Metabolism: Basic Concepts Flashcards
What is the essence of metabolism?
conversion via biochemical reactions
What are two basic purposes of metabolism?
1) Bioenergestics: extract energy from energy fuels or collect energy from environment
2) Biosynthesis: gather small molecules (building blocks) from environment and energy fuels and synthesize macromolecules and their building blocks
Metabolic pathways are connected steps of biochemical reactions. The ____ of a previous step will serve as the ____ in the next step.
The PRODUCT(S) of a previous step will serve as the REACTANT(S) in the next step.
Metabolic pathways are interconnected. This means two things:
1) a metabolite have different fates (at junctions)
2) metabolic pathways are interdependent: alteration of a pathway also impacts on the whole metabolism
What are the two major categories of metabolic pathways?
1) catabolic pathways (jointly called catabolism)
2) anabolic pathways (jointly called anabolism)
What are catabolic pathways?
reactions/pathways that breakdown macromolecules (particularly energy fuels) into smaller units and extract energy
What are anabolic pathways?
reactions/pathways that utilize energy and small molecules to synthesize more complex biomolecules
What are some examples of catabolic pathways?
glycolysis, glycogenolysis
lipolysis, fatty acid oxidation
proteolysis, amino acid catabolism
What are some examples of anabolic pathways?
gluconeogenesis, glycogenesis
fatty acid, synthesis, lipogenesis
amino acid synthesis, protein synthesis
What is the basic concept #1 relating to oxidation?
oxidation of energy fuels provides energy for metabolism
How does the oxidation of biomolecules release energy?
1) oxidation of carbon atoms from its reduced forms (as in C-H, C-C, C-O bonds) releases energy
2) organic biomolecules are enriched for reduced carbons (C-H, C-C, C-O bonds)
3) the conversion of C-H, C-C, C-O bonds in biomolecules to C=O bonds (CO2) releases energy and drives metabolism
The oxidation of biomolecules in catabolism takes place in a stepwise manner. What are these three stages? What is the central theme of catabolism?
Stage 1: breakdown of large molecules into smaller units (food digestion) THIS STEP CONSUMES ENERGY (ATP) RATHER THAN GENERATING ENERGY
Stage 2: breakdown of small molecules into a few simple units, particularly ACETYL COA. this step generates a small amount of ATP.
Stage 3: complete oxidation of Acetyl CoA generates a large amount of ATP
What is the basic concept #2 relating to energy storage?
energy is stored in different forms in metabolism
What is the universal energy currency? What are its two critical properties?
ATP
1) ATP is a HIGH-ENERGY molecule with two PHOSPHOANHYDRIDE BONDS. When ATP is hydrolyzed, the reaction (HYDROLYSIS REACTION) releases a large amount of energy
2) ATP CAN NOT ONLY RELEASE ENERGY BUT ALSO TRANSFER ITS ENERGY TO OTHER METABOLITES ( the structure of ATP determines that ATP can easily transfer its terminal phosphoryl group to other metabolites–> HIGH PHOSPHORYL-TRANSFER POTENTIAL)
ATP can temporarily store what in other what in the form of what?
ATP can temporarily store energy in other metabolites in the form of phosphoryl transfer potential
Phosphoryl transfer potential can be used to generate what?
to generate ATP
Molecules with phosphoryl-transfer potential that is higher than ATP can generate what and how?
they can readily generate ATP via substrate level phosphorylation
What are some examples of molecules with higher phosphoryl transfer potential higher than ATP?
