Exam 3 Flashcards
How can regulatory enzymes regulate pathways?
Allosteric modulators
Reversible covalent modification
Bind separate regulatory proteins
Removal of segments by proteolytic cleavage (irreversible)
What happens when a positive modulatory binds?
Binding of the positive (stimulatory) modulator (M) causes a conformational change rendering the catalytic subunit active and capable of binding the substrate (S) with higher affinity. On dissociation of the modulator from the regulatory subunit, the enzyme reverts to its inactive or less active form.
What does ATP inhibit?
ATP inhibits the commitment steps of glycolysis
How are covalent modifications linked to regulatory enzymes?
by a separate enzyme
What is the difference between protein kinase and protein phosphates?
Protein kinases transfer a phosphoryl group from ATP to a Ser, Thr, or Tyr residue in an enzyme or other protein substrates.
Protein phosphatase removes the phosphoryl group as Pi.
How are zymogens activated?
Zymogens are activated by irreversible covalent modification
How is enzyme activity modulated?
The total activity of an enzyme can be changed by altering the number of its molecules in the cell, or its effective activity in a subcellular compartment, or by modulating the activity of existing molecules, or by regulatory proteins
What are common points of regulation?
Reactions far from equilibrium are common points of regulation. To maintain steady state all enzymes operate at the same rate
What happens with a 10% increase in the concentration of ATP or AMP?
A 10% decrease in [ATP] can greatly affect the activity of ATP by utilizing enzymes and leads to a dramatic increase in [AMP].
AMP can be a more potent allosteric regulator.
What are the factors that increase AMP?
Reduced nutrient supply and Increased exercise
What increases and decreases AMPK
AMPK is activated by elevated [AMP] or decreased [ATP], by exercise, by the sympathetic nervous system (SNS), or by peptide hormones produced in adipose tissue
What happens when AMPK is activated?
When activated, AMPK phosphorylates target proteins and shifts metabolism in extrahepatic tissues to the use of fatty acids as a fuel; and triggers gluconeogenesis in the liver to provide glucose for the brain. In the hypothalamus, AMPK stimulates feeding behavior to provide more dietary fuel.
Why is glycogen a better storage molecule than glucose?
Glycogen uses less water which makes it better to be stored than glucose
How are glucose residues removed from glycogen?
by glycogen phosphorylase which uses phosphates to lyse bonds – it cleaves the glycosidic bond to make glucose-1-phosphate, and the glycogen molecule is one molecule shorter giving a G6P to run into glycolysis
How do we deal with the branch points in glycogen?
Glycogen phosphorylase works on non-reducing ends until it reaches four residues from an (a1- 6) branch point
Debranching enzyme transfers a block of three residues to the non-reducing end of the chain and leaves the single remaining (a1-6)–linked glucose
What is the reaction of phosphoglucomutase?
The reaction begins with the enzyme phosphorylated on a Ser residue. In step 1, the enzyme donates its phosphoryl group to glucose 1-phosphate, producing glucose 1,6-bisphosphate.
In step 2, the phosphoryl group at C-1 of glucose 1,6-bisphosphate is transferred back to the enzyme, reforming the phosphoenzyme and producing glucose 6-phosphate.
What must happen to blood glucose in glycogen synthesis?
Blood glucose must be:
phosphorylated
labeled with UDP
added to glycogen
What is the role of UDP-glucose?
it is used to add UDP to glucose to form the substrate for GS
Why doesn’t the UDP-glucose mechanism run in reverse?
This enzyme would rather take pyrophosphate + sugar nucleotide and make this product, but can’t because Inorganic pyrophosphatase breaks down phosphate very fast so there will be no pyrophosphate
What does Pyrophosphate ketalase bind to?
Mg2+ and Calcium
What does GS do?
A glycogen chain is elongated by glycogen synthase. The enzyme transfers the glucose residue of UDP-glucose to the nonreducing end of a glycogen branch to make a new (α1-4) linkage, it doesn’t branch.
What is the role of the glycogen branching enzyme?
The glycogen-branching enzyme (also called amylo (1-4) to (1-6) transglycosylase forms a new branch point during glycogen synthesis.
