Exam 3 Content - Biochem

catabolism

chemical reactions that breakdown complex molecules into simpler units to capture energy/harvest high energy electrons to transport to carriers; oxidizing reactions

anabolism

chemical reactions that buildup smaller molecules into more complex molecules, consuming energy/taking high energy electrons from carriers; reducing reactions

thermodynamic driving force

highly favorable chemical reactions that can be coupled to intrinsically non-favorable reactions to make the overall pathway favorable

ATP hydrolysis

ATP + H2O → ADP + Pi

An extremely favorable chemical reaction that is essentially irreversible, with a deltaGo ~ -31 kJ/mol

phosphoryl transport potential

the ability for a phosphate-group containing molecule to favorably donate a phosphate to ADP to form ATP; must have a higher deltaGo than ATP hydrolysis to be favorable

carbon fuel oxidation

an extremely favorable process that powers the pumping of H+ against its concentration gradient across the inner mitochondrial membrane

NADH, FADH2

reduced forms of high energy electron carriers that contain the high energy electron pair

energy extraction from food

1) large food molecules broken down into smaller units

2) convert smaller units into acetyl CoA

3) fully oxidize acetyl CoA in the CAC and capture e- with carriers to take to ETC for oxidative phosphorylation

activated carriers

high energy, complex molecules that carry other useful groups for use in metabolic pathways; examples include ATP, NADH/FADH2, NADPH, and CoA

NADH

an example of a high energy electron, nucleotide based carrier; is much larger than the e- pair that it carries; tightly holds electrons in an N-containing ring to eventually transfer to O2 via the ETC to synthesize ATP

CoA

a carbon chain carrier that can be bound to an acyl or acetyl group via its S atom in a thioester bond

acetyl CoA hydrolysis

acetyl CoA + H2O ←→ acetate + CoA + H+

a favorable reaction that has a deltaGo comparable to ATP hydrolysis

acyl group

a carbonyl connected to a carbon chain

allosteric regulation

a common method of metabolic regulation that is similar to noncompetitive inhibition; uses key metabolites to act as “information molecules” that enzymes can sense to activate or deactivate a particular process; adjusts rate of deltaGo < 0 reactions

lipid metabolism

the process of adding/removing 2 carbons at a time (1 acetyl group) to build up or breakdown lipids

fatty acid

a molecule made up of a lipid/hydrocarbon tail with a carboxyl group (pKa ~3-4); carries a -1 charge at physiological pH because of carboxyl group; hydrocarbon tail is highly reduced such that large amounts of energy can be harvested per gram

fatty acyl

an acyl group (ketone + hydrocarbon tail) bonded to a CoA group with a thioester bond

triacylglycerol

a molecule with 3 fatty acids esterified on to a glycerol backbone; removes the -1 charge of the fatty acids to make the whole molecule electrically neutral; ideal for energy storage because it is neutral, highly reduced, and anhydrous

adipocytes

cells that use ~90% of their volume for an organelle dedicated to lipid storage

fatty acid degradation

occurs in the mitochondria

1) Mobilization → TAG is hydrolyzed with with lipase (in process lipolysis) to release glycerol and 3 FAs

2) Activation and transport → FAs are activated by linkage to CoA and transported to the mitochondria

3) Breakdown → repeated oxidation (removing 2C/1 acetyl group at a time) + subsequent processing of acetyl CoA to capture useful electron pairs with carriers

lipolysis

the process of breaking down TAGs into glycerol and FAs with lipases; activated by signaling from catabolic hormones

beta oxidation

the process of breaking down the activated fatty acyl CoA chain at the beta carbon (relative to the CoA group)

1) Oxidation removes two H’s at the alpha and beta carbon to form a new C=C, e- pair captured by FADH2