PEP
1,3-BPG
P-Creatine
What is substrate level phosphorylation?
one of the two means of ATP generation
-it takes energy released from the breaking of a high-energy bond to drive ADP phosphorylation to ATP (the generation of high-energy phosphoanhydride bond between Beta and Lambda phosphate groups)
Metabolism converts energy in five forms. What are these five forms? How do they work?
thermal energy: body temperature
chemical energy: chemical bonds in energy fuels
electromagnetic energy: high-energy electrons in NADH/FADH2
kinetic energy: movement of F1 subunit of ATP synthase
potential energy: proton gradient in mitochondria
In biochemistry, ATP is an activated carrier for what?
for phosphoryl groups (also has high phosphoryl transfer potential)
What is phosphorylation reaction?
the phosphoryl transfer from ATP to a substrate
Phosphorylation reactions are:
1) thermodynamically favorable (ATP has very high phosphoyl transfer potential)
2) kinetically favorable (reactions can be very fast)
What are phosphorylation reactions catalyzed by?
kinases
human genome has more than 520 kinases
Where can the phosphorylation occur?
On a:
-protein
-lipid
-nucleotide
-carbohydrate
The phosphorylation state of a molecule can affect what?
activity
reactivity
ability to bind to other molecules
In a protein, Phosphorylation occurs on hydroxyl groups in amino acid residue side chain. Phosphorylation of proteins is critical in what?
the regulation of metabolism and many other cellular pathways
Phosphorylation alters the confirmation of what?
proteins (enzymes)
Order of amino acid residues in a protein that can be phosphorylated:
Serine > Threonine > Tyrosine & Aspartate
Phosphorylation of these residues causes local conformational changes, which determines what?
the enzyme activities and/or the interactions with other molecules
What is the universal phosphoryl donor/carrier for kinases?
ATP
What are the two electron carriers in catabolism?
NAD+ and FAD
What are NAD+ and FAD?
activated carriers of high energy electrons
How is NAD+ synthesized?
from the pyridine structure from vitamin B3
How is FAD synthesized?
from the flavin structure from vitamin B2
What does NAD+ usually oxidize?
alcohols into aldehydes or ketones
What does FAD usually oxidize?
alkanes into alkenes (saturated to unsaturated fatty acids
What are NAD+ and FAD both activated carriers of high-energy electrons for?
activated carriers of high-energy electrons for energy fuel oxidation
What occurs during energy fuel oxidation (catabolism?
1) the high energy electrons from energy fuels (C-H, C-O bonds) are transferred to NAD+ and FAD
2) NAD+ and FAD go to their reduced forms, NADH and FADH2 each carrying two high energy electrons
3) the electrons then transfer from NADH and FADH2 to other electron carriers and eventually received by molecular oxygen O2
What is dehydrogenase?
the enzymes that catalyze the electron transfer between NAD+/FAD and other molecules
What is an electron carrier in anabolism?
NADP+
What is NADP+?
an activated carrier of electrons for the synthesis of biomolecules
When biomolecules are synthesized, electrons do what?
electrons are transferred from NADPH to smaller building blocks
the building blocks are reduced and the energy from the electrons are stored in form of chemical bonds
NADP+ reduces what?
NAD+ oxidizes what?
NADP+ reduces: aldehydes/ketones into hydrocarbons
NAD+ oxidizes: alcohols into aldehydes or ketones
Enzymes in anabolism specifically recognize what, and why?
specifically recognize NADPH because of the extra phosphate group in the ribose ring
What is Coenzyme A (CoA)?
a carrier for Acyl group
Coenzyme A is an activated carrier of what?
of acyl groups in both fuel oxidation and biosynthesis
CoA- SH (sulfhydryl) is synthesized from what?
vitamin B5
CoA reacts with an acyl group and forms what?
acyl-CoA with a high energy thioester bond
In acyl-CoA, what is energy input required for?
energy input is required for the generation of the thirster bond in Acyl-CoA
What happens when you break the thioester bond in Acyl-CoA?
acyl groups and energy is released
What are three common short-chain acyl CoAs?
