Chpt 15 Flashcards
Metabolism
all reactions found in cells
2 types of metabolism
1) Catabolism-breakdown
- breakdown of large organic molecules (proteins, lipids, carbohydrates) into smaller molecules (CO2, H2O, lactate)
- Releases Energy which is captured in a usable form as ATP, NADH, NADPH, FADH2 or lost as heat or increase in entropy
2) Anabolism-synthesis
- assembly of smaller precursor molecules into larger more complex molecules (Lipids, polysaccharides, proteins, nucleic acids)
- requires energy
Catabolism
Breakdown and release of Energy
Stage 1:
-complex macromolecules broken down into smaller units. -No free energy trapped.
starch-> monosaccharides
protein-> amino acids
triacylglycerols-> glyercols and fatty acids
Stage 2:
- simple molecules are catabolized to a few molecules that can be oxidized to CO2 and H2O.
- some energy trapped as ATP
Stage 3:
- contains: citric acid cycle, electron transport, and oxidative phosphorylation
- oxidize acetyl CoA to CO2 and H2O
- Majority of energy trapped as ATP
ATP
Adenosine Triphosphate
-principle donor of free energy in biological systems
“Energy Currency of the Cell”
-in vivo nucleotides usually exist in a complex with divalent cations (Mg2+ or Mn2+)
Hydrolysis of ATP
Addition of water to cleave peptide bonds
- cleave of 2 phosphoanhydride (phosphodiester bonds) yields free energy (Exergonic)
- forms orthophosphate (Pi) or pyrophosphate (PPi)
- orthophosphate is stabilized by resonance
Phosphoryl-Transfer Potential
Measure of how readily an organic molecule will transfer a phosphate group
-determined by measuring delta G^o of hydrolysis of phosphate group
What molecules have a higher phosphoryl-transfer potential than ATP? And Why is this good?
- Phosphoenolpyruvate
- 1,3-bisphosphoglycerate
- Creatine Phosphate
-These molecules can transfer a phosphate group to ADP to form ATP during metabolism (regenerates ATP)
Why does ATP have such a higher Phosphoryl-Transfer Potential?
1) Resonance Stabilization
- Pi (orthophosphate) and ADP are more stable than gamma phosphate of ATP
2) Electrostatic Repulsion
- at ph7, ATP carries about four negative charges which repel each other.
- Hydrolysis of ATP to ADP + Pi reduces this repulsion
3) Stabilization due to hydration
- water can bind to (solvate) ADP + Pi more efficiently than ATP
ATP-ADP Cycle
High turn over Adenylate Pool by motion, active transport, biosynthesis, signal amplification
- Human adults have 100gATP/ADP/AMP
- Adult values for rate of use:
a) Resting= 40,000g/24 hours
b) Strenuous exercise (running) = 500g/min or 60,000g/2hrs
Oxidation of organic molecules (glucose and fatty acids) is used to regenerate ATP from ADP and Pi
- Glycolysis
- pyruvate oxidation
- Kreb’s cycle
- electron transport chain
Source of ATP during exercise
- Initially the pool of existing high energy phosphate molecules provide ATP or quick regeneration of ATP by creatine phosphate (SECONDS)
- Then an increase in the rate of aerobic or anaerobic metabolism (oxidation of glucose and fatty acids) regenerate ATP from ADP and Pi
How is most ATP generated?
Most ATP is generated from ion gradients (usually H+) across a membrane
1) Oxidative phosphorylation to create ion gradient
- burning of organic molecules to create an ion gradient to synthesize ATP
1\2) chemiosmotic coupling t ouse proton gradient
-Use of proton gradient by ATP synthase (complex V) to synthesize ATP
NAD+
Nicotinamide Adenine Dinucleotide (oxidized form-NAD+)
- coenzyme
- Niacin is vitamin precursor to NAD+
- deficiency-pellagra resulting in dermatitis, depression, diarrhea
Function-electron carrier
- oxidation of fuel molecules in synthesis of ATP
- H, 2e-, H+
NADP+
Nicotinamide adenine dinucleotide phosphate
- coenzyme
- Niacin is vitamin precursor to NADP+
- Deficiency-pellegra resulting in dermatitis, depression, diarrhea
Function:
- electron carrier
- in reductive biosynthesis
- hydride ion and proton (H + 2e-)
FAD
Flavin adenine dinucleotide (FAD/FADH2)
- coenzyme
- Vitamin-riboflavin (Vitamin B2)
- deficiency-cheliosis and angular stomatitis (lesions of the mouth) dermatitis
Function: electron carrier
-oxidation of fuel molecules in synthesis of ATP
CoA
- coenzyme
- vitamin-pentothenate is a vitamin precursor
- deficiency-hypertension
Function: carries acyl units (8-12 C’s) and linked to SH by thioester bond
-a=acetylation
Vitamins
organic molecules that are needed in small amounts in the diet of some higher animals
- many (not all) vitamins are metabolized into coenzymes
- vitamin deficiency leads to disease state
Enzyme Classes
OTH LiL-T; 2-CNP, 4-CNS; 6CONS
