Major groups of organic compounds - continued Lecture 10 Modified from books, journals and internet resources.

Major groups of organic compounds - continued

Lecture 10

Modified from books, journals and internet resources

Signaling

• lipid signaling vital part of the cell signaling• occur via activation of nuclear receptors• several different lipid categories have been

identified as signaling molecules and cellular messengers

• sphingosine-1-phosphate (sphingolipid derivative) from ceramide potent messenger molecule involved in regulating calcium mobilization, cell growth, apoptosis

continued

• diacylglycerol(DAG) and the phosphatidylinositol phosphates (PIPs), calcium-mediated activation of protein kinase C

• prostaglandins, arachidonic acid -derived fatty acids involved in inflammation and immunity

• steroid hormones (estrogen, testosterone and cortisol) modulate a host of functions such as reproduction, metabolism and blood pressure

Other functions

• "fat-soluble" vitamins (A, D, E and K) isoprene-based lipids are essential nutrients stored in the liver and fatty tissues diverse range of functions

• Polyprenols and their phosphorylated derivatives transport of oligosaccharides across membranes

• Cardiolipins a subclass of glycerophospholipids abundant in the inner mitochondrial membrane activate enzymes involved with oxidative phosphorylation

Nutrition - From Food to the Bloodstream

• Almost all foods contain some fat• Even quintessential fat-free foods like carrots and lettuce

contain small amounts of fat• how important fats are for life• cholesterol starting point to make estrogen,

testosterone, vitamin D, and other vital compounds• Fat and cholesterol can't dissolve in water or blood• body gets around this basic chemistry problem by

packaging fat and cholesterol into tiny, protein-covered particles called lipoproteins

• most important ones are low-density lipoproteins, high-density lipoproteins, and triglycerides

continued

• Low-density lipoproteins (LDL) carry cholesterol from the liver to the rest of the body

• Cells latch onto these particles and extract fat and cholesterol from them

• too much LDL cholesterol in the blood these particles can form deposits in the walls of the coronary arteries and other arteries throughout the body = plaque

• LDL cholesterol often referred to as bad, or harmful, cholesterol

continued

• High-density lipoproteins (HDL) scavenge cholesterol from the bloodstream, from LDL, and from artery walls and ferry it back to the liver for disposal

• HDL cholesterol referred to as good, or protective, cholesterol

• Triglycerides make up most of the fat that you eat and that travels through the bloodstream

• the body's main vehicle for transporting fats to cells• triglycerides important for good health; an excess of

triglycerides can be unhealthy

How Fat and Cholesterol in Food Affect Blood Levels

• types of fat in the diet determine to a large extent the amount of total and LDL cholesterol in the bloodstream

• Cholesterol in food matters but not nearly as much• Good Fats • Unsaturated fats = good fats because they can improve

blood cholesterol levels, ease inflammation, stabilize heart rhythms, and play a number of other beneficial roles

• Unsaturated fats are predominantly found in foods from plants, such as vegetable oils, nuts, and seeds

• They are liquids at room temperature

Two types of unsaturated fats

• Monounsaturated fats high concentrations in canola, peanut, and olive oils; avocados; nuts (almonds, hazelnuts, and pecans) and seeds such as pumpkin and sesame seeds

•

continued

• Polyunsaturated fats • in high concentrations in sunflower, corn, soybean, and

flaxseed oils, and also in foods such as walnuts, flax seeds, and fish

• Omega-3 fats important type of polyunsaturated fat• body can't make these, so they must come from food• omega-3 fats fish two or three times a week• plant sources of omega-3 fats chia seeds (sold as

Salvia), flax seeds, walnuts, and oils such as flaxseed, canola, and soybean

Omega-3 fatty acids

• essential fats—the body can't make them from scratch but must get them from food

• integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes

• starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation

• bind to receptors in cells that regulate genetic function• prevent heart disease and stroke, may help control

lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions

continued

• Three main omega-3s: • Eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA) mainly from fish • Alpha-linolenic acid (ALA) most common

omega-3 fatty acid in most Western diets• in vegetable oils and nuts (especially walnuts),

leafy vegetables, and some animal fat, especially in grass-fed animals

• human body generally uses ALA for energy, and conversion into EPA and DHA is very limited

continued

• The strongest evidence for a beneficial effect of omega-3 heart disease

• Omega-3 fats appear to help the heart beat at a steady clip and not veer into a dangerous or potentially fatal erratic rhythm

• arrhythmias cause most of the 500,000-plus cardiac deaths that occur each year in the United States

