CHO and CHON Trans. PDF

*SUMMARY* ▪ Except for proline, each amino acid has:  The important disaccharides include maltose  A carboxyl group (glucosyl–glucose), an intermediate in the  An amino group digestion of starch; sucrose (gluco...

*SUMMARY* ▪ Except for proline, each amino acid has:  The important disaccharides include maltose  A carboxyl group (glucosyl–glucose), an intermediate in the  An amino group digestion of starch; sucrose (glucosyl–fructose),  A distinctive side chain (called the R-group) important as a dietary constituent containing ▪ All three are bonded to the α-carbon atom fructose; and lactose (galactosyl–glucose), in ▪ The structure of the R-group dictates the function milk. of the amino acid in a protein  Starch and glycogen are storage polymers of glucose in plants and animals, respectively. Starch is the major metabolic fuel in the diet.  Complex carbohydrates contain other sugar derivatives such as amino sugars, uronic acids, and sialic acids. They include proteoglycans and glycosaminoglycans, which are associated with structural elements of the tissues, and glycoproteins, which are proteins containing NONPOLAR AMINO ACIDS oligosaccharide chains; they are found in many situations including the cell membrane. GLYCINE Has the smallest side chain (simplest amino acid) PROTEINS Used in the first step of heme synthesis Glycine + Succinyl CoA à δ-ALA ▪ Linear polymers of amino acids Used in synthesis of purines and creatine ▪ Perform diverse functions: Conjugated to bile acids, drugs, and other 1. Catalyst of chemical reactions - enzymes metabolites 2. Transport and storage - hemoglobin Major inhibitory neurotransmitter in the spinal cord 3. Coordinated motion - actin and myosin 4. Mechanical support - collagen and keratin 5. Immune protection - gamma globulins 6. Transmission of nerve impulses - neurotransmitters 7. Cell signaling - membrane receptors 8. Hormones – insulin, thyrotropin, ALANINE somatotropin Carrier of ammonia and of the carbons of pyruvate from skeletal muscle to liver PROTEOME Together with glycine, constitutes a major fraction ▪ The set of all the proteins expressed by an of free amino acids in the blood individual cell at a particular time Transamination of pyruvate forms alanine. The amino donor may be glutamate or aspartate. The PROTEOMICS other product thus is α-ketoglutarate or oxaloacetate. ▪ Aims to identify the entire complement of proteins elaborated bya cell under diverse conditions ▪ A major goal is the identification of proteins and of their posttranslational modifications whose appearance or disappearance correlates with physiologic phenomena, VALINE, LEUCINE, ISOLEUCINE aging, or specific diseases While these three are nutritionally essential amino acids, tissue aminotransferases reversibly AMINO ACIDS interconvert all three amino acids and their corresponding α-keto acids. ▪ More than 300 amino acids have been described Branched-chain amino acids whose metabolites ▪ Only 20 are commonly found in mammalian accumulate in maple syrup urine disease proteins  Essential Amino Acids – 8 must be present in the human diet, and thus are best termed “nutritionally essential.”  Non-Essential Amino Acids – other 12 “nutritionally nonessential” amino acids, while metabolically essential, need not be present in the diet STRUCTURE OF AMINO ACIDS PHENYLALANINE Accumulates in phenylketonuria Precursor of tyrosine TRYPTOPHAN Asparagine is the site for N-linked glycosylation of Has the largest side chain proteins Precursor for niacin, serotonin, and melatonin Glutamine is deaminated by glutaminase resulting in the formation of ammonia, and is a major carrier of nitrogen to the liver from peripheral tissues MNEMONIC: TRYPTOPHAN DERIVATIVES TRYp Mo Siya, ‘No? TRYptophan CYSTEINE Melatonin Contains a sulfhydryl group that is an active part of Serotonin many enzymes Niacin Participates in the biosynthesis of coenzyme A Two cysteines can be connected by a covalent METHIONINE disulfide bond to form cystine Source of methyl groups in metabolism While not itself nutritionally essential, cysteine is Involved in transfer of methyl groups as S- formed from methionine, which is nutritionally adenosylmethionine (SAM) essential. Precursor of homocysteine and cysteine ACIDIC AMINO ACIDS PROLINE Not an amino, but an imino acid ASPARTATE (D), GLUTAMATE (E) Contributes to the fibrous structure of collagen and Negatively charged at neutral pH because of the interrupts α-helices in globular proteins thus also carboxylate group known as the “helix-breaker” Participate in ionic interactions Serve as proton donors Glutamate is the precursor for GABA and glutathione UNCHARGED POLAR AMINO ACIDS SERINE, THREONINE, TYROSINE Recall that GABA is the major inhibitory NT in the Contain a polar hydroxyl group brain; Glutamate is excitatory (meron din sa MSG). Site for O-linked glycosylation and Glu → GABA is catalyzed by Gludecarboxylase phosphorylation of proteins Tyrosine is the precursor of several compounds: o Phenylalanine → Tyrosine → L-dopa → BASIC AMINO ACIDS Dopamine →Norepinephrine → Epinephrine HISTIDINE o Also a precursor for thyroxine and melanin Precursor of histamine Also used in the diagnosis of folic acid deficiency (FIGLU excretion test) Concentration in the brain hypothalamus varies in accordance with the circadian rhythm PHENYLALANINE / TYROSINE DERIVATIVES: ARGININE Pare, True Love Does Not Exist Precursor of creatinine, urea and nitric oxide Phenylalanine →Tyrosine → L-dopa → Dopamine → Norepinephrine → Epinephrine LYSINE Precursor of carnitine ASPARAGINE, GLUTAMINE Have a carbonyl group and an amide group that can also form hydrogen bonds 21st AMINO ACID – SELENOCYSTEINE Rigid and planar ▪ Found in a handful of proteins, including Generally, in the trans configuration certain peroxidases and reductases, where it Disrupted by hydrolysis through prolonged participates in the catalysis of electron exposure to a strong acid or base at elevated transfer reactions temperatures ▪ A selenium atom replaces the sulfur of its structural analog, cysteine ▪ Inserted into polypeptides during translation but is not specified by a simple three-letter codon PROPERTIES OF AMINO ACIDS: By convention, we name the protein from the amino terminus (N terminus) to the carboxy-terminus (C ▪ Except for glycine, all amino acids are chiral terminus) o L-configuration: all amino acids in proteins o D-configuration: bacterial cell walls, SECONDARY STRUCTURE antibiotics The folding of short (3–30 residue) contiguous segments of polypeptide into geometrically Chiral – Carbon that has 4 different groups around ordered units him. Glycine’s alpha carbon is not chiral or is Stabilized by hydrogen bonding Achiral since two H’s (which are similar) are attached around that carbon hence Gly has no chiral Alpha Helix center. All the rest are chiral, and if chiral it will Most common have a nonsuperimposable mirror image Spiral structure with polypeptide backbone (enantiomer). core, with side chains extending outward 3.6 AA per turn ▪ Amino acids can have negative, zero, or positive Disrupted by proline, AAs with large or charge depending on pH of the aqueous charged R-groups environment Examples: An amino acid bears no net charge (zwitterion) at o Keratin (100% α-helix) its isoelectric pH (pI) o Hemoglobin (80% α-helix) Because they can accept or donate protons, amino acids can serve as buffers in aqueous solutions Beta Sheet Amino acid residues form a zigzag or pleated Form II is the zwitterion for alanine (neutral charge pattern overall). Acidic amino acids have a pI < 7. Basic R groups of adjacent residues project in amino acids have pI > 7. opposite directions Sheets can be parallel or antiparallel ESSENTIAL AMINO ACIDS Examples: o Amyloid Amino acids whose intake is essential for proper o Immunoglobulin body function since they cannot be synthesized: Phenylalanine Histidine TERTIARY STRUCTURE Valine Arginine* Over-all 3-dimensional shape of the protein Tryptophan Leucine o Globular proteins vs Fibrous proteins Threonine Lysine The assembly of secondary structural units Isoleucine into larger functional units such as the mature Methionine polypeptide and its component domains Stabilized by disulfide bonds, hydrophobic Arginine is considered nutritionally semi-essential interactions, hydrogen bonds, and ionic Cystine and tyrosine can be synthesized in the interactions body, but only from essential amino acid precursors ESSENTIAL AMINO ACIDS MNEMONIC PVT TIM HALL, always ARGues, never TYRes. A is always ARGinine. T is never TYRosine. PROTEIN STRUCTURE: QUATERNARY STRUCTURE 1. PRIMARY STRUCTURE Number and types of polypeptide units of Determined by a protein’s amino acid oligomeric proteins and their spatial sequence arrangement Peptide bonds attach the α-amino group of o Monomeric vs Dimeric proteins one amino to the α-carbonyl group of another o Homodimers vs Heterodimers Peptide Bonds Partial double-bond character CHAPERONES Specialized group of proteins required for the proper folding of many species of proteins Prevent