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Lipids Triglycerides can be classified by their chain length, their shape and which of the following?

A Their carboxyl group

B Their weight

C Their methyl group

D Their level of saturation Which of the following is usually solid at room temperature?

A essential fatty acids

B saturated fatty acids (SFAs)

C monounsaturated fatty acids (MUFAs)

D polyunsaturated fatty acids (PUFAs) Which of the following describes fatty acids with a double bond at one part of the molecule?

A Monounsaturated

B Hydrogenated

C Saturated

D Polyunsaturated Which of the following foods are rich sources of saturated fatty acids?

A walnuts and cashew nuts

B olive and canola oils

C cotton seed and safflower oils

D butter and lard

Which of the following statements is true about trans fats? They are a result of the hydrogenation process Why do food manufacturers hydrogenate fats?

A Because trans fats decrease the risk of cardiovascular disease.

B To keep fats in foods from going rancid, thus increasing shelf life.

C To improve the texture and taste of food.

D All of the above.

Food-Based Lipids

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Three types of lipids are found in foods and in body cells and tissues: • Triglycerides • 95% of fat we eat is in this form • Most body fat also stored as triglycerides • Phospholipids • Soluble in water • Help with digestion of dietary fat • Sterols • They occur naturally in plants, animals, and fungi, and can be also produced by some. • The most familiar type of animal sterol is cholesterol, which is vital to cell membrane structure, and functions as a precursor to fat-soluble vitamins and steroid hormones.

Food-Based Lipids

Know relativities Essential Fatty Acids (EFA)

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Some triglycerides contain essential fatty acids • Essential fatty acids: cannot be made by the body and must be obtained from food • Body cannot insert double bonds before the ninth carbon from the Omegacarbon • Linoleic acid (omega-6 fatty acid) • Found in vegetable and nut oils • metabolized to arachidonic acid (precursor to eicosanoids)

Essential Fatty Acids (EFA)

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Alpha-linolenic acid (omega-3 fatty acid): • Found in vegetables, soy, flaxseeds, and walnuts • Two Omega-3 fatty acids found in fish and fish oil are Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) • Reduce risk of heart disease • Stimulate prostaglandins and thromboxanes that reduce inflammatory responses • Reduce blood clotting and plasma triglycerides

Lipid Digestion

Pancreatic enzymes  2FAs and monoglyceride Cholesterol esterase  break ester bond between cholesterol and FAs Phospholipase phospholipids into smaller parts

Lipid Digestion

Fat Absorption

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A micelle is a spherical compound made up of bile salts and phospholipids Micelles capture fatty acids, cholesterol and monoglycerides and transport them to enterocytes for absorption Within the enterocytes, fatty acids and monoglycerides are reformulated back into triglycerides and packaged into lipoproteins

Fat Absorption

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Lipoprotein transports lipids for absorption

Fat Absorption

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Chylomicron: lipoprotein produced in intestine to transport lipids from a meal • Composed of fatty acids surrounded by phospholipids and proteins • Soluble in water • Absorbed by cells of the small intestine • Travel through the lymphatic system • Transferred to the bloodstream

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Fat Absorption

Fat Is Stored in Adipose Tissues

Short- and medium (14C or less)-chain fatty acids are absorbed more quickly since they are not arranged into chylomicrons

Reassembly of lipid components into a chylomicron

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Triglycerides in the chylomicrons must be disassembled by lipoprotein lipase before they can enter body cells In body cells, triglycerides can be: • Used immediately for energy • Used to make lipid-containing compounds • Stored in muscle and adipose tissues

Importance of Lipids In The Body

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Lipids perform numerous functions in our body Lipids provide energy and help perform essential physiological functions Lipids are major fuel source when we are at rest • provide 9 kcal of energy per gram • help perform essential physiological functions • 30% to 70% of energy used at rest by muscles and organs come from lipids

Importance of Lipids In The Body

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Lipids fuel physical activity • During aerobic exercise, lipids can be mobilized from muscle tissues, adipose tissues or blood lipoproteins • Adrenaline - activates hormone sensitive lipase  stimulates fat breakdown • Adrenaline also signals pancreas to decrease insulin production  stimulates fat breakdown Fat storage for later use • While fasting, sleeping or exercising body has access to stored fats • Glycogen storage can only last for 1-2 days therefore, fat storage is essential to protect health

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Importance of Lipids In The Body

Components of Important Biological Compounds • Constituent of cell membranes • Prevent DNA damage • Fight infection • Involved in fetal growth and development (brain and visual centers) • Transport of Fat-Soluble Vitamins

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Importance of Lipids In The Body

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How Much Dietary Fat Should We Eat?

