Membrane Active Transport

Membrane Transport Examples: Facilitative Diffusion Ionophore Maltoporins GLUT1 transprter Aquaporin Selective ion channel for potassium (K-channels) Active Transport Primary (1°) Na+/K+ ABC Secondary (2°) Na+/Glc Bicarb/Cl– Lactose/H+ Group Translocation Bacterial phosphotransferase system (PTS) Membrane Transport Active Transport Membrane Transport Examples of Active Transport Two Types Membrane Transport One of the best and most important examples of Active Transport (primary): The sodium–potassium (Na+–K+) pump is primary active transport. Found in all animal cells. The pump is an integral membrane glycoprotein (an antiporter). Membrane Transport Sodium– potassium (Na+– K+) pump a2b2g pentamer Membrane Transport Sodium– potassium (Na+–K+) pump Due to b subunit Membrane Transport Sodium– potassium (Na+– K+) pump Calls secondary active transport “facilitative diffusion” https://youtu.be/IKoKjCL27mA Khan academy Membrane Transport Sodium– potassium (Na+– K+) pump Molecular Dynamics video https://youtu.be/1zvnsrKQ2Jg Membrane Transport ABC Transporters Use ATP Hydrolysis to Drive Transport of Substrates OUT Membrane Transport ABC Transporters Use ATP Hydrolysis to Drive Transport of Substrates IN Membrane Transport Failure of ABC-Transporters Can Lead to Human Disease • Mutations in the human CFTR transporter (an ABC-type transporter-like channel for chloride ions)(cystic fibrosis transmembrane-conductance regulator) result in the human disease cystic fibrosis. • Single-amino-acid mutations can render the protein misfolded and/or unable to transport chloride ions, resulting in an imbalance of water across the membrane. Regulated Facilitative Diffusion • Phosphorylated by PKA • Puts it in ATP cycle Dr. Kornberg’s ”Giraffe” story Membrane Transport Examples of Secondary Active Transport Bicarbonate Transporter is an Antiporter Maintains the electrochemical potential across the membrane Membrane Transport The bacterial Lactose Transporter is an Symporter Uses the power of a proton gradient across the plasma membrane Membrane Transport Efficient Import of Glucose uses Multiple Glucose Transporters • A Na+-glucose symporter and a glucose uniporter operate on opposite sides of epithelial cells to facilitate movement of glucose from the intestine to the blood. • Uses the Na/K gradient set up by “the pump.” Membrane Transport TABLE 11-7a ✓ Transport Systems Described Elsewhere in This Text Transport system and location Figure Role IP3-gated Ca2+ channel of ER 12-11 Allows signaling via changes in cytosolic [Ca2+] Glucose transporter of animal cell plasma membrane; regulated by insulin 12-20 Increases capacity of muscle and adipose tissue to take up excess glucose from blood Voltage-gated Na+ channel of neuron 12-29 Creates action potentials in neuronal signal transmission 17-3 Imports fatty acids for fuel 17-6 Imports fatty acids into matrix for β oxidation 19-16 Act as energy-conserving mechanism in oxidative phosphorylation, converting electron flow into proton gradient 19-25, 2020a, 20-24 Interconverts energy of proton gradient and ATP during oxidative phosphorylation and photophosphorylation 19-30 Imports substrate ADP for oxidative phosphorylation and exports product ATP 19-30 Supplies Pi for oxidative phosphorylation 19-31 Shuttles reducing equivalents (as malate) from matrix to cytosol 19-31 Completes shuttling begun by malate-α- ketoglutarate shuttle ✓ Fatty acid transporter of myocyte plasma membrane ✓ Acyl-carnitine/carnitine transporter of mitochondrial inner membrane Complex I, III, and IV proton transporters of mitochondrial ✓ inner membrane FoF1 ATPase/ATP synthase of mitochondrial inner ✓ membrane, chloroplast thylakoid, and bacterial plasma membrane nucleotide antiporter of mitochondrial inner ✓ Adenine membrane ✓ P -H symporter of mitochondrial inner membrane transporter of mitochondrial inner ✓ Malate-α-ketoglutarate membrane Glutamate-aspartate transporter of mitochondrial inner ✓ membrane i + Membrane Transport TABLE 11-7b Transport Systems Described Elsewhere in This Text Transport system and location Figure Role ✓ Uncoupling protein UCP1, a proton pore of mitochondrial inner membrane 19-36, 2335 Allows dissipation of proton gradient in mitochondria as means of thermogenesis and/or disposal of excess fuel ✓ Cytochrome bf complex, a proton transporter of chloroplast thylakoid 20-19 Acts as proton pump, driven by electron flow through the Z scheme; source of proton gradient for photosynthetic ATP synthesis ✓ Bacterorhodopsin, a light-driven proton pump 20-27 Is light-driven source of proton gradient for ATP synthesis in halophilic bacterium