EC1-oxidoreductase-catalyzes oxidation/reduction reactions
EC2- transferase-catalyzes the transfer of C, N, or P containing groups
EC3- Hydrolase- catalyzes the cleavage of bonds by addition of water
EC4- Lyase- catalyzes the cleavage of C-C, C-S, and some C-S bonds
EC5-Isomerase- catalyzes the racemization of optical and geometric isomers
EC6-Ligase-catalyzes the formation of C, O, N, or S bonds coupled to Hydrolysis of high energy Phosphate
EC7-Translocase- catalyzes the transfer of a molecule from one side of membrane to the other side of membrane
Common Enzyme Names
Kim-DA; tii-o_
Kinase (transferase)-transfer of a phosphate group from one molecule(Gamma phosphate of ATP) to another molecule
Isomerase (isomerase)- converts molecule to another isomer. Rearranges atoms in the molecule without gain or lose of atoms
Mutase (isomerase)- shift of phosphate from one carbon to another carbon in the same molecule
Dehydrogenase-require NAD+ and FAD+; oxidation/reduction reaction
Aldolase (lyase)- cleaves c-c bonds (Reverse Aldol condensation reaction)
Metabolic States
1) Fed
- occurs during and just after (3-4 hours) a meal
2) Fasting
- occurs HOURS (6-8 hours) after eating
3) Starvation
- occurs after extended fasting (DAYS)
Regulation of Metabolic Pathways
- compartmentalization
- hormonal control
- non-hormonal control
- Flux of key metabolic intermediates
- specialized roles of organs/tissues
Comparmentation
REGULATION OF METABOLIC PATHWAYS
1) Cytosol
- Glycolysis
- Pentose phosphate pathway
- Fatty acid synthesis
2) Mitochondrial Matrix
- Citric acid cycle
- Oxidative phosphorylation
- Oxidation of fatty acids
- Ketone bodies formed
3) BOTH
- Gluconeogenesis
- Urea cycle
Hormone Control
1) Insulin
- signals the fed state, the availability of glucose in the blood
2) Glucagon and Epinephrine
- When there is low levels of glucose in the blood signals the fasting state
3) Epinephrine
- signals stressful states when mobilization of fuel is required
Non-hormonal Control
1) Allosteric control
- activity of key enzymes is modulated by the levels of metabolites which act as activators or inhibitors
- key enzyme=rate-limiting; committed step in pathway
a) Glycolysis
b) Gluconeogenesis
c) Fatty acid synthesis
2) Respiratory Control
- flux of the pathway matches the need of the cell for ATP
a) citric acid cycle
b) Fatty acid synthesis
c) oxidative phosphorylation
3) Substrate Availability
- pentose phosphate pathway
- urea cycle
4) covalent moderation.
- hormone triggered reaction cascades result in covalent modification
a) glycogenesis
b) glycogenolysis
Flux of Key Metabolic Intermediates
- Glucose 6-phosphate
- Pyruvate
- Acetyl CoA
Glucose 6-phosphate
KEY METABOLIC INTERMEDIATES
- Glucose from Gluconeogenesis
- Glucose 1-phosphate used in glycogen synthesis
- Pyruvate via glycolysis
- Ribose 5 phosphate for nucleotide synthesis via pentose phosphate pathway
Pyruvate
- Oxaloacetate metabolized via citric acid cycle
- Actyl CoA via oxidative, decarboxylation (pyruvate dehydrogenase)
- Alanine via transamination
- Lactate in muscle tissue
Acetyl CoA
1) Oxidized to carbon dioxide in citric acid cycle
- decarboxylation of pyruvate
- degradation of fatty acid
2) Fatty acids synthesis
3) 3-hydroxy-3-methylglutaryl CoA
- ketone bodies
- cholesterol
Specialized roles of Organs/ Tissues
Tissue dependent metabolism
- All metabolic pathways are not present in all cells and tissue
- Metabolic profiles of the major tissues vary depending upon the metabolic state of the body
a) Liver
b) skeletal muscle
c) Heart muscle
d) Adipose
e) Brain
Liver
SPECIALIZED ROLES
1) maintenance of Blood glucose levels
- Fed State- takes up excess glucose and stores it as glycogen or converts it to fatty acids
- Fasting state- exports glucose derived from glycogen AND gluconeogenesis
2) Fatty acid synthesis
3) Ketone body synthesis- during fasting state
4) Synthesis of plasma lipoprotein
Skeletal Muscle
- maintains stores of glycogen=source of glucose for energy during exertion
- resting muscles prefer fatty acids as fuel
- Muscle protein may also be used as fuel
Heart Muscle
contains NO fuel reserves
-must be continuously supplied with fuel from blood
Adipose Tissue
Primary function is storage of metabolic fuel in the form of triacylglycerol
- Fed State-synthesizes triacylglycerols from glycerol and fatty acids
- Fasting State- triacylglycerols are converted to glycerol and fatty acids
Brain
Uses Glucose as exclusive fuel source
- Fed State- glucose
- Fasting State- adapts to use of ketone bodies
Contains essentially no fuel reserves and must be continuously supplied with fuel from blood
