Fundamentals of Nutrition

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					Lesson 1 Fundamentals of Nutrition
Mimi Giri, MD, Ph.D Department of Endocrinology, University Hospital of Ghent Ghent, Belgium

Carbohydrate Nutrition and Metabolism
• Introduction & Sources of carbohydrate in the diet

• Structures
• General functions of carbohydrate & Essentiality • Glucose from dietary carbohydrate:

digestion, absorption, transport into cells
• Glucose metabolism: glucose disposal & synthesis: • Glucose disposal: Glycolysis, TCA cycle, FFA synthesis, NEAA synthesis; Glycogen synthesis

• Glucose synthesis: purpose, glycogen breakdown and gluconeogenesis

• Introduction

Humans: ~ 50% of calories ingested as CHO (10 - 85%) 160 g starch, 120 g sucrose, 30 g lactose, 5 g glucose, 5 g fructose, trace maltose

• Introduction

Sources of carbohydrate: sucrose: “sugar” lactose: milk maltose: beer fructose: fruit, corn-syrup “processed foods” starch (amylose & amylopectin): wheat, rice, corn, barley, oats, legumes.... glycogen: muscle and liver

• Introduction

Glucose: ATP synthesis: all tissues
RBC, tissues of eye, renal medulla, brain, intestines, white blood cells, skin: rely primarily on glucose as energy source in the fed state

In the fed state, glucose is primarily obtained from dietary carbohydrate (CHO)

• Structures Monosaccharides:
Glucose, fructose, galactose

Dissacharides:
maltose: glucose + glucose lactose: glucose + galactose sucrose: glucose + fructose

Polysaccharides:
amylose: glucose + glucose +.... (linear) amylopectin: glucose + glucose +.... (branched) glycogen: glucose + glucose +...(very branched)

• General functions of carbohydrates

Energy: ATP synthesis (~ 4 kcal/g)
NEAA synthesis: carbon skeleton Fat synthesis: via acetyl-CoA Glycogen synthesis TCA cycle intermediates

Nucleotides: sugar portion
Glycoproteins Glycolipids

Overview of Metabolism
protein
ADP + Pi ATP

polysaccharides
ADP + Pi ATP

lipids
ADP + Pi ATP

amino acids

ADP + Pi ADP + Pi ATP ATP

hexoses pentoses
ADP + Pi
ATP

fatty acids
ADP + Pi ATP ADP + Pi ATP

pyruvate urea urea cycle

acetyl-CoA

O2

CO2

citric acid cycle

e-

electron transport chain oxidative phosphorylation

ATP

Overview of Catabolic Processes
Proteins Amino acids Carbohydrates Simple Sugars

Fats

Stage 1
Fatty acids

Glycolysis

Stage 2
Pyruvate Acetyl CoA Citric acid cycle ATP

Stage 3

Oxidative phosphorylation
ATP

Use of Amino Acids and Fatty Acids
Liver
glycogen

Fats and protein can also be used by the body as a source of energy. Not as easily used as carbohydrates.

glucose-6-P

Amino Acids

pyruvate

or
Fatty Acids

• Essentiality of carbohydrates

metabolic need is for glucose: ~300 g/d in humans
- glucose can be made from most AAs (not Leu) - glucose can be made from propionate (SCFA) - glucose can be made from glycerol - glucose cannot be made from fatty acids CHO not strictly essential in diet Relying solely on AAs etc. as precurser for glucose not prudent or practical (except for carnivores), so......

• Glucose from dietary carbohydrate: DIGESTION, ABSORPTION & TRANSPORT into cells Mouth salivary amylase: - hydrolyzes  1-4 bonds in starch - release: psychic (cephalic) stimuli mechanical stimuli: food in mouth chemical stimuli: food on taste buds - little digestion Stomach: Negligible

Stage One
• Hydrolysis of food into smaller sub-units.

Handled by the digestive system.

Stage One
• Salivary glands: • Secrete amylase. • - digests starch. • Stomach: • Secretes HCl. • - denatures protein and pepsin. • Pancreas: • Secretes proteolytic enzymes and lipases. • - degrades proteins and fats.

