FFP1- Carbohydrates Proteins Lipids.pptx

Royal College of Surgeons in Ireland – Medical University of Bahrain FFP1-22: Proteins, Carbohydrates and Lipids Module :FFP1 Code :FFP1-101 Class : MedYear1 semester 1 Lecturer : Dr Jeevan Shetty Date : 28 Sep 2023 Pre-class activity- watch these short videos https://www.youtube.com/watch?v=_qf_r5...

Royal College of Surgeons in Ireland – Medical University of Bahrain FFP1-22: Proteins, Carbohydrates and Lipids Module :FFP1 Code :FFP1-101 Class : MedYear1 semester 1 Lecturer : Dr Jeevan Shetty Date : 28 Sep 2023 Pre-class activity- watch these short videos https://www.youtube.com/watch?v=_qf_r5EVP6U&ab_channel=g reatpacificmedia https://www.youtube.com/watch?v=_ExVXeovB6s&ab_channel= WhatsUpDude https://www.youtube.com/watch? v=Sb59aH4gknY&ab_channel=7activestudio Royal College of Surgeons in Ireland – Medical University of Bahrain Learning Outcomes 1.Outline the classification of amino acids 2.Describe the primary, secondary, tertiary and quaternary structure of proteins 3.Explain the concepts of ‘native conformation’ and post-translational modification of a protein 4.Describe the key structural features of monosaccharides 5.Define the glycosidic bond with the structure of a disaccharide 6.Describe the structure and function of polysaccharides 7.Describe the key structural features of fatty acids and the acylglycerides (mono, di and tri) 8.Distinguish between the classifications of lipids: phospholipids, sphingolipids, sterols and lipoproteins FFP-1 Proteins, Carbohydrates & Lipids GIHEP CNS BMF Endocrin e YEAR-1 & 2 Cardio Renal Respiratory SC Prep for clinical practice • Chemical properties depend on the nature of the side-chain [the R group] • R Group Properties: The basic structure of an Amino acid – Polarity – Hydrophobic/philic (water hating/loving) – Acidic (H+ Donor) –ve at neutral pH – Basic (H+ Acceptor) +ve at neutral pH Amino acid SIDE Chain (R) properties AA properties determine how they will behave once have been inserted into a polypeptide 4 CHARACTERISTICS OF THE SIDE CHAINS (R GROUPS) Amino Acids Polar Hydrophilic Non-polar Hydrophobic Aliphatic (hydrocarbon chain) Aromatic Basic Neutral (ring structure) Acidic (Positive charge) (Negative charge) Lysine Arginine Histidine Aspartic acid (Aspartate) Glutamic acid (Glutamate) OH Glycine Alanine Valine Leucine Isoleucine Methionine Proline Phenylalanine Tryptophan Serine Threonine Tyrosine Asparagine Glutamine Cysteine 5 COONH3+ Some more characteristics • • • • • The small amino acids: glycine and alanine The branched amino acids: valine, leucine, isoleucine The sulphur-containing amino acids: cysteine and methionine The amino acid found at a bend in a protein: proline Amino acids that can be phosphorylated: serine, threonine and tyrosine • Amino acids that can be glycosylated: asparagine, serine and threonine • Amino acid that can be nitrosylated: cysteine 6 Essential amino acids • • • • • AAs are also categorised as essential These AAs cannot be synthesised in the body They must come from the diet Some AAs are ‘conditionally’ essential: their rate of synthesis may not be sufficient to meet demand under all conditions and may need to come from the diet Non-essential amino acids are those that can be synthesised from other amino acids or precursors Essential Non-essential Methionine Alanine Arginine* Aspartic acid Threonine Asparagine Tryptophan Cysteine Valine Glutamic acid Isoleucine Glycine Leucine Proline Phenylalanine Serine Histidine Tyrosine Lysine Glutamine* *Conditionally essential in children MATT VIL PHLY 7 Protein structure Primary structure Primary Secondary Tertiary Quaternary • Amino acids formed into a polypeptide chain • Amino acids linked together with peptide bonds • This bond is formed between the carboxyl group of one amino acid and the amino group of the next amino acid • The peptide bond is C(O) - NH • Chain has direction: – Start = amino terminus = N terminus – End = carboxyl terminus = C terminus Secondary structure Examples a helix: collagen a helix: keratin in hair • Amino acid sequence controls folding • Has a regular repetitive folding pattern • Hydrogen bonds stabilise • Alpha (a) helix b sheet: silk • Beta (b) pleated sheet 9 Tertiary structure- E.g. Myoglobin • This is further folding of the polypeptide chain • Folding