Amino-acid catabolysis makes energy {amino-acid oxidation}. Liver mitochondria have amino-acid oxidation. Protein-hormone, purine, pyrimidine, vitamin, and porphyrin metabolism involves amino-acid oxidation. Transamination, to make alpha-ketoacid, or deamination, through oxidation by NAD+ to make carbohydrate, removes amino group. Oxidation removes amino acid side chains. Oxidized amino acids become pyruvate, acetyl-CoA, alpha-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate, for use in TCA cycle.
After release through membranes, membrane-protein complex {calcium pump} restores calcium ions to inside membrane.
Protein chains can have cross connections {cross-linking, protein}|. Two nearby cysteines, which form a spontaneous disulfide bond, can have strong cross-linking. Protein side chains can form hydrogen bonds with oxygens on other amino acids, such as glycine, cysteine, tyrosine, serine, threonine, asparagine, and glutamine.
Proteins above 37 C can lose three-dimensional structure {denaturation, protein}|. If protein has less than 100 amino acids, folding is subcritical after denaturation. If protein has more than 100 amino acids, folding is critical after denaturation.
Proteins can catalyze reactions {enzymatic reaction}|.
types
Enzymes can catalyze hydrogen-ion interactions. They can catalyze anion and cation formation. They can catalyze chelation. They can catalyze charge-transfer coupling. They can catalyze organic-acid formation and breakdown. They can catalyze proton abstractions. They can catalyze Schiff-base reactions.
They can catalyze configuration inversion.
They can catalyze phosphate transfer. They can catalyze pyrophosphate incorporation. Adenylate cyclase can catalyze cAMP-mediated reactions. They {guanylate cyclase} can catalyze cGMP-mediated reactions. They can catalyze transfers.
They can catalyze oxidation. They can catalyze reduction.
They can catalyze metal-bridge formation. They can catalyze metal binding.
They can catalyze acetylation. They can catalyze acylation.
They can catalyze free-radical reactions.
They can catalyze ring breaking and forming.
They metabolize amines, amides, aldehydes, histidines, imidazoles, ketones, nitroxides, oxides, serines, thiols, and thiol esters. They metabolize lipoproteins, carbohydrates, membranes, ion channels, enzyme proteins, lipids, and nucleic acids.
process
Enzymatic reactions can involve active-site directed agents, induced fit, steric effects, and molecular vibrations.
process: reversible
In enzyme-catalyzed chemical reaction, substrate and enzyme quickly and reversibly bind together to make transition state {enzyme-substrate complex}. The reversible reaction has forward and backward reaction rates {Michaelis-Menten rate equation, enzymatic reaction}.
process: irreversible
Transition state slowly and irreversibly separates to reform enzyme and make product. The irreversible reaction has only forward reaction rate.
process: overall
Reaction first part reaches equilibrium quickly, and intermediate concentration quickly becomes constant {steady state, equilibrium}. At steady state, intermediate concentration change over time is zero, free-enzyme concentration is much less than substrate concentration, and intermediate concentration equals total enzyme concentration.
d[ES]/dt = 0 = f1*[E]*[S] - b1*[ES] - f2*[ES]. [E] = [ET] - [ES]. [E] << [S], so [ES] = [ET]. [ES] is enzyme-substrate-complex concentration. [ET] is total-enzyme concentration. [E] is enzyme concentration. f1 is reversible-reaction forward rate. b1 is reversible-reaction backward rate. f2 is irreversible-reaction forward rate.
process: rate
Substrate depletion rate equals product creation rate: product amount divided by time in seconds. Rate is reaction velocity. Rate depends on forward rate, of making product from intermediate, times intermediate concentration.
Reaction rate can be constant {constitutive reaction rate}. Reaction rate can depend on another-molecule concentration {induced reaction rate}.
Product formation rate depends on maximum possible rate, substrate concentration, and forward and back reaction rate constants.
Maximum velocity depends on enzyme concentration and rate constant. Maximum rate {maximum velocity} {Vmax} equals forward reaction rate times total enzyme concentration.
Rate constant for whole Michaelis-Menten equation depends on all three rates: Km = (b1 + f2) / f1. Reaction velocity v depends on rate constant Km, substrate concentration S, and maximum velocity Vmax: v = (Vmax * [S]) / (Km + [S]).
After formation, proteins spontaneously rotate around single bonds, under electric forces, to make three-dimensional structures {protein folding}|.
process: forces
Amino-acid side chains have polarity. Amino acids can be more polarized, dissolve in water, and tend to be at protein surface. Electric forces are greatest at protein surface, where water interacts with amino-acid side chains. Protein ends polarize and are always at protein surface.