• Omega-3 fats lower blood pressure and heart rate, improve blood vessel function, and, at higher doses, lower triglycerides and may ease inflammation, which plays a role in the development of atherosclerosis

continued

• clinical trials on effect of fish or fish oils on heart disease• heart attack survivors who took a 1-gram capsule of

omega-3 fats every day for three years were less likely to have a repeat heart attack, stroke, or die of sudden death than those who took a placebo

• the risk of sudden cardiac death was reduced by about 50 percent

• Another study participants who took EPA plus a cholesterol-lowering statin were less likely to have a major coronary event (sudden cardiac death, fatal or nonfatal heart attack, unstable angina, or a procedure to open or bypass a narrowed or blocked coronary artery) than those who took a statin alone

continued

• Most Americans take in far more of another essential fat—omega-6 fats—than they do omega-3 fats

• A study the ratio of omega-6 to omega-3 fats wasn't linked with risk of heart disease because both of these were beneficial

• Many other studies and trials in humans also support cardiovascular benefits of omega-6 fats

• evidence that omega-6 fats also positively influence cardiovascular risk factors and reduce heart disease

continued

• analysis examination of effects of carbohydrates and various fats on blood lipid levels

• polyunsaturated and monounsaturated fats were eaten in place of carbohydrates these good fats decreased levels of harmful LDL and increased protective HDL

• Trial for Heart Health showed that replacing a carbohydrate-rich diet with one rich in unsaturated fat (predominantly monounsaturated fats) lowers blood pressure, improves lipid levels, and reduces the estimated cardiovascular risk

continued

• Most people don't get enough of these healthful unsaturated fats each day

• targets 10 to 25 percent of calories from monounsaturated fats and 8 to 10 percent of calories from polyunsaturated fats

• good rule of thumb choose unsaturated fats over saturated whenever possible

What foods are good sources of omega-3 fatty acids? How much do I need to eat of these foods

to get enough omega-3s• types of omega-3 fatty acids in our diets:• alpha-linolenic acid (ALA) in some vegetable oils, such

as soybean, rapeseed (canola), and flaxseed, and in walnuts

• ALA in some green vegetables, such as Brussels sprouts, kale, spinach, and salad greens

• eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fatty fish

• body partially converts ALA to EPA and DHA. • We do not know whether vegetable or fish omega-3 fatty

acids are equally beneficial, although both seem to be beneficial

What are omega-6 fatty acids? Should I be concerned about the ratio of omega-6 fatty acids to

omega-3 fatty acids in my diet?

• Omega-6 fatty acids polyunsaturated fatty acids, essential nutrients (we must obtain them from food)

• common sources include safflower, corn, cottonseed, and soybean oils

• Omega-6 fatty acids lower LDL cholesterol (the "bad" cholesterol) and reduce inflammation, protective against heart disease

Is it better to get omega-3 fatty acids from food or from supplements?

• Certainly foods• plants and fish that contain omega-3 fats have other

good nutrients, such as protein, vitamins and minerals• not eating fish or other foods rich in omega-3 fatty acids

consider taking an omega-3 supplement of 500 mg per day

• fish oil is used in supplements, but there are also vegetarian supplements that have ALA

• Studies people who have already had a heart attack may benefit from higher doses of omega-3 supplements (basically, double the 500 mg)

Bad Fats

• Our bodies make all the saturated fat we need, so we don't need to eat any of it

• saturated fat can be in the bad category we don't need to eat any of it, and it has undesirable effects in cardiovascular disease

• developed countries saturated fats come mainly from meat, seafood, and whole-milk dairy products (cheese, milk, and ice cream)

• few plant foods are also high in saturated fats coconut and coconut oil, palm oil, and palm kernel oil

continued

• Saturated fats boost total cholesterol by elevating harmful LDL

• general rule keep your intake of saturated fats as low as possible.

• Red meat and dairy fats main sources of saturated fat in our diets

Very Bad Fats

• Trans fatty acids (trans fats) made by heating liquid vegetable oils in the presence of hydrogen gas = process called hydrogenation

• Partially hydrogenating vegetable oils makes them more stable and less likely to spoil

• also converts the oil into a solid• Partially hydrogenated oils can also withstand

repeated heating without breaking down, making them ideal for frying fast foods (fully hydrogenating a vegetable oil creates a fat that acts like a saturated fat) partially hydrogenated oils have been a mainstay in restaurants and the food industry

continued

• trans fats in the American diet come from commercially prepared baked goods, margarines, snack foods, and processed foods, along with French fries and other fried foods prepared in restaurants and fast food franchises