What is glycogenin?
Glycogenin is a stagnant glycogen synthase. It attaches glucose to its tyrosine until it gets outside of its active site and can no longer attach any more glucose; Glycogen can only add to a non-reducing end sticking out somewhere At the core of every glycogen molecule is a glycogenin
How is glycogen synthesis controlled?
Insulin-signaling pathway: increases glucose import into muscle
stimulates the activity of muscle hexokinase
activates glycogen synthase
What is cellular respiration?
Process in which cells consume O2 and produce CO2
Provides more energy (ATP) from glucose than glycolysis
Also captures energy stored in lipids and amino acids
what are the 3 steps of celluar respiration?
- acetyl CoA production - via oxidation of FA, glucose and AA
- acetyl CoA oxidation - generate NADH, FADH2, and 1 GTP
- electron transfer and oxidative phosphorylation -electrons carried by NADH and FADH2 are funneled into a chain of mitochondrial—the respiratory chain—ultimately reducing O2 to H2O. This electron flow drives the production of ATP
Where are the 3 stages of Cellular respiration localized?
Glycolysis occurs in the cytoplasm.
Citric acid cycle occurs in the mitochondrial matrix (Except succinate dehydrogenase, which is located in the inner membrane)
Oxidative phosphorylation occurs in the inner membrane.
What is the mechanism of PDH complex?
In step 1 pyruvate reacts with the bound thiamine pyrophosphate (TPP) of pyruvate dehydrogenase (E1), undergoing decarboxylation to the hydroxyethyl derivative. Pyruvate dehydrogenase also carries the transfer of two electrons and the acetyl group from TPP to the oxidized form of the lipoyllysyl group of the core enzyme, dihydrolipoyl transacetylase (E2), to form the acetyl thioester of the reduced lipoyl group.
Step 3 is a transesterification in which the —SH group of CoA replaces the —SH group of E2 to yield acetyl-CoA and the fully reduced (dithiol) form of the lipoyl group.
In step 4 dihydrolipoyl dehydrogenase (E3) promotes the transfer of two hydrogen atoms from the reduced lipoyl groups of E2 to the FAD prosthetic group of E3, restoring the oxidized form of the lipoyllysyl group of E2.
In step 5 the reduced FADH2 of E3 transfers a hydride ion to NAD+, forming NADH. The enzyme complex is now ready for another catalytic cycle.
What is the mechanism for citrate synthase?
Take AcoA and bind to ooa and it involves an induced fit. Ooa has to bind and there’s a confirmation change to an induced fit and then the enzyme becomes active and we can attach the AcoA and we can then hydrolyze off the thioester to cleave off Coenzyme A leaving citrate.
for some reason, we create isocitrate instead of citrate via aconitase enzyme
What is the rate limiting step of the CAC?
Citrate synthase which is the condensation of acetyl-CoA and oxaloacetate; The only reaction with C-C bond formation
Activity largely depends on [oxaloacetate].
What is the mechanism of isocitrate DH?
the substrate, isocitrate, loses one carbon by oxidative decarboxylation by e’ withdrawal by adjacent carbonyl and Mn2+, and reduction of NAD and end up with a-ketogluturate.
What is the mechanism of a-ketoglutarate DH complex?
A-ketogluturate is oxidized to succinyl co-a and we reduce another NAD. This energy from this bond is sufficient b/c its almost a substrate level phosphorylation. A-ketoglu DH complex works the same way as the PDH complex except we bind a-ketogutrate through its carbonyl and it’s a 4c not 2c
What are the 5 cofactors of a-ketogluturate DH and PDH complex?
thiamine pyrophosphate, coenzyme A, lipoate, FAD, and NAD+
What is the mechanism of Succinyl-coA Synthetase?
In step 1 a phosphoryl group replaces the CoA of succinyl-CoA bound to the enzyme, forming a high-energy acyl phosphate.
In step 2 the succinyl phosphate donates its phosphoryl group to a His residue of the enzyme, forming a high-energy phosphohistidyl enzyme.
In step 3 the phosphoryl group is transferred from the His residue to the terminal phosphate of GDP (or ADP), forming GTP (or ATP).
What is the mechanism of Succinate DH?
the oxidation of succinate (an alkane/single bond) to fumarate (alkene/double bond)
What is the mechanism of fumarase?
we hydrolyze across the double bond of fumarate to make l-malate
What is the mechanism of malate DH
We oxidize L-malate (an alcohol) to OOA (a ketone). although it is unfavorable OOA is being pulled so fast to make citrate that it never has the chance to run the reaction backwards to malate
What is net in one turn of the CAC?
At each turn of the cycle, three NADH, one FADH2, one CoA (from ACoA), one GTP (or ATP), and two CO2 are released in oxidative decarboxylation reactions
What is the mechanism of biotin?
The cofactor biotin is covalently attached to the enzyme through an amide linkage to the ε-amino group of a Lys residue, forming a biotinylenzyme.
The reaction occurs in two phases, which occur at two different sites in the enzyme: At catalytic site 1, bicarbonate ion is converted to CO2 at the expense of ATP. Then CO2 reacts with biotin, forming carboxybiotinyl-enzyme.
The long arm composed of biotin and the Lys side chain to which it is attached then carry the CO2 of carboxybiotinylenzyme to catalytic site 2 on the enzyme surface, where CO2 is released and reacts with the pyruvate, forming oxaloacetate and regenerating the biotinyl-enzyme.
What cancers occur when we are low on oxygen?
Fumarase; cant take fumarate to malatate - Tumor of smooth muscle and kidneys
Succinate dehydrogenase leads to build up succinate - Tumors of adrenal glands due to increase production of adrenalin.
What are the biological functions of lipids?
Storage of energy
Insulation from environment
Water repellant
Buoyancy control and acoustics in marine mammals
What is hydrogenation?
Hydrogenation is taking all the double bonds and saturating them to make saturated fatty acids, and in the process, the cis were all flipped to be trans
What is the solubility and MP of FA?
Solubility - decreases as the chain length increases, and increase with the number of double bonds
Melting Point - decreases as the chain length decreases, and decreases as the number of double bonds increases
What is the difference in formation of saturated and unsaturated FA?
Saturated is very ridged and line up perfectly in a straight line, whereas unsaturated create kinks and disorder
It takes less thermal energy to disrupt disordered packing of unsaturated fatty acids: unsaturated cis fatty acids have a lower melting point
What is trans FA?
Trans fatty acids can pack more regularly and show higher melting points than cis forms
Consuming trans fats increases the risk of cardiovascular disease
What is the advantage of fats over polysaccharides?
Fatty acids carry more energy per carbon because they are more reduced and carry less water per gram because they are nonpolar
Glucose and glycogen are for short-term energy needs, quick delivery whereas Fats are for long-term (months) energy needs, good storage, slow delivery
What are waxes?
Waxes are esters of long-chain saturated and unsaturated fatty acids with long-chain alcohols
Insoluble and have high melting points
Waterproofing of feathers in birds, Used by people in lotions, ointments, and polishes
What composes the Head groups of structural lipids?
Head groups are charged with phosphates which are hydrophilic
What are the 5 types of structural lipids?
- Glycerophospholipids - Hydrophobic region = 2 fatty acids joined to glycerol
- Galactolipids and Sulfolipids - 2 fatty acids joined to glycerol (NO phosphate)
- Archaebacterial tetraether lipids - 2 long alkyl chains- ether linked to glycerol at both ends
- Sphingolipids - One fatty acid joined to a fatty amine
- Sterols - Rigid system of 4 fused hydrocarbon rings
What is the difference between phospho and glycolipids?
In phospholipids the polar head group is joined through a phosphodiester, whereas glycolipids have a direct glycosidic linkage between the head-group sugar and the backbone glycerol.
What are the characteristics of glycerphosopholipid?
Primary constituents of cell membranes
Two fatty acids form ester linkages with the first and second hydroxyl groups of L-glycerol-3-phosphate
Head group is charged at physiological pH
What is a phosphatidylcholine?
a glycerophospholipid that is the major component of most eukaryotic cell membranes (not seen in bacteria)