Stage One
• Liver and gallbladder: • Deliver bile salts. • - emulsify fat globules - easier to digest.

• Small intestine: • Further degradation. • Produces amino acids, hexose sugars, fatty acids and glycerol. • Moves materials into blood for transport to cells.

• CHO: Digestion, Absorption & Transport

Small Intestine

brush border

lumen

CHO Digestion: SMALL INTESTINE
LUMEN

lumen

CCK
pancreas

digesta

enzymes

CCK = cholecystekinin

Carbohydrate digestion: SMALL INTESTINE LUMEN
pancreas

lumen

enzymes

enzymes - -amylase

lumen (duodenum)

cuts 1-4 bond in starch:maltose, limit dex. efficient and fast acting enzyme

Carbohydrate digestion: SMALL INTESTINE Brush border enzymes occur on brush border
maltase: cuts maltose -limit dextrinase: cuts 1-6 bond lactase: cuts lactose sucrase: cuts sucrose result: monosaccharides glucose, galactose, fructose

• Carbohydrate: ABSORPTION

SITE OF ABSORPTION Jejunum & Ileum
GLUCOSE/GALACTOSE Absorbed by active transport - sugars move against concn gradient - requires ATP Facilitated diffusion of glucose - glucose concentration must be lower in enterocyte

• Carbohydrate: ABSORPTION

FRUCTOSE Carrier mediated facilitated diffusion - fructose conc must be lower in enterocyte
• CARBOHYDRATE TRANSPORT - enterocyte to portal vein to liver • GLUCOSE UPTAKE INTO CELLS - carrier mediated diffusion - stimulated by insulin (muscle, liver, adipocyte)

• Carbohydrate metabolism:

FRUCTOSE liver: fructose F-6-P

DHAP

glycolytic pathway

GALACTOSE liver: galactose gal-1-P

G-1-P

G-6-P glucose

• Glucose metabolism: glucose disposal & synthesis SIGNIFICANCE - Control blood glucose concentrations in starvation, exercise, stress, refeeding... 4 - 6 mmol/L (humans): 10 mM after meal high blood sugar: damage lens, kidney etc. complications of diabetes low blood glucose: brain damage & death - Control rate of glucose utilization in tissues

• Control rate of glucose utilization in tissues

e.g. How does liver assess how much glucose is being used by muscle or brain? e.g. When a high CHO meal eaten, rate of glucose absorption is high; to maintain normal blood glucose levels, the rate of glucose use in other tissues such as muscle must increase
Control & integration of glucose metabolism (disposal & synthesis) among tissues is required

Liver plays a major role!!

Diet Liver as Glucostat Gut

Glycerol

Liver

Amino Acids Lactic Acid

Fat

Blood Glucose 4.5-5.5 mmol/L

Muscle

Brain Kidney Urine BG >10mmol/L

Glands & other tissues

Factors affecting glucose concentration
Tend to raise • Hunger • Glucose absorption from gut • Hepatic glycogenolysis
– Adrenaline – Glucagon

• • • •

Tend to lower Satiety Glucose diffusion in ECF Muscular exercise Insulin
– – – –  Glucose oxidation  Glycogen deposition  Lipogenesis  Gluconeogenesis

• Gluconeogenesis in liver • Insulin antagonist
– Growth Hormone – Cortisol

{ glucosuria – in diabetes}

• Insulin destroying enzymes

• Fate of glucose

glycogen synthesis

ATP synthesis

GLUCOSE

NEAA synthesis

FFA synthesis

• Fate of glucose: glycolysis, TCA cycle & FFA synthesis
ATP synthesis

glucose ATP
pyruvate lactate FFA synthesis

acetyl-CoA

TCA cycle ATP lots!!