• Trans fats worse for cholesterol levels than saturated fats because they raise bad LDL and lower good HDL

• fire inflammation, an overactivity of the immune system that has been implicated in heart disease, stroke, diabetes, and other chronic conditions

• even small amounts of trans fat in the diet can have harmful health effects

continued

• For every extra 2 percent of calories from trans fat daily—about the amount in a medium order of fast-food French fries—the risk of coronary heart disease increases by 23 percent

• Eliminating trans fats from the U.S. food supply could prevent between 6 and 19 percent of heart attacks and related deaths, or more than 200,000 each year. (13)

• The average American eats about six grams of trans fats a day

• Ideally that should be under two grams a day, or zero if possible

Cholesterol in Food

• most people make more cholesterol than they absorb from their food

• scientific studies shows only a weak relationship between the amount of cholesterol a person consumes and his or her blood cholesterol levels

continued

• studies of more than 80,000 female nurses Harvard researchers found that consuming about an egg a day was not associated with higher risk of heart disease (too few women in the study were eating more than an egg a day to evaluate the effects of higher egg intakes)

• Among women in this study with diabetes and in another study of men with diabetes, higher egg consumption has been associated with increased risks of heart disease

continued

• most people amount of cholesterol eaten has only a modest impact on the amount of cholesterol circulating in the blood

• some people blood cholesterol levels rise and fall very strongly in relation to the amount of cholesterol eaten

Dietary Fats and Heart Disease: Beyond the "30 Percent" Recommendation

• American Heart Association to reduce dietary fat

• limiting fat intake to under 30 percent of daily calories

• problem with a generic lower fat diet it prompts most people to stop eating fats that are good for the heart along with those that are bad for it

• In place of fats many people turn to foods full of easily digested carbohydrates, or to fat-free products that replace healthful fats with sugar and refined carbohydrates

continued

• Women's Health Initiative Dietary Modification Trial (February 8, 2006, Journal of the American Medical Association) eight-year trial (included almost 49,000 women) found virtually identical rates of heart attack, stroke, and other forms of cardiovascular disease in women who followed a low-fat diet and in those women who didn't

• women on the low-fat diet didn't lose—or gain—any more weight than women who followed their usual diets

continued

• Many of these studies the type of fat in the diet

• Ounce for ounce trans fats are far worse than saturated fats when it comes to heart disease

• One study replacing just 30 calories of carbohydrates (7 grams) every day with 30 calories of trans fats (4 grams) nearly doubled the risk for heart disease

• Saturated fats increased the risk as well, but not nearly as much

continued

• For good fats consistent evidence that higher intake of either monounsaturated or polyunsaturated fat (especially the latter) lowers the risk for heart disease

• replacing 80 calories of carbohydrates with 80 calories of either polyunsaturated or monounsaturated fats lowered the risk for heart disease by about 30 to 40 percent

Dietary Fats and Cancer

• Heart disease is not the only condition that has been linked with fat intake. Researchers once suspected an association between dietary fat and certain cancers

• Breast Cancer • early 1980s most nutrition experts believed that

dietary fat was a major cause of breast cancer• based on international comparisons showing higher

breast cancer rates in countries with higher per capita fat intake

• The Women's Health Initiative Dietary Modification Trial designed to examine the effect of a low-fat diet on the development of breast cancer showed similar rates of breast cancer in women eating a low-fat diet and in those eating a "regular" diet

continued

• studies—including those by Harvard researchers— of different types of fat have largely failed to find a link with breast cancer, some evidence suggests that animal fat intake may be linked to higher risk of breast cancer

• red meat and high-fat dairy products may contain other factors, such as hormones, that increase risk of breast cancer

• European studies have reported suggestive findings of lower breast cancer risk among women with a high intake of monounsaturated fats (mainly in the form of olive oil)

Colon Cancer

• Although fat intake doesn't seem to increase colon cancer risk, there is convincing evidence that high consumption of red meat (beef, pork, and lamb) and processed meat (hot dogs, bacon, and deli meats) does increase colon cancer risk

• best to limit red meat consumption to no more than 18 ounces per week, and to avoid processed meats.