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Don’t Let the Fats Fool You

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Dietary fat enables the absorption and transport of fat soluble vitamins A, D, E, and K Fat soluble vitamins are absorbed as a part of micelles and transported as a part of chylomicrons

Maintenance of Cell Function and Protection to the Body • PUFA and phospholipids - maintain membrane integrity • Maintain cell fluidity and flexibility • Facilitate cell communication (brain and spinal cord) • Protect organs • Insulation Flavor and Texture of Foods • Fats provide flavor and texture to food Fats make us feel satiated • Fats are energy dense Acceptable Macronutrient Distribution Range (AMDR) for fat: 20−35% of calories • Minimize saturated and trans fatty acid intake to lower risk of heart disease • Active people may need more energy from carbohydrates and can reduce their fat intake to 20−25% of total calories DRIs for essential fatty acids: • Linoleic acid: AMDR of 5−10% of energy • Alpha-linolenic acid: 0.6−1.2% of energy • 5:1 to 10:1 ratio of linolenic:alpha-linolenic acid Saturated fat: less than 10% of energy • Trans fats: reduced to the absolute minimum Visible fats • Fats we add to foods Invisible fats • Fats hidden within foods - Occur naturally or added during processing Beneficial fats • Omega-3 fatty acids may be low in Canadian diet • Sources: Fish, walnuts, soy, canola, flaxseed Switch to more healthy fats without increasing total fat intake: • Use olive or canola oil in place of butter or margarine • Select low-fat or nonfat dairy products

Don’t Let the Fats Fool You

Don’t Let the Fats Fool You

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Fat replacers • Used to lower fat content of foods • Found in chips, cakes, cookies • May cause GI side effects in large amounts • Example: Olestra (Olean) • Also protein-based replacers such as Whey protein and Simplesse • Improves total nutrient profile and decreases kilocal content

Role Of Lipids in Cardiovascular Disease

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Cardiovascular disease • Can result in heart attack or stroke • Heart diseases are the second and stroke is the third leading cause of death in Canada Risk factors for cardiovascular disease: • Being overweight • Physical inactivity • Smoking • High blood pressure • Diabetes mellitus • Inflammation

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Cardiovascular Disease

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Role of Dietary Fats • Highly saturated and trans fat intakes increase blood cholesterol • Omega-3 fatty acids reduce inflammation and blood triglycerides • Dietary fats increase blood lipids which include: • Chylomicrons • Very-Low-Density Lipoproteins (VLDLs) • Low-Density Lipoproteins (LDLs) • High-Density Lipoproteins (HDLs)

The chemical components of various lipoproteins

Cardiovascular Disease

Diets high in saturated fats: •

Decrease the removal of LDLs

Cardiovascular Disease

Cardiovascular Disease

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Total serum cholesterol: • Consuming dietary cholesterol does not decrease the amount of cholesterol synthesized in the body but increases the total serum cholesterol level • Both dietary cholesterol and saturated fats are found in animal foods • Selecting low-fat meat, poultry, and dairy products and consuming egg whites only can reduce the amount of dietary cholesterol

Cardiovascular Disease

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Diets high in trans fatty acids: • Can raise blood levels of LDL-cholesterol as much as saturated fat • Are abundant in hydrogenated vegetable oils (margarine, baked goods, fried foods) Health Canada requires that trans fatty acid content be listed on labels for conventional foods and some dietary supplements

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Cardiovascular Disease

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Lifestyle changes can prevent or reduce cardiovascular heart disease • Total fat intake: 20−35% total calories • Saturated fat: less than 7% total calories, Cholesterol: less than 300 mg per day and Trans fat: reduce to absolute minimum • Increase omega-3 fatty acids • Increase dietary fiber: 20−30 grams per day • Maintain blood glucose and insulin concentrations • Eat smaller meals throughout the day • Consume no more than 2 alcoholic drinks/d for men and 1 drink/day for women • Maintain active lifestyle • Balance calorie intake and physical activity • Decrease salt intake - DASH diet (Dietary Approaches to Stop Hypertension)

