page 37: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Factor Influencing GIFactor Influencing GINumber of factors influence GI besides amount or type of carbohydrate in a meal.

In a multi-component food or meal, these include:

amount & type of carbohydrate

nature of starch

presence or absence of fat, protein, fiber

how food was prepared

Table of factors influencing GI found on p. 8 of Macronutrient I handout

Page 38: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Diabetes Care 27, Supplement 1,pp. S36 - S46, January 2004

American Diabetes Society issued Position Statement entitled “Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications”

• The panel concluded, “If there are long term effects (of carbohydrate intake) on glycemia and serum lipids, these effects appear to be modest.”

• Their position is that recommendations on intakeof carbohydrates (and monounsaturated fat)should be individualized for each diabetic patient

Page 39: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Dietary FiberDietary Fiber• Defined as nondigestible carbohydrates &

lignin intrinsic and intact in plants

• Functional fiber defined as isolated nondigestible carbohydrates that have been shown to have beneficial effects in humans

• Total fiber: dietary fiber + functional fiber

• AI 38g/d for men ages 14 - 50 y; 25g/d for women ages 19 - 50 y

Tables for Total Fiber DRI (AI) and sources of fiber on p. 9, Macronutrient I handout

Page 40: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

Viscous FiberViscous Fiber

• Some types of fiber form highly viscous solutions (viscous fiber)

• Viscous fibers delay gastric emptying of ingested foods into small intestine

• This produces sensation of fullness

• Delayed gastric emptying also results in reduced postprandial blood glucose levels

Page 41: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

• Intake of even moderate amounts of viscous fiber is associated with lowering plasma cholesterol levels

• They apparently interfere with absorption of dietary fat and cholesterol and enterohepatic circulation of bile acids and cholesterol

Page 42: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:

• Viscous fibers includes pectins, various gums, mixed-linkage β-glycans, psyllium, agar, and carrageenan

• Oat bran, barley, legumes and various vegetables are good sources of viscous fiber

• Isolated fibers or fiber sources that are not viscous (e.g., cellulose, corn and wheat bran) rarely found to lower plasma cholesterol levels

Page 43: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email:
Page 44: Thomas O. Henderson, Ph. D. Professor Emeritus Dept. of Biochemistry & Molecular Genetics Office:321 CMWOffice:321 CMW Phone:6-5978Phone:6-5978 email: