No, only if energy is needed or not (positive/negative sign)
Most important class of biochemical reactions?
Redox, since oxidation provides most energy for aerobic metabolism. Electrons used in ETC to pump protons and make ATP.
One major role of kidneys with blood?
Regulate blood pH
How do kidneys regulate blood pH?
Remove protons in form of ammonium ion (NH4+) and reabsorb bicarbonate (HCO3-). Low blood pH triggers increase in both of these processes.
What does the gastric proton pump do?
Pumps H+ into gastric lumen to make HCl with Cl- for gastric acid.
What to do to reduce gastric acid secretion? Why?
Inhibit gastric proton pump with omeprazole, etc. Used for ulcers, indigestion, heartburn.
What are side effects of omeprazole?
Decreased HCl in gastric acid causes decreased nutrient absorption (vitamin B12, calcium ions), increased food poisoning sensitivity, reduced efficacy of gastric enzymes (pepsin, gastric amylase, gastric lipase) that digest proteins, carbs, and lipids.
What is allopurinol? Targets what?
Pharmaceutical agent used to treat chronic gout (accumulation of uric acid in synovial fluids, thus joint pain/inflammation). Targets xanthine oxidase - enzyme that converts hypoxanthine to uric acid in purine degradation.
How is allopurinol a suicide inhibitor?
Binds active site of xanthine oxidase, which then converts the allopurinol to its actie metabolite oxypurinol, which binds tight and is slowly released (noncompetitive inhibitor).
What is myasthenia gravis?
Autoimmune disease caused by inhibition of acetylcholine signaling by antibodies that bind to acetylcholine. Muscle weakness, fatigue, can't hold one's gaze.
How can physostigmine treat myasthenia gravis?
Inhibits acetylcholinesterase enzyme via binding and subsequent inactivation. Acetylcholine can't be broken down in synaptic cleft.
How are metalloenzymes inhibited?
Chelating agents bind to and remove metal cofactors from enzyme. EDTA is one such chelating agent.
What are symptoms of lead poisoning?
Abdominal pain, anemia, irritability, headaches, impaired nervous system development and encephalopathy
How do chelating agents treat lead poisoning?
Ex. Ca-EDTA treatment causes lead (higher affinity for EDTA than calcium) to displace calcium and be removed to create Pb-EDTA and excreted in urine. In children, chelating agent succimer is used.
What is Tn-I? How is it related to myocardial infarction?
The inhibitory subunit of troponin (3 subunits total). After a myocardial infarction, one of the 3 isoforms (cTn-I)'s serum levels in the cardiac muscle are elevated. sTn-I is found in skeletal muscle.
What are 6 enzymes whose elevated blood  indicates a certain disease?
What is Fanconi-Bickel syndrome? Symptoms and treatment?
Inherited deficiency of GLUT2 glucose transporter in liver, pancreatic beta cells, and proximal renal tubules. Causes stunted growth, hepatomegaly, and bouts of hypoglycemia between meals but hyperglycemia after a meal. Glucose and galactose not rapidly cleared from circulation after eating. Glucose generated via gluconeogenesis not released. Treatment is small frequent meals and avoid galactose in diet.
How does GLUT2 aid in glucose sensing?
GLUT2 maintains intracellular and extracellular glucose levels ("sensor") in pancreatic beta cells. Increased blood glucose causes glucose to be brought into cells by GLUT2 and metabolized into ATP. Increased ATP causes K+ channels to close --> beta cell depolarization --> voltage-gated Ca2+ channels to open --> calcium influx --> insulin release. Calmodulin and calcium/calmodulin-dependent protein kinase (CamK) increased also for insulin synthesis.
What is a glucose tolerance test?
Test for type 2 diabetes. Oral glucose followed by fasting. Measure plasma glucose before and and at intervals after glucose administration. Resting should be <6.1 mmol/L. After 2 hours, <7.8. Levels >11.1 after 2 hours = diabetes diagnosis.
What is drug-induced lupus erythematosus?
Body metabolizes many drugs via acetylation. People with this have genetic mutations in acetylation reaction enzymes. Longer half-life of drugs = converted to toxic by-products --> antinuclear (antihistone) antibody production. Symptoms are like lupus (muscle/bone pain, rashes, inflammation of lungs and heart, fever, fatigue).
How much protein does a typical 70kg (154 lb) person consume, degrade, and synthesize daily?
100g consumed, 400g degraded and 400g synthesized
Component amino acids broken down to provide energy or create biomolecules. Nitrogen from AA's channeled into urea cycle of liver to be excreted as urea (urine) or sweat.
Free energy change equation for a reaction
∆G = ∆Gº' +RTln([B]/[A])
Equation for standard free energy change
To couple reactions, what is required?
Must share a common intermediate
Why can you calculate total ∆G for coupled reactions?
∆G's are additive
How to get reaction to flow?
Increase reactant or decrease product (Le Chatelier)
Is gibbs free energy indicative of the reaction velocity?
What is diabetic ketoacidosis?
Diabetics cannot burn glucose well, burn FA's instead, creating ketone bodies that release protons to lower pH
Two types of biochemical reactions
Redox and acid-base
All biochemical reactions involve the ___ of electrons, atoms, or groups of atoms
Normal blood pH range
7.37 - 7.43
What is respiratory acidosis?
Blood pH <7.37 due to hypoventilation, i.e. CO2 build-up, so blood pH reaction shifts to make more protons
What is the equation for blood pH regulation?