Pi-triose phosphate antiporter of chloroplast inner membrane 20-42, 2043 Exports photosynthetic product from stroma; imports Pi for ATP synthesis Citrate transporter of mitochondrial inner membrane 21-10 Provides cytosolic citrate as source of acetyl-CoA for lipid synthesis Pyruvate transporter of mitochondrial inner membrane 21-10 Is part of mechanism for shuttling citrate from matrix to cytosol LDL receptor in animal cell plasma membrane 21-41 Imports, by receptor-mediated endocytosis, lipid-carrying particles Protein translocase of ER 27-40 Transports into ER proteins destined for plasma membrane, secretion, or organelles Nuclear pore protein translocase 27-44a Shuttles proteins between nucleus and cytoplasm Bacterial protein transporter 27-46 Exports secreted proteins through plasma membrane ✓ ✓ ✓ Membrane Transport Summary We learned that: •Membrane proteins play an important functional role in the transport of solutes across the membrane •Transport is mediated or non-mediated. •In mediated transport, there is a facilitative diffusion mechanism or an active transport mechanism •Active transport is either primary or secondary •Primary active transport of solutes across membranes requires ATP •The most important, and one of the best examples of primary active transport, is the Na/K ATPase. •Secondary active transport but can be accomplished in many ways, but uses the potential energy established by primary active transport or pre-established concentration gradients CATABOLISM Glycogen-o-lysis Glyco-lysis Pyruvate Oxidation Krebs' Cycle First, let’s discuss how crucial glucose is for cellular metabolism Phosphorylation Oxidative CATABOLISM Glucose Importance: • Glucose is an excellent fuel. – yields good amount of energy upon oxidation • −2840 kJ/mol glucose (–678 kcal/mol) – can be efficiently stored in the polymeric form – Many organisms and tissues can meet their energy needs on glucose only. • Glucose is a versatile biochemical precursor. – Many organisms can use glucose to generate: • • • • • all the amino acids membrane lipids nucleotides in DNA and RNA cofactors needed for the metabolism of EVERYTHING IOW, EVERYTHING!! CATABOLISM Glucose Utilization: • Storage – can be stored in the polymeric form (starch, glycogen) – used for long-term energy needs • Energy production – generates energy via oxidation of glucose – short-term energy needs • Production of NADPH and pentoses – generates NADPH for use in relieving oxidative stress and synthesizing fatty acids, amino acids, etc. (anabolism) – generates pentose phosphates for use in DNA/RNA biosynthesis • Structural carbohydrate production – used for generation of alternate carbohydrates used in cell walls of bacteria, fungi, and plants CATABOLISM Glucose Utilization: NADPH / Four Major Fates of Glucose What if you need glucose for cellular metabolism and energy? Glucose is Stored for Later Use as Glycogen (animals) or Starch (plants) • Glycogen/starch are branched polymers of α(1à4)-linked glucose with α(1à6) linkages (glycogen every 8-12 glucose units; starch every 24-30 glucose units). • Glycogen storage occurs mainly in the liver and muscle. Digestion • Starch storage occurs mainly in the leaves and seeds. maltose maltase glucose Digestion versus intra-cellular utilization (isomaltase) Glycogenolysis is performed mainly by Glycogen Phosphorylase intra-cellular utilization 1 1 a-D 2 3 2 3 Glycogenolysis is performed mainly by Glycogen Phosphorylase Glycogenolysis must deal with Branch Points in Glycogen • Glycogen phosphorylase works on nonreducing ends until it reaches four residues from an (a1® 6) branch point. • Debranching enzyme has two activities; a glycosyltransferase and a glycosidase – Debranching enzyme transfers a block of three residues to the nonreducing end of the chain. – Debranching enzyme hydrolyzes the single remaining (a1®6)-linked glucose, which becomes a free glucose unit (i.e., NOT glucose 1-phosphate). • The Glc enters glycolysis, but the Glc 1-P must be converted to the glycolytic intermediate Glc 6-P first. • How? Glycogenolysis must deal with Branch Points in Glycogen • Glycogen phosphorylase works on nonreducing ends until it reaches four residues from an (a1® 6) branch point. • Debranching enzyme has two activities; a glycosyltransferase and a glycosidase – Debranching enzyme transfers a block of three residues to the nonreducing end of the chain. – Debranching enzyme hydrolyzes the single remaining (a1®6)-linked glucose, which becomes a free glucose unit (i.e., NOT glucose 1-phosphate). • The Glc enters glycolysis, but the Glc 1-P must be converted to the glycolytic intermediate Glc 6-P first. • How?