Cancers - continued• Prostate Cancer • the exact connection between dietary fat and prostate cancer is far

from clear• some evidence that diets high in animal fat and saturated fat

increase prostate cancer risk• much more research is needed to clear up the exact links between

dietary fat and prostate cancer• Other Cancers • Preliminary research has also linked the intake of certain kinds fat

with other cancers, though much more research is needed to confirm these results

• Harvard researchers found that a high intake of trans fats was associated with risk for non-Hodgkin's lymphoma

Dietary Fat and Other Chronic Conditions

• small but growing body of work on the effects of dietary fats on conditions such as osteoporosis, age-related memory loss, macular degeneration, multiple sclerosis, infertility,and other chronic conditions

Dietary Fat and Obesity • common belief the more fat you eat, the more weight and body

fat you gain• nutrition advice given to people over the past few decades

lowering total fat intake while increasing carbohydrate intake• food fat equals body fat isn't completely true, and the advice has

been misguided (Harvard research)• while Americans have gradually decreased the proportion of

calories they get from fat over the past few decades rates of obesity have increased steeply

• prudent recommendation for losing weight or maintaining a healthy weight be mindful of the amount of food you eat in relation to the amount of calories you burn in a day

• moderate intake of fats, with an emphasis on healthful unsaturated fats, fits in fine with a weight-loss or weight-maintaining diet

The Bottom Line: Recommendations for Fat Intake

• Avocado is a great source of healthy unsaturated fats

• basic message is simple: Out with the bad, in with the good

• limit the amount of trans and saturated fats in your diet• there is no good evidence that replacing saturated fat

with carbohydrates will protect you against heart disease• solid proof that replacing saturated fat with unsaturated

fats will help• eliminate trans fats from partially hydrogenated oils

continued

• Check food labels for trans fats; avoid fried fast foods• cutting back on red meat and full-fat dairy foods• replacing red meat with beans, nuts, poultry, and fish

whenever possible, and switching from whole milk and other full-fat dairy foods to lower fat versions

• In place of butter, use liquid vegetable oils rich in polyunsaturated and monounsaturated fats in cooking and at the table

• Eat one or more good sources of omega-3 fats every day—fish, walnuts, canola or soybean oil, ground flax seeds or flaxseed oil

Proteins

• large organic compounds made of amino acids

• arranged in a linear chain• joined together by peptide bonds between

the carboxyl and amino groups of adjacent amino acid residues

• sequence of amino acids in a protein is defined by a gene and encoded in the genetic code

continued

• proteins are essential parts of organisms and participate in every process within cells

• Many proteins enzymes that catalyze biochemical reactions and are vital to metabolism

• structural or mechanical functions (actin and myosin in muscle and the proteins in the cytoskeleton)

• cell signaling, immune responses, cell adhesion, and the cell cycle

continued

• necessary in animals' diets, since animals cannot synthesize all the amino acids they need and must obtain essential amino acids from food

• Digestion animals break down ingested protein into free amino acids that are then used in metabolism

continued

• linear polymers built from 20 different α-amino acids

• All amino acids common structural features• α carbon an amino group, a carboxyl group,

and a variable side chain are bonded• (proline differs from this basic structure as it

contains an unusual ring)• The side chains of the standard amino acids

have different chemical properties that produce three-dimensional protein structure and are therefore critical to protein function

continued

• Protein generally used to refer to the complete biological molecule in a stable conformation

• peptide generally reserved for a short amino acid oligomers often lacking a stable three-dimensional structure

continued

• Proteins assembled from amino acids using information encoded in genes

• Each protein unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein

• genetic code set of three-nucleotide sets called codons and each three-nucleotide combination stands for an amino acid (e.g. AUG stands for methionine)

• DNA contains four nucleotides, the total number of possible codons is 64 there is some redundancy in the genetic code, with some amino acids specified by more than one codon

The DNA sequence of a gene encodes the amino acid sequence of a protein.

Protein synthesis

• synthesizing a protein from an mRNA template = translation

• mRNA is loaded onto the ribosome, read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule (which carries the amino acid corresponding to the codon it recognizes)

• size of a synthesized protein measured by the number of amino acids it contains and by its total molecular mass, which is normally reported in units of daltons

continued

• Yeast proteins are on average 466 amino acids long and 53 kDa in mass

• largest known proteins the titins = a component of the muscle sarcomere, with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids

Protein structure

• Most proteins fold into unique 3-dimensional structures

• Primary structure the amino acid sequence

• Secondary structure regularly repeating local structures stabilized by hydrogen bonds

• common example the alpha helix

continued

• Tertiary structure the overall shape of a single protein molecule

• the spatial relationship of the secondary structures to one another

• Quaternary structure the shape or structure that results from the interaction of more than one protein molecule