aggregation, thus providing an opportunity for the formation of appropriate secondary structural elements and their subsequent coalescence into a molten globule DENATURATION FIBROUS PROTEINS Results in the unfolding and disorganization of the protein’s secondary and tertiary COLLAGEN structures Most abundant protein in the body Not accompanied by hydrolysis of peptide A long stiff extracellular structure in which 3 bonds polypeptides (α-chains) each 1000 AA in Results from denaturing agents: length are wound around one another in a o Heat, organic solvents, mechanical triple helix mixing, strong acids or bases, Stabilized by hydrogen bonds detergents, ions of heavy metals (e.g., At least 28 distinct types made up of over 30 lead, mercury) distinct polypeptide chains have been May be reversible, but most proteins remain identified in human tissues permanently disordered Most common form is type I collagen Rich in glycine and proline Note that denaturation does not affect a protein’s o X: proline (facilitates kinking) primary structure. o Y: hydroxyproline or hydroxylysine Formed in fibroblasts (or in the osteoblasts GLOBULAR PROTEINS of bone and chondroblasts of cartilage) HEMOGLOBIN Synthesis of Collagen: Heme protein found exclusively in red blood 1. Synthesis of preprocollagen in the rough cells endoplasmic reticulum, and cleavage of Functions: the signal (pre) sequence o Transport of O2 from the lungs to 2. Hydroxylation of proline and lysine capillaries residues, which requires vitamin C o Transport of CO2 from tissues to the 3. Addition of galactose and glucose to lungs hydroxylsine Exists in 2 configurations 4. Formation of triple helix o T (taut) form: low oxygen affinity 5. Secretion of procollagen from the cell into o R (relaxed) form: high oxygen affinity the extracellular matrix, cleaved to form (300x) collagen Hemoglobin binds up to 4 molecules of O2 with 6. Cross-linking of fibers increasing affinity (positive cooperativity) TYPES OF COLLAGEN: Majority of oxygen is transported in the blood through hemoglobin. In contrast, majority of carbon monoxide is transported as dissolved bicarbonate anion. Note that carbohyxhemoglobin refers to carbon monoxide bound to hemoglobin, while carbaminohemoglobin refers to carbon dioxide bound to hemoglobin. MNENOMIC FOR TYPES OF COLLAGEN MYOGLOBIN Type One is in bONE and tendONE. Type Two is in Car TWOlage. Heme protein present in heart and skeletal Type Three has THREEticulin. muscle Type Four is under the FLOOR (FOUR), Functions: o Reservoir of oxygen o Oxygen carrier that increases the rate of ELASTIN transport of O2 within the muscle cell Connective tissue protein with rubber-like Consists of a single polypeptide chain properties, responsible for extensibility and Following massive crush injury, myoglobin elastic recoil in tissues released from damaged muscle fibers colors the Found in tissues where elastic recoil is urine dark red (myoglobinuria) needed: Myoglobin can be detected in plasma following o lungs, large arteries, elastic ligaments, a myocardial infarction vocal cords, ligamentum flavum Rich in proline and lysine, but contains little Because myoglobin only has one polypeptide hydroxyproline and no hydroxylysine chain, it only has a tertiary structure (not quaternary).  Precursor tropoelastin is deposited into an irregular fibrillin scaffold cross-linked by desmosine INTERACTIONS THAT HOLD SUBUNITS TOGETHER: 1. Hydrophobic interactions 2. Electrostatic interactions 3. Hydrogen bonds 4. Interpolypeptide disulfide bonds Hydrophobic interactions are the principal forces that hold the subunits together. Electrostatic forces contribute to the proper alignment of the subunits. DENATURATION OF PROTEINS occurs when a protein loses its native secondary, tertiary and/or quaternary structure; there is cleavage of noncovalent bonds. always correlated with the loss of a protein’s function. DENATURING AGENTS: A. Physical agents - extremes of pH and temperature - high pressure - ultraviolet light - ultrasound B. Chemical agents - organic solvents – acids, alkali, urea, guanidine - detergents CHEMICAL ALTERATIONS: - Decrease in solubility – most visible effect in globular proteins - Many chemical groups which were inactive become exposed and more readily detectable PHYSICAL ALTERATIONS: - increased viscosity - decreased rate of diffusion - increased levorotation - cannot be crystallized BIOLOGICAL ALTERATIONS: - increased digestibility - enzymatic or hormonal activity is destroyed - antibody functions are altered