• Fate of glucose: glycolysis & TCA cycle purpose & tissues

glucose ATP
pyruvate

acetyl-CoA
TCA cycle

anaerobic glycolysis - RBCs, WBCs - kidney medulla lactate - enterocytes - lens, cornea - skin - (skeletal muscle)

FFA

- make ATP (2 ATP/glucose) - maintain blood glucose

• Fate of glucose: glycolysis & TCA cycle purpose & tissues

glucose ATP
pyruvate

acetyl-CoA
TCA cycle ATP

aerobic glycolysis - brain - liver - skeletal muscle - kidney cortex - etc. - make ATP (32 ATP/glucose) - maintain blood glucose

• Fate of glucose: glycolysis & TCA cycle stimulation and inhibition

glucose ATP
pyruvate

stimulation - high glucose - low ATP lactate - insulin inhibition - high ATP - FFAs

acetyl-CoA
TCA cycle ATP

FFA

• Fate of glucose: FFA synthesis tissues, stimulation (generally only occurs if excess calories eaten) glucose mainly:
liver adipocytes

pyruvate

diet
FFA TG ATP

acetyl-CoA
TCA cycle

stimulation - high glucose - high ATP * - insulin

• Fate of glucose: NEAA synthesis tissues, stimulation glucose pyruvate
mainly: liver muscles

diet
NEAA Proteins ATP

acetyl-CoA
TCA cycle

stimulation - high glucose - high ATP * - insulin

• Fate of glucose

glycogen synthesis

GLUCOSE

ATP synthesis glycolysis TCA cycle

NEAA synthesis

FFA synthesis

• Fate of glucose: glycogen synthesis

Liver & Muscle
glucose glycogen

glycogen
glucose gluc

glycogen

glucose

glucose

SI

Liver

skeletal muscle

• Fate of glucose: glycogen synthesis Liver & Muscle glucose glycogen stimulation: high glucose (liver) insulin low glycogen (muscle)
glycogen
glucose gluc + ins glycogen

glucose

+ ins

glucose

SI

Liver
pancreas

insulin (ins)

skeletal muscle

• Fate of glucose

glycogen synthesis
GLUCOSE

ATP synthesis

NEAA synthesis

FFA synthesis

glucose utilization result: decrease blood glucose level regulate tissue glucose use

• Glucose synthesis:

glycogen breakdown
GLUCOSE

gluconeogenesis

glucose synthesis purpose: - maintain blood glucose level: fasting, sustained exercise, stress, hypoglycaemia - regulation of tissue glucose use tissues: liver, muscle, kidney

• Glucose synthesis: glycogen breakdown (LIVER)

glycogen
stimulation:

glucose immediate glucose source

low blood glucose adrenalin/glucagon inhibition:insulin

glycogen
+ glucagon

CO2 glucose glucose

glucose

tissues
SI

Liver
pancreas

glucagon

• Glucose synthesis: glycogen breakdown (muscle)

glycogen
stimulation:

G-6-P (muscle) local use only
adrenalin (exercise/stress)
note: glycogen G-6-P

glycogen + adr G-6-P

CO2 lactate
glucose

skeletal muscle

• Glucose metabolism: disposal & synthesis
Liver: major role in regulation of blood glucose

high blood glucose: glucose uptake

glucose

glycogen CO2 FFA +i +i +i glucose

+i

glucose

SI

Liver

+ i = stimulated by insulin

• Glucose metabolism: disposal & synthesis
Liver: major role in regulation of blood glucose

low blood glucose: glucose release
alanine lactate

glycogen ala lactate

+g
glucose
glucose

SI

Liver

+ g = stimulated by glucagon

• Physiological importance of gluconeogenesis

low CHO diet, early starvation (no CHO intake),
infection & trauma (high glucose need)
gluconeogenesis

glycogen

glucose

glucose

brain & anaerobic tissues

SI

Liver

• Regulation of glucose use among tissues and role of fatty acids e.g. fed state/high CHO diet glucose uptake and use
glycogen ATP

+ ins
glucose gluc

+ ins

glucose

SI

Liver
pancreas

insulin (ins)

• Regulation of glucose use fed state/high CHO diet glucose uptake and use

glyc glucose

ATP

+ins
gluc

CO2/ATP

glucose

+ins

?
gluc

skeletal muscle SI

Liver
pancreas

insulin (ins)

• Regulation of glucose use

fed state/high CHO diet role of fatty acids

TG - ins FFA

adipocyte

FFA glyc ATP glucose gluc

CO2/ATP

glucose

+ ins

gluc

skeletal muscle SI

Liver
pancreas

insulin (ins)