2) Hydration across double bond forms -OH at beta-C

3) Oxidation at beta-C turns -OH into keto group (=O), e- pair captured by NADH

4) Cleavage of C-chain at the beta-C releases acetyl CoA and fatty acyl CoA (requires new CoA group) that is 2C shorter

one round releases one acetyl CoA, one fatty acyl CoA (2C shorter), FADH2, NADH

fatty acid synthesis

a metabolically regulated process that adds 2 carbon atoms at a time to a fatty acid chain via a series of reactions

requires an activated malonyl CoA (rather than acetyl CoA) to make the reaction thermodynamically favorable

takes place in the cytoplasm, uses NADPH as an electron carrier to reduce the carbon chain

condensation, reduction, dehydration, reduction

acetyl CoA carboxylase

an enzyme that adds a carboxyl group to acetyl CoA to form malonyl CoA, an activated reactant with a higher G value that can then participate in fatty acid synthesis; catalyzes the “committed” step of FA synthesis

NADPH

an electron carrier used in anabolic reactions; has an additional phosphate group that is easily recognizable, aiding in regulation of catabolic vs. anabolic reactions

mitochondrial matrix

the innermost part of the mitochondria that is enclosed by the inner mitochondrial membrane; the inner membrane has many folds which is important to allow for many metabolic processes to take place

low ATP concentration

a signal for enzyme to catabolize or increase rate of catabolic reactions

increased citrate concentration

a signal for enzymes to decrease the reaction velocity of step 1 of the CAC (decrease catabolism); signals that step 2 enzymes are already saturated with citrate and can not take in any more citrate

increased insulin concentration

signals a “fed” state and promotes triacylglycerol storage

increased palmitoyl CoA concentration

signals fatty acid abundance and acts as a “master signal” to inhibit acetyl CoA carboxylase

amphipathic

a quality of lipids that make them both hydrophilic and hydrophobic

membrane fluidity

requires a good ratio of saturated to unsaturated fatty acids and tails that vary in length; incorporation of cholesterol can also disrupt close packing

phospholipids

the most abundant lipid in membranes made of a phosphate + alcohol head group; phosphate group will always carry a -1 charge, but overall charge can vary depending on alcohol group; typically has a glycerol scaffold and is found in both leaflets of the membrane to provide membrane structure; fatty acid tails esterified to the scaffold

glycolipids

a less abundant type of lipid in the membrane with a head group made of 1+ sugars; has a neutral charge and typically a sphingosine backbone; only found on the outer leaflet for cell surface recognition (sugars display information outside the cell)

sphingosine

an amino alcohol that has its own fatty acid tail

sphingomyelin

a type of lipid with a sphingosine backbone; the second fatty acid tail is attached with a stronger amid linkage that makes it ideal for durability

membrane permeability

small nonpolar molecules move most easily through the membrane with ions not being able to move through the membrane at all

integral membrane proteins

membrane proteins that are completely embedded in the membrane and span the lipid bilayer

peripheral membrane proteins

proteins that are loosely associated with the membrane through the phosphate heads or other integral proteins

stage 1 of glycolysis

the “investment” stage that consumes 2 ATP

1) glucose is phosphorylated (1 ATP) to produce glucose-6-phosphate (phosphorylated at carbon external to ring)

2) G6P is isomerized into the more symmetrical fructose-6-phosphate

3) F6P is phosphorylated (1 ATP) to produce fructose-1,6-bisphosphate

4) F-1,6,-bisphosphate is broken down into two 3-carbon intermediates

gluconeogenesis

glucose synthesis from 3-carbon precursors (pyruvate, glycerol, etc); mainly in the liver

glucose preference

is water soluble and can travel through the bloodstream to be quickly mobilized; useful for quick energy demands

pyruvate

a versatile three carbon intermediate; can be completely oxidized, undergo gluconeogenesis, or fatty acid synthesis; must enter the mitochondrial matrix before processing

phosphofructokinase

enzyme that regulates step 3 of glycolysis, the “control point”; phosphorylates fructose-6-phosphate to produce fructose-1,6-bisphosphate; has a substrate binding site for ATP (with high affinity) and a negative allosteric site with moderate affinity for ATP; positively regulated by F2,6-BP and AMP, negatively regulated by ATP and citrate

