Lecture 3 Carbs and Lipids

What are the accessory organs?

Salivary gland's, liver, gallbladder, pancreas

What are the organs of the gastrointestinal tract?

Oral cavity, pharynx, esophagus, stomach, small intestine, large intestine

Salivary gland's

Release a mixture of water mucus and enzymes

Liver

Produces bile, and important secretion needed for lipid digestion

Gallbladder

Stores and releases bile, needed for a lipid digestion

Pancreas

Releases pancreatic juice that neutralizes chyme and contains enzymes needed for carbohydrates, proteins, and lipid digestion

Oral cavity

Mechanical breakdown, moist evening, and mixing of food with saliva

Pharynx

Propels food from the back of the oral cavity into the esophagus

Esophagus

transports food from the pharynx to the stomach

Stomach

Muscular contractions mix food with acid and enzymes, causing the chemical and physical breakdown of food into chyme

Small intestine

Major site of enzymatic digestion and nutrient absorption

Large intestine

Receives and prepares undigested food to be eliminated from the body as feces

glycosidic bond

Digestion involves enzymatic cleavage of the oxygen bridge called

Polysaccharides

Salivary Alpha-amylase -mouthPancreatic Alpha-amylase- small intestineResistant starchesLess salivary and pancreatic Amylase in infantsAmylase attacks only straight chain region

Amylose

The linear poly glucose chain occurs in

Amylopectin and glycogen

The branched chain polymer occurs in

digestion of amylose

Salivary gland releases salivary alpha-amylase, which hydrolyzes a-1,4 glycosidic bonds in amylose, forming dextrins

digestion of amylopectin

Salivary gland to release salivary alpha-amylase, which hydrolyzes a-1,4 glycosidic bonds in amylopectin, forming dextrins

Maltose + maltotriose

Amylose

Maltose + maltotriose + limit dextrins

Amylopectin, glycogen

2 exoglucosidases

Each carries two domains and have two activities-maltase-glucoamylase and sucrase-isomaltase

Disaccharides are

active in micro villi of enterocytes (brush orer cells)

Intestinal walls

fold into villi that are lined with absorptive mucosal cells containing microvilli

Absorption of glucose & galactose - Into cell:

active transport (symport)- specific receptor SGLT1

Absorption of glucose & galactose - Into blood:

diffusion, GLUT2

Absorption of fructose - Into cell:

facilitated transport - GLUT5

Absorption of fructose - Into blood:

GLUT2

Absorption of fructose

Slower than glucose and galactose

SGLT1 (encoded by SLC5A1 gene)

• Co-transports 2 sodium ions and one aldohexose • Km for glucose/galactose is 0.5mM and 5mM for sodium. High glucose flux even at low luminal glucose concentrations.

GLUT5 (encoded by SLC2A5 gene)

• Facilitated transport of fructose • Low affinity, 5-6mM Km

GLUT5 expression

is induced by presence of fructose in lumen

SGLT1 is

expressed at high levels during infancy, GLUT5 is low

Hexose transporter

expression increases during enterocyte differentiation and migration up the villi.

•mRNA of transporters (GLUT2, GLUT5, SGLT1)

shows diurnal variation with increase just before feeding

Activation of sweet taste receptors or SGLT1 transport activity in enteroendocrine cells

may lead to increased expression of hexose transporter genes

Factors affecting carbohydrates absorption

- Effect of physical state of starch (processing, retrograde) - Effect of transit time (fat, fiber, high osmolality) - intestinal or pancreatic disease; High AMY1 copy number - single mutation can produce defective SGLT1

Disaccharidase activity may be lost/reduced:

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gastric bypass surgery

• Bypasses 90% of the stomach, the entire duodenum, and proximal jejunum • Ileum may adapt through cellular proliferation

Use of Antidiabetic drugs

• Development of inhibitors of starch digestion to treat diabetes and obesity to control blood sugar • Acarbose, a pseudotetrasaccharide, amylase inhibitor, sucrase and maltase inhibitor; Unpleasant side effects due to undigested starch • Miglitol and Vogliobose inhibit disaccharidase activity; associated with symptoms of carbohydrate malabsorption • Newer molecules - salacinol and kotalanol (salacia reticulata herb) more effective as inhibitors