Amino acids can be non-polar and tend to be in protein interior. Protein middle has no water, and side chains there interact among themselves.
process: time
It takes 0.2 second to fold protein.
process: misfolding
One-third of proteins misfold {misfolding, protein}. Rotenone pesticide increases misfolding.
structure
In protein structure, all torques equal zero, and all angular accelerations equal zero. Peptide bonds have no rotation. Typically, all amino acids contribute to structure.
structure: globular
Protein typically becomes globular, because amino-acid chain folds back on itself. Globular proteins have 3.5 to 7.5 loops, with 16 to 24 amino acids each. Loop almost touches ends. Loop goes in same direction as alpha helix coil. Loop follows right-hand rule, with loop going around fingers and thumb in forward-motion direction along sequence.
structure: peptide bond
Peptide bond has N[H2]-Calpha[HR]-Ccarboxy[O]-N[H]-Calpha[HR]-Ccarboxy[O] (2 is subscript).
Bond lengths are the following. C-C for sp^3 = 0.1524 nanometers. C-H for sp^3 = 0.1090 nanometers. C-S = 0.1810 nanometers. S-S = 0.2036 nanometers. C-O peptide bond = 0.123 nanometers. N-H peptide bond = 0.100 nm. Calpha-N = 0.146 nanometers. Calpha-Csidechain = 0.153 nanometers. Calpha-Hsidechain = 0.100 nanometers. Calpha-Ccarboxy = 0.152 nanometers. C-N peptide bond = 0.132 nanometers. Ccarboxy-Cnextalpha = 0.243 nanometers. N-Cnextcarboxy = 0.246 nanometers. Calpha-Nnext = 0.241 nanometers. Ccarboxy-Cnextcarboxy = 0.372 nanometers. N-Nnext = 0.368 nanometers. Calpha-Cnextalpha = 0.381 nanometer.
Bond angles in degrees are the following. C-C-C for sp^3 = 113.0, C-C-H for sp^3 = 109.3, H-C-H for sp^3 = 107.2, C-S-C = 100.4, and C-S-S = 104.5.
Distance between alpha carbons can be 0.381 nanometers {beta sheet, protein}, 0.250 nanometers {alpha helix, protein}, 0.090 nanometers {beta turn, protein}, or random {random coil, protein}.
Protein structure descriptions can use phi angle around N-Calpha axis and psi angle around Calpha-C axis, at all Calphas. One angle has highest probability.
Right-handed alpha helix has phi angle = -57 degrees and psi angle = -47 degrees. Range can be -180 to +180 degrees. Normal range is -180 to +60 degrees. -120 degrees is normal. For proline, angle is always 0 or 110 degrees.
Beta sheet has phi angle -120 and psi angle +120. Range can be -180 to +180 degrees. Normal range is -60 to +120 degrees. Normal is 0 degrees.
technique
To study protein folding, place start position for first amino acid nonexistent alpha carbon at 0,0,0. Pick phi angle. Make new k-axis vector be N-Calpha bond. New i-axis direction is from k-axis line to Ccarboxy. j axis is cross product of k with i. Pick psi angle. Make k-axis vector be Calpha-Ccarboxy bond. New i axis is direction from bond to previous N. j axis is cross product of k with i.
Translate polar coordinates to Cartesian coordinates as necessary. Use many known structures to get actual side-chain coordinates from actual values. Use these to find conditional probabilities for amino acids and nearest, second nearest, and so on, amino acid, to make large table. Do not use alpha helix, beta sheet, or beta turn for values. Just find best parameter set and number.
Transition state slowly and irreversibly separates to reform enzyme and make product {Michaelis-Menten rate equation, enzyme}. The irreversible reaction has only forward reaction rate.
Amide bonds {peptide bond}| can form between amino-acid carboxyl groups and amino-acid amino groups. Peptide bonds resonate, are planar, have no rotation, and have hydrogen in trans configuration to oxygen. Peptide bonds do not allow branching.
Trypsin in stomach acid normally cleaves proteins, using water. If body water is low, trypsin ligates amino acids, forming water {plastein reaction}.
Cell-membrane proteins {sodium-potassium pump} can use one-third of all ATP, keep cell volume constant, make membrane excitability possible, and drive amino-acid and sugar active transport. If sodium is present, ATPase phosphorylates. Conformational change carries sodium ion from cell inside to outside, and potassium ion from outside to cell inside, against concentration gradients. Digitalis affects sodium-potassium pumps.
5-Chemistry-Biochemistry-Protein
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Date Modified: 2022.0225