Cardiovascular Disease

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Medicines help reduce risk • Endogenous cholesterol synthesis inhibitors: statins • Block and enzyme in cholesterol synthesis • Lower blood LDLs and VLDLs • Bile acid sequestrants • Bind bile acids, preventing reabsorption by intestines • Liver must use already made cholesterol

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Lecture 7 Metabolism How Is Energy Extracted from Carbohydrates?

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Nicotinic acid (in the form of niacin) • Not the form found in multivitamins • Many side effects

When glucose is transported to the liver, it is: • Phosphorylated and metabolized for energy or stored as glycogen in the liver • Released into circulation for other cells to use as fuel or stored as glycogen (muscle tissue) • Converted to fatty acids, if glucose exceeds energy needs, and stored as triglycerides in adipose tissue Fructose and galactose are converted to glucose in the liver and follow the same process Oxidation of glucose involves glycolysis, TCA cycle and oxidative phosphorylation

Glycolysis

In the Absence of Oxygen

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Pyruvate is converted to lactic acid in absence of oxygen NADH is oxidized to NAD+ With the conversion of one molecule of glucose into lactic acid, the number of ATP produced is two

Pyruvate is Converted to Acetyl CoA

Metabolic Crossroads

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Tricarboxylic Acid Cycle

Oxidative

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Pyruvate is converted to acetyl CoA in the presence of oxygen in mitochondria One CO2 is released during the reaction

Acetyl CoA is not only generated from glucose oxidation Fatty acid and amino acid catabolism also generates acetyl CoA

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The TCA cycle is a continuous circle of eight metabolic reactions Occurs in mitochondria

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Occurs in the electron transport chain

Phosphorylation

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How Is Energy Extracted from Fats?

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-oxidation of Fatty Acids

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Takes place in the inner membrane of mitochondria Enzyme-driven reactions called the electron carriers accept and then donate electrons Source of energy rich electrons: NADH and FADH2 Oxygen is the final acceptor of electrons

Lipolysis: dietary and adipose triglycerides are broken down by lipases to yield glycerol and three free fatty acids • Triglycerides in lipoproteins broken down by lipoprotein lipase • Triglycerides in adipose cells broken down by hormone sensitive lipase Glycerol is converted to pyruvate, then to acetyl CoA for entry into the TCA cycle Fatty acids are converted to acetyl CoA, which is used for energy

Attached to albumin, fatty acids are transported to working cells in need of energy (muscle or liver cells)

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Fatty acids must be activated by Coenzyme A before being shuttled across the mitochondrial membrane by carnitine Long-chain fatty acids are broken down into two-carbon segments to form acetyl CoA

Extraction of Energy from Triglycerides

Fatty Acids Cannot Form Glucose

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There is no metabolic pathway to convert acetyl CoA into pyruvate for glucose synthesis • Cells cannot convert acetyl CoA to glucose so fatty acids don’t feed into glucose production

Ketone Synthesis

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Fat catabolism increases in case of • very low carbohydrate diet • Prolong fasting • too little insulin to allow glucose to enter cells Oxaloacetate level and thus TCA cycle activity decreases Acetyl CoA builds up, exceeding the ability of the TCA cycle to metabolize it. Production of ketone bodies in the liver increases dramatically that inappropriately lowers the blood pH (Ketosis) Ketoacidosis occurs when blood pH falls, further resulting in severe dehydration Ketone synthesis provides a backup energy system for carbohydrate-deprived cells

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Ketone Synthesis

How Is Energy Extracted from Proteins?