Regulation of Postprandial Glycemia

• Carbohydrates are absorbed à plasma glucose levels rise à insulin is secreted • Carbohydrate intake is accompanied by secretion of incretin hormones by gut EECs • Incretin hormones have effects on satiety, gastric emptying, endogenous glucose production and glucose utlilization. • Incretins affect insulin secretion even before plasma glucose level increases; 30 to 60% of increase in plasma insulin following an oral glucose load • Glucose-dependent insulinotropic polypeptide (GIP) - 42 amino acid peptide is secreted enteroendocrine K cells in upper small intestine • Glucagon-like peptide -1 (GLP-1) - 30 amino acid peptide is a proteolytic cleavage product of proglucagon and is secreted by enteroendocrine L cells of lower small intestine (ileum) and colon

Secretion of Incretins

GIP and GLP-1 are secreted in response to macronutrient ingestion. • Glucose in gut is most important for incretin release à through activation of SGLT1 in EECs • Involves the co-transport of sodium ions by SGLT1 à depolarizes the plasma membrane à opening of voltage-sensitive calcium channels à exocytosis of incretin-containing vesicles • GIP and GLP-1 bind to their G protein coupled receptors on pancreatic beta cells to initiate signaling (adenylate cyclase and cAMP) that culminates in the secretion of insulin by endocrine pancreas • Effects of incretins on insulin secretion are glucose dependent (higher in hyperglycemia)

Effects of Incretins

• GIP and GLP-1 promote insulin biosynthesis • Promote the survival and proliferation of pancreatic beta cells. • GLP-1 suppresses glucagon secretion in a glucose-dependent manner (Glucoregulatory role) • Plasma glucose homeostasis through other mechanisms: • Paracrine activation of EEC and enterocyte receptors • Neurocrine activation of receptors on vagal afferent terminals and receptors on enteric neurons to modulate intestinal function and in other tissues • GLP-1 regulates gastrointestinal motility by inhibiting gastric emptying during the postprandial phase

glycemic response

- Degree and duration to which blood glucose level is elevated after consuming a portion of food that would provide 50g of digestible carbohydrates and measured [AUC] for the next 2 hours after a meal

glycemic index

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Glycemic load

Amount of food used to determine glycemic index is not the amount typically consumed Glycemic load is the glycemic index normalized to serving standards - GI x g of CHO in 1 serving of foodand then divided by 100 - Global indicator of glucose response and insulin demand • Higher postprandial glycemia and hyperinsulinemia are universal mechanisms for chronic disease progression

dietary fiber

nondigestible CHO & lignin that are intact & intrinsic in plants

Functional fiber

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How do dietary fiber and functional fiber differ

- types of sugar residues - arrangement of residues (branching and substitution) - secondary structure (e.g. resistant starch); packing or arrangement can restrict enzyme access

definition of dietary fiber

Codex Alimentarius Commission definition (2010): "Carbohydrate polymers with 10 or more monomeric units that are not hydrolyzed by the endogenous enzymes in the small intestine of humans and belong to the following categories: 1. Edible carbohydrate polymers naturally occurring in the food as consumed; 2. Carbohydrate polymers, which have been obtained from food raw material by physical, enzymatic, or chemical means and which have been shown to have a physiological effect or benefit to health as demonstrated by generally accepted scientific evidence to competent authorities; and 3. Synthetic carbohydrate polymers which have been shown to have a physiological effect or benefit to health as demonstrated by generally accepted scientific evidence to competent authorities.

Cellulose

• Dietary & functional fiber • Long, linear polymer of b 1-4 linked glucose units; microfibrils • Plant cell walls; major component of dietary fiber • Sources: bran, legumes, nuts, peas, root vegetables, cabbage family, outer covering of seeds, apples • Hemicelluloses not related to cellulose; similarity in solubility properties

Pectins

• Dietary & functional fiber • Backbone = galacturonic acid • Cell wall & middle lamella in plants • Water-soluble, gel-forming • Sources: apples, strawberries, citrus

Lignin

• Main non-carbohydrate component of dietary fiber; Polyphenolic units • Structural components of plants - found in stems, seeds, bran layer

Gums

• Hydrocolloids • Site of injury • High water solubility; form viscous solutions • Mucilages protect seeds from drying (Psyllium is mucilage from husk of pysillium seeds)

Resistant Starch

• Starch that cannot be digested by humans • Arrangement of starch molecules • Types - RS1 - Physically inaccessible (but digestible) resistant starch that can be found in seeds, legumes, or unprocessed grains - RS2 - Naturally occurring semi-crystalline granules that are present in foods such as uncooked potatoes and green bananas - RS3 - From cooking & cooling or extruding foods (legumes, cooked or chilled potatoes and cornflakes and retrogradation) - RS4 - Specially processed starches that yield chemically modified starch • RS1 & RS2 = dietary fibers, RS3 & RS4 = functional fibers