Three-dimensional structure of the protein triose phosphate isomerase

continued

• Proteins are not entirely rigid molecules• may shift between several related structures while they

perform their functions• tertiary or quaternary structures are usually referred to

as "conformations“• changes induced by the binding of a substrate

molecule to an enzyme's active site, or the physical region of the protein that participates in chemical catalysis

• in solution all proteins also undergo variation in structure through thermal vibration and the collision with other molecules

Classes of proteins

• informally divided into three main classes, which correlate with typical tertiary structures:

• globular proteins almost all are soluble and many are enzymes

• fibrous proteins often structural• membrane proteins serve as receptors or

provide channels for polar or charged molecules to pass through the cell membrane

Functions

• the chief actors within the cell• carrying out the duties specified by the information

encoded in genes• set of proteins expressed in a particular cell or cell type

is known as its proteome• chief characteristic of proteins that allows their diverse

set of functions ability to bind other molecules specifically and tightly

• region of the protein responsible for binding another molecule the binding site

• binding ability mediated by the tertiary structure of the protein

continued

• Proteins can bind to other proteins as well as to small-molecule substrates

• proteins bind specifically to other copies of the same molecule oligomerize form fibrils (often in structural proteins)

• Protein-protein interactions regulate enzymatic activity, control progression through the cell cycle, allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function

• ability of binding partners to induce conformational changes in proteins allows the construction of enormously complex signaling networks

Enzymes

• best-known role of proteins in the cell as enzymes (catalyze chemical reactions)

• Enzymes usually highly specific and accelerate only one or a few chemical reactions

• carry out most of the reactions involved in metabolism• Some enzymes act on other proteins to add or

remove chemical groups = post-translational modification

• molecules bound and acted upon by enzymes = substrates

• region of the enzyme that binds the substrate and contains the catalytic residues = the active site

Cell signaling and ligand transport

• Many proteins are involved in the process of cell signaling and signal transduction

• E.g. insulin extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues

• membrane proteins act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell

continued

• Antibodies protein components of adaptive immune system

• main function is to bind antigens, or foreign substances in the body, and target them for destruction

• enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction antibodies have no such constraints

continued

• Many ligand transport proteins bind particular small biomolecules and transport them to other locations in the body

• Ligand = a molecule, as an antibody, hormone, or drug, that binds to a receptor

• Proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues

continued

• example of a ligand-binding protein haemoglobin, which transports oxygen from the lungs to other organs and tissues

• Transmembrane proteins serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions

Structural proteins

• confer stiffness and rigidity to otherwise-fluid biological components

• Most are fibrous proteins; for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that comprise the cytoskeleton

• Collagen and elastin critical components of connective tissue such as cartilage, and keratin is found in hard or filamentous structures such as hair, nails

• motor proteins (myosin, kinesin, and dynein) capable of generating mechanical forces contracting muscles

Proteomics and bioinformatics

• total complement of proteins present at a time in a cell or cell type = known as its proteome

• study of such large-scale data sets defines the field of proteomics

• systematic attempt to determine the structures of proteins representing every possible fold is known as structural genomics

• large amount of genomic and proteomic data available for a variety of organisms (including the human genome) allows researchers to efficiently identify homologous proteins in distantly related organisms by sequence alignment

continued

• field of bioinformatics seeks to assemble, annotate, and analyze genomic and proteomic data

• apply computational techniques to biological problems such as gene finding and cladistics

Protein in nutrition

• Most microorganisms and plants biosynthesize all 20 standard amino acids

• animals, (including humans) must obtain some of the amino acids from the diet

• enzymes in the biosynthetic pathways that synthesize certain amino acids (as aspartokinase, which catalyzes the first step in the synthesis of lysine, methionine, and threonine from aspartate) not present in animals

• essential amino acids: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, and lysine

continued

• animals amino acids are obtained through the consumption of foods containing protein

• Ingested proteins broken down through digestion, which typically involves denaturation of the protein through exposure to acid and hydrolysis by enzymes called proteases

• Some ingested amino acids used for protein biosynthesis, others are converted to glucose through gluconeogenesis

• Some fed into the citric acid cycle• starvation body's own proteins to be used to support

life (particularly in muscle)• Amino acids important dietary source of nitrogen

Proteins and music • Imagine the mRNA to be like a long piece of magnetic

recording tape, and the ribosome to be like a tape recorder

• As the tape passes through the playing head of the recorder, it is "read" and converted into music, or other sounds...

• When a "tape" of mRNA passes through the "playing head" of a ribosome, the "notes" produced

• are amino acids and the pieces of music they make up are proteins

• http://www.tjmitchell.com/stuart/dna.html