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The body preferentially uses fat and carbohydrate as fuel sources Protein is saved for metabolic functions that cannot be performed by other compounds Protein is used for fuel primarily when total energy or carbohydrate intake is very low

Proteins are Broken Down to Amino Acids

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Proteolysis: dietary proteins are digested into amino acids or small peptides Amino acids are transported to the liver • Made into proteins • Released into the blood for uptake by other cells for building and repair functions Excess dietary protein • Used for energy or stored as triglycerides

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Proteins are Broken Down to Amino Acids

Proteins are Broken Down to

Deamination • • • •

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During starvation, the body turns to its own tissues for energy Utilization of amino acid begins with the removal of amine group End products of deamination is ammonia and keto acid (carbon skeleton) Carbon skeleton is channeled into glycolysis or the TCA pathway to produce energy

Carbon skeleton from amino acid deamination

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Amino Acids

Glucogenic amino acids • converted to pyruvate • Alanine, glycine, serine, cysteine, and tryptophan • Ketogenic amino acids • converted to acetyl CoA • Leucine and lysine • Both glucogenic and ketogenic amino acids • Tyrosine, phenylalanine, tryptophan, lysine, and leucine

Energy From Protein

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Ammonia from amino acid deamination • Used as nitrogen source for synthesis of nonessential amino acids • High levels are toxic • Liver converts ammonia to less toxic urea

How Is Alcohol Metabolized?

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Alcohol is oxidized primarily in the liver by enzymes: • Alcohol dehydrogenase (ADH) • Aldehyde dehydrogenase (ALDH) • Microsomal ethanol oxidizing system (MEOS)

Alcohol Oxidation

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First-pass metabolism: small amount of alcohol is oxidized in the stomach, before being absorbed into the bloodstream Gastric ADH activity • Reduces alcohol absorption • Genetic, age, and gender differences in amount of activity

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Most is absorbed into the blood and transported to be oxidized by the liver Liver typically oxidizes alcohol at a constant rate (about 1 drink/h) This rate varies with the individual’s genetic profile, state of health, body size, use of

Alcohol Absorption

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medication, and nutritional status Excess alcohol goes back into the blood

Alcohol Absorption

Alcohol Absorption

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Accumulation of acetaldehyde produces metabolic abnormalities • Inhibition of protein synthesis • Increase in harmful free-radical production • Increased lipid peroxidation • MEOS pathway becomes more active than ADH pathway during alcohol abuse • MEOS enzymes prioritize alcohol metabolism, leaving the drugs to accumulate

How are Macronutrients Synthesized? Gluconeogenesis

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During the process of Anabolism chemically simple compounds are used to synthesize more complex body proteins, lipids and carbohydrates

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Gluconeogenesis: making new glucose from non-glucose substrates • Primarily from glucogenic amino acids • Small amount from glycerol (triglyceride) • Maintains blood glucose during sleep, fasting, trauma, and exercise Protein catabolism for glucose production can draw on vital tissue proteins (skeletal and heart muscles and organ proteins)

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Lipogenesis

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Lipogenesis (de novo synthesis) is making fat from nonfat substances such as carbohydrates, amino acids, and alcohol • When consuming excess calories, acetyl CoA units form fatty acid chains • Fatty acids combine with

Amino Acid Synthesis

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glycerol to form triglycerides Mostly occurs in liver cells

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Body makes carbon skeleton of nonessential amino acids (NEAA) Amine group comes from transamination Synthesis of NEAA occurs only when the body has enough energy and nitrogen Since essential amino acids cannot be synthesized, they must be consumed

Amino Acid Synthesis

How Do Feeding and Fasting Affect Metabolism?

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Cycles of feeding and fasting • While we sleep body continues its metabolic processes drawing upon stored energy • In the morning the body receives infusion of new energy sources

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Anabolic state: bloodstream is enriched with glucose, fatty acids, and amino acids • Glucose is stored as glycogen • When glycogen stores are saturated, remaining glucose is stored as triglycerides

Metabolic Responses to Feeding

Metabolic Responses to Feeding

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Metabolic Responses to Fasting

Metabolic Responses to Starvation

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Fatty acids are stored as triglycerides mostly in adipose tissues Amino acids are deaminated and carbon skeletons are converted to fatty acids for storage as triglycerides

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Liver glycogen is broken down, releasing glucose into the blood Most cells can switch to using fatty acids as fuel to conserve glucose for brain and other cells that rely on glucose as fuel Ketones form as acetyl CoA units are blocked from entering TCA cycle Glucose synthesis from glucogenic amino acids and glycerol

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The body shifts to survival mode Blood glucose is maintained to support brain and red blood cells Decline in activity, body temperature, and ...