stage 2 of glycolysis

the payoff stage of glycolysis that involves synthesizing pyruvate from the two 3-carbon intermediates; releases 2 ATP and 1 NADPH per pyruvate

substrate level phosphorylation

when an enzyme binds ADP and a substrate with a higher phosphoryl transfer potential than ATP to directly synthesize ATP

control points

regulatory points in metabolic pathways that occur at highly favorable (essentially irreversible) steps

fructose-2,6-bisphosphate

a dedicated signaling molecule that is only for reporting hexose abundance

insulin

an anabolic hormone that helps regulate fructose-2,6-bisphosphate

glucagon

a catabolic hormone that helps regulate fructose-2,6-bisphosphate production

anabolic pathways

can not run concurrently with catabolic pathways; do not exist for pathways that product CO2 as a product

gluconeogenesis regulation

a process that synthesizes glucose and is negatively regulated by AMP, ADP, and F-2,6-BP, and is positively regulated by acetyl CoA

citric acid cycle

the process of completely oxidizing acetyl CoA into two CO2; captures 4 electron pairs as 3 NADH and 1 FADH2; powers ATP synthesis with oxidative phosphorylation

electron transport chain

pumps hydrogen ions from the matrix to the intermembrane space, made favorable by movement of electrons down to oxygen; generates a proton gradient

ATP synthase

an enzyme that contains a physical spinning motor to couple the movement of hydrogen ions down their gradient to the synthesis of ATP from ADP and Pi

oxidative phosphorylation

the primary method of recycling ATP; the process of electrons flowing from NADH (or FADH2) to O2 coupled to formation of H+ gradient, H+ flow through ATP synthase to phosphorylate ADP; deltaGo ~ -220 kJ/mol (for NADH oxidation to O2)

pyruvate dehydrogenase complex

the protein complex that process pyruvate into acetyl CoA

1) Oxidation to harvest e- pair (NADH)

2) Oxidative decarboxylation (release CO2)

3) Link to CoA to form acetyl CoA

oxaloacetate regeneration

step 8 of the citric acid cycle with a highly positive deltaGo; due to it NOT being an oxidative decarboxylation step; immediate consumption of oxaloacetate by step 1 makes it thermodynamically favorable

NADH build up

a regulatory signal to inhibit the citric acid cycle; signifies that the electron transport chain is at capacity and can not work any faster

citric acid cycle control

activated by “low energy” (low ATP, high ADP/AMP), F-2,6-BP; inhibited by NADH build up, citrate build up (feedback inhibition); also influenced by catabolic and anabolic hormones

pyruvate dehydrogenase regulation

increased activity when energy is depleted (need more acetyl CoA for CAC), or substrate is abundant (increased pyruvate); decrease activity when energy is abundant, product is abundant, or NADH is abundant

cellular respiration

the used of carbon fuel molecule to harvest electrons that travel through multiple favorable steps to pump H+ to form an H+ gradient, to use flow of H+ through ATP synthase to phosphorylate ADP

electron transport chain

a series of protein complexes in the inner mitochondrial membrane that electrons from carriers travel through, releasing energy that is used to pump H+ out of the matrix; also includes carriers (Q molecule and protein cytochrome C)

NADH enters at Complex I

FADH2 enters at Complex II (which generates FADH2 as part of CAC)

e- move from Complex I/II → Q → Complex III → cytochrome C → Complex IV

Complexes I, III, and IV are H+ pumps

mitochondria organization

highly folded inner membrane increases surface area for oxidative phosphorylation; outer membrane permeable, inner membrane highly selective; folds create local regions of high [H+], which is where ATP synthase is located

ATP synthase

a protein with an integral portion (containing spinning turbine where H+ travels) and peripheral portion to phosphorylate ADP to form ATP