• CHO metabolism:Vitamin & Mineral Co-factors

biotin (carboxylation) Thiamine: Vit B1 Riboflavin: Vit B2 (FAD) Niacin: Vit B3 (NAD) pantothenic acid (Acetly-CoA)

glucose
biotin B3 B3 B3

pyruvate

lactate

B1,B2,B3,Mg2+ pantothenic acid

acetyl-CoA
TCA cycle
B1, B3

Diabetes Mellitus: Metabolism out of control
• Introduction • Symptoms and clinical features • Metabolic effects of insulin on CHO metabolism • Metabolic effects on protein & fat metabolism • Lack of insulin (diabetes mellitus) - effect on glucose uptake, utilization & production - effect glucose production - effect on protein synthesis & protein breakdown - effect on TG breakdown (fat cells) - effect on ketone body synthesis (liver)

• Introduction Diabetes Mellitus or Type 1 (previously juvenile onset) or insulin-dependent diabetes mellitus (IDDM) recognized as a disease for 2000 years -cells of Islets of Langerhans (pancreas) damage: inadequate insulin production Diabetes illustrates problems that arise when integration of metabolism is impaired: carbohydrate, protein & lipid metabolism

•Symptoms and clinical features

polyuria polydipsia polyphagia weight loss dehydration glycosuria ketosis/ketoacidosis unconsciousness/coma

•Metabolic effects of insulin on CHO metabolism glucose uptake and use decrease blood glucose
AAs, lactate glyco

-ins glucose +ins

+ins
glucose glucose +ins

CO2/ATP
gluc

skeletal muscle SI

Liver

insulin = ins

•Metabolic effects of insulin on protein metabolism - stimulate amino acid uptake - stimulate protein synthesis - inhibit protein degradation
protein

protein

+ins
AAs AAs

+ins Amino +ins Acids

+ins

-ins

amino acids

SI

Liver

skeletal muscle
insulin = ins

•Metabolic effects of insulin on lipid metabolism - stimulate triglyceride (TG) synthesis - inhibit triglyceride breakdown - inhibit ketone body synthesis

ketone bodies

-ins
AAs FFAs

free fatty acids

TG +ins -ins FFA adipocyte
insulin = ins

SI

Liver

•Lack of insulin (diabetes mellitus)
- effect on glucose uptake, utilization & production - effect on protein synthesis & protein breakdown

- effect on TG breakdown (fat cells)
- effect on ketone body synthesis (liver)

•Lack of insulin (diabetes mellitus): effect on glucose uptake, utilization & production decreased glucose uptake and use increased glucose production increased blood glucose
AAs AAs, lactate gluc glucose fat

glucose
>10 mM glucose - glucosuria - polyuria - polydipsia - dehydration - coma

SI

Liver

skeletal muscle

•Lack of insulin (diabetes mellitus): effect on protein synthesis & protein breakdown decreased protein synthesis increased protein breakdown protein wasting

AAs gluc glucose protein fat AAs Amino Acids

protein

amino acids

SI

Liver

skeletal muscle

•Lack of insulin (diabetes mellitus): effect on TG breakdown & ketone body synthesis increased TG breakdown weight loss increased ketone body synthesis metabolic acidosis
ketones AAs gluc fat FFA Ketones

TG FFA adipocyte

FFA

SI

Liver

•Lack of insulin (diabetes mellitus): SUMMARY
FFA
FFA AAs gluc glucose fat AAs KBs

TG
adipocyte

FFA
Ketones protein

glucose
Amino Acids amino acids

SI

Liver

skeletal muscle

•Lack of insulin (diabetes mellitus): Summary
The normal flow of substrates following food intake is largely dependent on the secretion of insulin. Insulin exerts a potent, positive effect on anabolism, while inhibiting catabolic pathways. Diabetes is a vivid negative example that emphasizes the integration of metabolism and the importance of metabolic regulation to continuance of life. from Advanced Nutrition & Human Metabolism Groff & Gropper 2000