into a globular form • Compact folded structure – hydrophobic AAs on the inside – hydrophilic AAs on the outside • It stabilised by a wide range of bonds and interactions between the side chains of amino acids: – Disulphide bonds (between 2 cysteines) – Hydrophobic interactions – Ionic bond – Hydrogen bonds Globular protein: • Combination of secondary structural elements (a-helices, bsheets) • connected by loops • Form super-secondary structures(domains or motifs) Quaternary structure • It is the arrangement of protein subunits in a multi-meric protein • The 3D arrangement of more than one tertiary polypeptide • Consist of 2 or more polypeptide chains • Polypeptide may be the same or different • Held together by – Non-covalent interactions – Inter-chain disulphide bonds Eg; Hemoglobin Native conformation • It is the functional fully folded protein structure • It is a unique three-dimensional structure determined by – Primary structure – Secondary structure – Tertiary structure – Sometimes quaternary structure • It determines the biological function of the protein – Catalysis – Protection – Regulation – Signal transduction – Storage – Transport Denaturation? Post-translational modifications (PTM) • Increases the diversity of the proteome • Chemical modification of a protein after translation • A functional group is attached to an amino acid • Results in a change in protein function • Phosphorylation: + phosphate on serine and/or threonine or tyrosine residue = phosphoprotein • Glycosylation: + sugar group on asparagine or serine or threonine residues = glycoprotein • Acylation: + fatty acid • Ubiquitination: + ubiquitin = death signal • Nitrosylation: + NO (nitric oxide) Some Common PTM of proteins 13 A little bit of context: Abnormal protein aggregates can cause disease • Results from misfolding of proteins into fibrils • Fibrils = amyloid • Amyloid can be formed from over 20 proteins • Deposition in different tissues • Presence of misfolded proteins in the brain: Alzheimer’s Disease (Adapted from Meisenberg and Simmons 3rd ed) 14 What are carbohydrates (saccharide)? • They are molecules that contain carbon (C), hydrogen (H), and oxygen (O) atoms • A single saccharide is called a monosaccharide • Two monosaccharides linked together is a disaccharide • An oligosaccharide is a few linked monosaccharides – Can be associated with proteins (glycoproteins) or lipids (glycolipids) • Polysaccharides consist of many monosaccharides eg cellulose or glycogen 15 Monosaccharides • Simple sugar units • Empirical formula = (CH2O)n where n = 3 – 7 carbons • n = 3 carbons: triose • n = 5 carbons: pentose • n = 6 carbons: hexose • They are polyhydroxy aldehydes (aldose) or ketones (ketose) 16 Hexoses (C6H12O6) ISOMERS Aldo group • Same chemical formula but different structures • These structures are called isomers • Dietary sources: • Glucose: Fruit juices, starch, glycogen, lactose, maltose, cane sugar • Fructose: Fruit juices, honey, cane sugar • Galactose: Milk (Lactose) • Mannose: Plants and gums Keto group Glucose Glucose, an aldose 17 Fructose Fructose, a ketose H Monosaccharides like to form a ring: cyclisation 6 CH2OH O H H 4 b = beta H HO 3 OH is up, bird in the sky 2 H OH H 6 CH2OH O H H 5 H 4 a = alpha 1 H HO HO 3 H 2 HO 3 H 1 HO H H OH 5 2 O 1C OH is down, fish in the sea OH OH Let's have a 18look at this 4 5 OH H OH OH 6 CH2OH • In an aldose its all happening at carbon 1 = C1 • C1 in aldose = carbonyl carbon • C1 in cyclised aldose = anomeric carbon • Have an alpha anomeric carbon • Have a beta anomeric carbon • In a ketose it all happens at carbon 2 = C2 Disaccharides & glycosidic bond: bond between 2 sugars • The name or type of bond depends on – The numbers of the connected carbons – The position of the anomeric hydroxyl group • If the –OH group is in the alpha configuration, it is an alpha (a) bond • If the –OH group is in the beta configuration, it is a beta (b) bond Example: Lactose = b-galactose + glucose – Bond is between carbon 1 of b-galactose and carbon 4 of glucose: condensation event – Bond (linkage) is b (1→ 4) glycosidic bond • Carbohydrates can also bind to noncarbohydrate structures     Purines and pyrimidine bases in nucleic acids Aromatic rings e.g. in steroids Proteins: glycoproteins Lipids: glycolipids n = 3-12: Oligosaccharides n > 12 – hundreds: Polysaccharides Polysaccharides • n > 12 – hundreds • Variations can occur in the chain • Monosaccharides • Glycosidic bonds • Branch points • Structure • Example: Amylopectin branched every 24-30 residues  1-6  1-4  1-4 Polysaccharide Functions • • • • Storage in animals: – Glycogen: A homopolymer of glucose. Branched every 12-14 residues ( 1-4,  1-6) Storage in plants: – Starch: A homopolymer of glucose; composed of: • Amylopectin (80-85%) branched every 24-30 residues ( 1-4,  1-6) • Amylose (15-20%) non-branched helical structure ( 1-4) Structure in plants: – Cellulose: Homopolymer of glucose. Long straight chains (β1-4) Structure in invertebrates: – Chitin: Homopolymer of n-acetyl-glucosamine Lipids: Lipids are a heterogeneous group of water-insoluble (hydrophobic) The fed and fasting states: creating energy. organic molecules Functions • Major source of energy in the body • Structural components of cells and organelles • Involved in cellular signaling events e.g. – Steroids – Prostaglandins – Leukotrienes Classification of Lipids [a] Fatty acids and their derivatives • prostaglandins • leukotrienes [b] Lipids containing glycerol • Neutral lipids: mono-, di-, tri-acylglycerol (triglycerides) • Charged lipids: Phospholipids [c] Lipids not containing glycerol • Steroids • Sphingolipids • Terpenoids [d] Lipoproteins and lipopolysaccharides Chain lengths of Fatty acids • • • Number before colon = number of carbons in chain Number after colon = numbers and positions of double bonds relative to carboxyl carbon E.g. Arachidonic acid 20:4 (5,8,11,14) – 20 carbon chain – 4 double bonds between carbons 5-6, 89, 11-12 and 14-15 It is also an  -6 (n-6) fatty acid: terminal double bond is 6 bonds in from the carbon Essential FAs (EFAs) • Nutritionally essential as we cannot synthesise them • Linoleic acid ( -6 or omega-6): – CH3(CH2)4(CH=CHCH2)2(CH2)6COOH 18:2(n-6) •  -linolenic acid ( -3 or omega-3): – CH3CH2(CH=CHCH2)3(CH2)6COOH 18:3(n-3) • EFA deficiency (rare) – Scaly dermatitis (ichthyosis) – Visual and neurologic abnormalities Arachidonic acid Signalling FAs Leukotrienes Prostaglandins (PG) • • • • • • • Eicosanoids (PUFA -20) Synthesis: Arachidonic acid (a 20:4 FA) via COX (cyclooxygenase) Potent Short half-life (seconds) Multiple roles – Inflammatory – Platelet homeostasis • • 28 Part of eicosanoid family Synthesis: arachidonic acid via LOX (lipoxygenase) Longer half-life (up to 4 hours) Multiple roles – Inflammatory – Neutrophil adhesion Monoacyl, Diacyl & Triacyl glycerol, • Monoacyl glycerol – Breakdown product of TAG in fat digestion • DAG (Diacylglycerol) – Potent intracellular signaller – Mobilisation of calcium • Triglycerides (Triacylglycerols: TAG) - Made up of 3 FAs and glycerol - The principal storage form of energy in the body - Stored in adipose tissue Phospholipids (Phosphoglycerates) Glycerophospholipid • Major component of cell membrane • E.g.-Lecithin 30 Sphingolipids Steroids • • Contain a characteristic fused ring system with a hydroxyl or keto group on carbon 3 Major steroid classes – Cholesterol (27 carbons) – Bile acids (24 carbons) – Progesterone and adrenocortical steroids (21 carbons) – Androgens (19 carbons) – Estrogens (18 carbons) Functions of cholesterol • Metabolic precursor of • Vitamin D • Bile-acids • Steroid hormones • It plays a vital role in the structure of membranes • We need a constant supply of cholesterol Lipoproteins • • • Spherical particles found in plasma that transport lipids, including cholesterol Hydrophobic core of triacylglycerols and cholesteryl esters Phospholipid layer associated with cholesterol and protein https://www.youtube.com/watch? v=qglYWog3o8M&ab_channel=FocusMedica Lipoproteins Classes & Characteristics FFP-1 Proteins, Carbohydrates & Lipids GIHEP CNS BMF Endocrin e YEAR-1 & 2 Cardio Renal Respiratory SC Prep for clinical practice Summary • Amino acid classification • Protein structure • Primary • Secondary • Tertiary • Quaternary • • • • • Simple sugars are monosaccharides = building block of carbohydrates Polysaccharides are composed of Medical Sciences by Jeannette Naish​hundreds to thousands of Chapter 2 to help your learning monosaccharides The building block of lipids is the fatty acid chain More complex lipids have glycerol in their structure The most important sterol is cholesterol