Fructans--(Inulin, Oligofructose, & Fructooligosaccharides)

• Edible plant cell components • Fructose units in chains of varying length ( at least 1 fructosylfructose); linear or branched • Resistant to hydrolysis and absorption • Prebiotics • Sources: chiccory, asparagus, onions, garlic, artichokes, tomatoes, bananas

Intestinal Bacteria (Microflora), Pre- and Probiotics, and Disease

• Human gut - 100 trillion microbial organisms • Fermentation - breakdown of CHO & protein anaerobically • Lactate & short-chain fatty acids, gases • Probiotics - foods containing live bacterial cultures • Prebiotics - food ingredients that promote the growth of specific beneficial gut bacteria. • Synbiotics - combinations of both pre- and pro-biotics. • Benefits: - Reduction of diarrhea incidence -Improvements in gut health - Elimination of allergies -Prevention of infections

Selected Properties & Physiological Effects of Fiber

Paleolithic diet - 100g fiber (more fruits and vegetables) Current western diet - 15g fiber (more cereal fibers) • Important properties include: - Soluble fibers form more viscous solutions and are more fermentable than insoluble fibers - Water-soluble: some hemicelluloses, pectin, gums, b-glucans, mucilages, algal polysaccharides - Water-insoluble: cellulose, lignin, some hemicelluloses, chitosan, chitin

What factors influence fermentation rate?

*Chemical and Physical Structure -Methyl esters in pectin -Esterification of starch -Fermentation rate likely a function of links between sugars -Purification can increase fermentation and SCFA -Type and amount of crystallinity -Particle size*Processing -Extrusion cooking can change the fermentation pattern -Enzymatic treatment -Chemical treatment (alkali, hydrogen peroxide) *Combinations of fibers -both soluble and insoluble fibers -soluble fiber consumed with starch increase viscosity resulting in reduced rate of digestion

Physiological effects of Dietary Fiber in the Stomach and the Small Intestine

• Dietary fiber can delay the rate at which food enters the small intestine. - Chewing of bulky foods - Slowing of gastric filling and emptying (viscosity of chyme) • High fiber foods can promote satiety - Feeling of fullness produced by distention of the stomach (through neurological mechanisms and physical bulkiness of the fiber) - Release of satiety release hormones - Viscous fibers are more satiating; Whole foods

Physiological effects of Dietary Fiber in the Stomach and the Small Intestine (part 2)

• Dietary fiber slows the rate of nutrient absorption, lowers postprandial glucose levels and limits cholesterol absorption. - Slow gastric emptying; entrapment in gel-like matrix; interference with micelle formation; dilution of enzymes and digestible components; decreased enzyme access; impeding of mixing à slower movement - Slowing of macronutrient absorption

Dietary Fiber and Health

• Cardiovascular Disease - Lower blood pressure, improve serum lipids, and inflammation • Obesity Prevention • Type 2 Diabetes • Bowel Health - Mostly constipation and not other gastrointestinal disorders • Microbiota

Regulation of Macronutrient Metabolism at Tissue-level

• Tissues differ in structure and function (e.g. Muscle and adipose and GLUT4) • Tissues differ in their capacities to use different types of fuel. • Most tissues will be able to use glucose (postprandial) or fatty acids (starvation). Some tissues lack the ability to make this switch (RBC no mitochondria) • The liver plays a key role in modulating the mixture of circulating fuels that are supplied to the rest of the body. (e.g. Fed state; post-absorptive state; starved state) • Tissue-specific gene expression determines the structure and metabolic capacities of various tissues. • Overall expression of enzymes may differ; Differential expression or isoforms in different cells. (e.g. glycogen breakdown in muscle and liver differ in phosphorylase regulation and end product)

adipose tissue

• insulin dependent • complete oxidation • partial degradation to glycerol (for TG) • metabolized to acetyl CoA for fatty acid synthesis and storage

brain tissue

• insulin independent • complete oxidation

RBC in tissues

• insulin independent • partial oxidation to lactate

liver tissue

• insulin-independent • complete oxidation • glycogen storage • carbons for biosynthesis of other compounds • release glucose from glycogen • synthesize glucose • into other pathways

Skeletal muscle and heart

• insulin-dependent • complete oxidation • glycogen storage • Heart is aerobically metabolic all the time • Skeletal muscle has periods of high and low activity; limited anerobic capacity