. Fibre
• Introduction, Definition & Sources • Type of fibre and properties - cellulose, hemicelluloses, -glucans, pectins, lignin - soluble vs. insoluble fibre • Physiological & Metabolic effects - water holding capacity, binding of nutrients, fermentability • Significance • Recommended intakes

• Introduction In humans, pre-1970’s fibre believed to have no nutritional value & antinutrient Since 1970’s, fibre: - energy value - gastrointestinal function - nutrient availability - prevention & treatment of many diseases

• Definition

- fibre is not a single entity - difficult to define “Endogenous components of plant material in the diet that are resistant to digestion by enzymes produced by man. They are predominantly non-starch polysaccharides and lignin and may include, in addition, associated substances.” (Health and Welfare Canada)

• Sources

Plant material plant cell wall : 95% of fibre cementing material in plants legumes: beans, peas forages: alphalpha, timothy hay.... bran of cereals: wheat, oats, corn, rice.... skin of fruits & vegetables

• Type of fibre & properties Cellulose - structural component of cell walls - linear polymer of -D-glucose - forages, bran of grains - high degree of crystallinity fibrous & water insoluble - monogastric animals lack cellulase in SI cannot hydrolyze -1,4 linkage so indigestible colon: bacteria thus partly fermented

• Type of fibre & properties

Hemicelluloses - polymers of: mannose, galactose, glucuronic acid, xylose, arabinose (5 & 6 carbon sugars) with some branching - forages, bran of cereals, legumes - not very water soluble (depends on type) - monogastric animals: hemicelluloses are not digested in SI partly digested in colon by bacteria

• Type of fibre & properties -glucans (gum) - cell walls of grasses - bran coat of barley, oats - glucose polymer: -1,4 and -1,3 (branched) - water soluble - monogastric animals: not digested in SI gummy and viscous large intestine: rapidly fermented

• Type of fibre & properties Pectins - structural component of plant cell walls cementing material - polymers of polygalacturonic acid, which may or may not have a methylester group - fruit (skin), forages (alfalfa), rye, - soluble in H2O & form gels (branched) - monogastric animals: pectins are not digested in SI digested rapidly colon by bacteria

• Type of fibre & properties Lignin - NOT a carbohydrate - structural component of plant cell walls - aromatic polymer; polyphenolic (hydrophobic) - insoluble in water - not digestible in SI or by bacteria

Mucilages & algal polysaccharides - carragenan, agar - water soluble - highly fermentable

• Type of fibre & properties Dietary Fibre

Soluble
some hemicelluloses -glucans pectins gums, mucilages

Insoluble
some hemicelluloses cellulose lignin

- solubility affects water-holding capacity, fermentability, nutrient adsorption - these exert physiological & metabolic effects

• Physiological & Metabolic effects

water-holding capacity ability to hold water
faecal bulk colonic transit time (faster) reduce constipation

viscous & gel-forming mixing of digestive enzymes with food nutrient diffusion rate slower rate of absorption
SI transit time (slow passage) soluble fibre increase satiety

• Physiological & Metabolic effects Adsorption or binding of nutrients by fibre - lignin, pectin, -glucan can bind some nutrients bind and reduce absorption of bile acids cholesterol used for more bile acid synthesis lower serum cholesterol reduce Ca2+, Fe2+, Zn2+ absorption COO- bind divalent cations pectins, hemicellulose

• Physiological & Metabolic effects Fermentability - depends on fibre (esp. solubility) - residence time - bacteria population Short chain fatty acids (SCFAs) are made acetate propionate butyrate Gases: H2, CO2, methane

• Physiological & Metabolic effects Short chain fatty acids - absorbed
acetate (2 C) acetyl-CoA ATP or FFAs

propionate (3 C)

liver

glucose

butyrate (4 C) used as fuel for intestinal cells

Fibre that is fermented in can be a source of energy and glucose

• Significance Fibre is not inert Energy (< 4 kcal/g but > 0 kcal/g) Disease prevention & treatment constipation/haemorroids/appendicitis heart disease/plasma cholesterol adult-onset diabetes/glucose absorption obesity/satiety Mineral deficiency rare: intake low and fibre/phytate high

References
• Groff and Gropper, 2000. Advanced Nutrition and Human Metabolism