Acetyl CoA (2C)
Propionyl CoA (3C)
Butyryl CoA (4C)
The breaking of thioester bonds in acyl-CoAs is thermodynamically:
favorable, which makes acyl-CoAs VERY REACTIVE (hydrolysis)
Short-chain Acyl CoAs can react with what? How?
can react with lysine residues on proteins by transferring the short acyl groups to lysine (acyltransfer)
Besides proteins, short-chain acyl CoAs also react with what?
many metabolites
Short-chain acyl CoAs are critical metabolites for what?
for protein modifications and proper cellular function
Acetylation of p53 protein at lysine (K120) is critical for what?
critical for the function of p53 to induce programmed cell death (apoptosis)
TIP60 prevents p53 deacetylation (removal of acetyl groups) by ___, ensuring____
by HDAC5 and thus ensures apoptosis when DNA is damaged
Inactivation of TIP60 can do what?
can cause cancer as it is a halo insufficient tumor suppressor
What inactivates TIP60?
Human Papillomavirus E6
Why is metabolism constantly changing in humans?
we don’t eat when we sleep so metabolism adjusts at night during this time of fasting
we are very active in the day and eating and exercising so metabolism must adjust to this
What cycle do humans follow?
the circadian cycles
Metabolism can swiftly adapt to what?
physiological changes through their complicated regulationa
In general, what are three rules in metabolic regulation?
1) An anabolic pathway and its corresponding reverse catabolic pathway usually DO NOT take place at the same sub cellular location (compartmentalization)
2) An anabolic pathway and its corresponding reverse catabolic pathway are NOT active at the same time
3) Most metabolic regulations occur at irreversible steps
Which organelles in a cell are locations for compartmentalization?
Mitochondria
Nucleus
Golgi
Endoplasmic reticulum
What are the metabolic enzymes and metabolites separated from others by?
membrane structures in the cell
What factors make a biochemical reaction irreversible?
thermodynamics (reactions w/ considerable Gibbs free energy changes are usually irreversible–large negative values of delta G)
kinetics (lack of catalyzing enzyme make it irreversible)
What are the three principal ways metabolic pathways are regulated?
1) amount of enzyme (relatively slow)
2) availability of substrate
3) catalytic activity of enzyme
The amount of enzymes are regulated how?
by gene expression (transcription, translation)
the slowest means of metabolic regulation BUT important roles in circadian cycle
What is the slowest means of metabolic regulation?
amount of enzymes regulated by gene expression
How is the availability of substrates regulated?
regulated by:
-availability of substrates
-accessibility of substrates
Regulation of enzymatic activities: allosteric mechanisms by metabolites. What is allosteric regulation?
non-covalent binding of metabolites to enzymes (at allosteric regulatory sites) changes the conformation of the enzymes and affects the accessibility/affinity of the active sites to the substrates
Regulation of enzymatic activities: reversible covalent modifications catalyzed by enzymes.
The modification of allosteric sites by the covalent binding of a molecule or chemical group can change the conformation of an enzyme in what two ways?
1) turn a hydrophobic region into a hydrophilic region (the presence of a negative charge in the phosphoryl group in case of phosphorylation)
2) introduce special fitness/hindrance (by the carbon structures in case of acetylation)
Covalent modifications of the allosteric sites are mostly what? Example?
mostly reversible
the phosphorylation can be reversed by phosphatase, acetylation can be reversed by deacetylase
Some metabolites are competitive ____ of metabolic enzymes. Why?
Some metabolites are competitive INHIBITORS of metabolic enzymes BECAUSE they structurally resemble substrates and compete for active sites of the enzymes
Competitive inhibitors have distinct what?
distinct Michaelis-Menten kinetics than noncompetitive inhibitors
Can you tell an inhibitor is a competitive or a non-competitive based on a M-M curve?
YES
an increase of the substrate concentration (to the right side of the curve) can eventually negate the inhibitory effect of a competitive inhibitor, but not for a non-competitive inhibitor
Interpret this chart.
Energy charge reflects the energy status of the cell.
0 = when all adenine nucleotides are AMP
1 = when all adenine nucleotides are ATP
As ATP is generated the rate goes down (when ATP levels are high, the cell does not need to produce as much ATP)
As ATP is utilized the rate goes up (when ATP is used up, ADP and AMP levels increase as more ATP needs to be made)
This balance helps keep homeostasis.