H2O + CO2 <--> H2CO3 <--> H+ + HCO3-
Strong acid addition (lactate, ketone bodies) or bicarbonate loss (diarrhea, weak kidneys)
Blood pH >7.43 via hyperventilation, decreased CO2, equation shifts
pH > 7.43 via strong base addition (antacid ingestion) or acid loss (vomiting)
Another way to remember relationship between ventilation and proton gain/loss
Hyperventilation is like breathing out protons, while hypoventilation is maintaining protons
Main physiological acids
acetoacetic acid and beta-hydroxybutyric acid
Main physiological bases
bicarbonate and ammonia
pH = pKa + log(conj base/conj acid)
If more conj base than conj acid in blood, what happens to pH?
log(>1) is positive, means pH from H-H equation increases
Main metal ions required by metalloenzymes
Copper, iron, magnesium, selenium, zinc
Ex. protein that needs copper
Cytochrome c oxidase - accepts e's from cytochrome-c in ETC
Ex. protein that needs iron
Hemoglobin (heme group)
Ex. protein that needs magnesium)
ATPases (ATP -> ADP) and kinases (phosphate grp transfer)
Ex. protein that needs zinc
Superoxide dismutase (binds free radical O's)
Heme, NAD+, NADP+
Pepsin optimal pH and location
pH = 2, stomach acid
Trypsin optimal pH and location
pH = 8, duedenum/intestines
How does pancreas raise pH in intestines from that of stomach acid? Why?
Pancreatic juices contain bicarbonate to raise pH for trypsin optimal pH of 8
How is reaction rate related to temperature?
Fastest at optimal temp, slower below and above (heat-induced enzyme denaturation)
What is the catalytic triad?
Asp, His, Ser interaction in chymotrypsin where the H of the serine OH is taken by the Histidine ring, creating a potent alkoxide ion (O-) on the serine for the active site to cleave peptide bonds via hydrolysis
What does peptide hydrolysis by chymotrypsin have to do with covalent and acid-base catalysis?
Histidine acts as a general base catalyst by accepting the proton from serine, creating the alkoxide ion
What is Km and how does it relate to reaction velocity?
Equation in relation to substrate concentration?
Constant [substrate] where v = 1/2 v-max
V = (Vmax[S])/Km + [S])
What does the M-M kinetics graph look like?
Hyperbolic with flat top at v-max and Km at 1/2 v-max
Km is __ proportional to velocity
How do the Km's of glucose transporters in the brain and pancreas differ? Why?
Brain - low Km for constant glucose feed because always needs to be active (Km = 0.1)
Pancreas - high Km for activity only when glucose levels are high after a meal
What are the effects of competitive inhibition on Vmax and Km? Why?
What does the graph look like then?
Vmax is unchanged, while Km is increased. Increasing [S] allows substrate to out-compete inhibitor.
The hyperbolic curve is less steep but plateaus at same vmax.
What are the effects of noncompetitive inhibition on Vmax and Km? Why?
What does the graph look like then?
Vmax lowered, Km unchanged. Increasing [S] will not allow substrate to out-compete inhibitor.
Same steepness with equal Km's, but plateaus at lower vmax.
What are the effects of uncompetitive inhibition on Vmax and Km?
Both lowered since inhibitor only binds to enzyme-substrate complex. Look up why...
Effects of enzyme inactivation on Vmax and Km? Why?
Vmax lowered, Km unchanged. Increasing [S] won't allow substrate to out-compete inhibitor.
What kind of V/[S] kinetics curve do allosteric enzymes create?
Sigmoidal rather than hyperbolic
How do allosteric activators and inhibitors affect the v/[S] kinetics curve?
Activator - shifts curve left
Inhibitor - shifts curve right
What is one allosteric activator that stimulates gluconeogenesis? Where does it come from? How does it relate to my low-carb diet?
Acetyl-CoA, which comes from fatty acid breakdown. So must break down fats to build sugar for energy. If sugar creation is needed (i.e. not consumed), we will break down fats to get the necessary effector molecule.
What are isozymes and how do they relate to diagnosing diseases?
Isozyme - enzymes w/ diff. AA sequence but catalyze same reaction.
Enzymes/proteins have different isozymes that are present in different tissues. If seen in blood, sign of breakdown of that tissue.
What controls the utilization of chemical energy contained in glucose?
What happens when blood glucose levels are low and glycogen stores have been depleted?
Gluconeogenesis to make glucose from pyruvate and other carbon molecules
What 2 types of proteins help new proteins fold correctly?
Chaperons and enzymes
What 3 things help localize and degrade proteins as necessary?
Translocation machinery, proteasomes, and autophagic activities
What are unfolded proteins bound to other unfolded proteins called?
What receptor complexes in mitochondrial membranes recognize preproteins to be brought in and folded?
Tom40 pore (Tom complex) in outer membrane (recognized by Tom20 and Tom22), and Tim23 complex in inner membrane
How is homeostasis regulated at a transcriptional level?
via transcription factors that can promote or repress gene transcription
Post-translational protein modifications are crucial to a proteins what? (5)
Function, regulation, subcellular localization, interaction w/ other molecules, and degradation
Where does post-transcriptional protein modification take place?
on specific sites of certain amino acid residues
5 main post-translational protein modifications
Acylation (acyl group attachment) Glycation (nonenzymatic glucose attachment) Glycosylation (enzymatic sugar attachment) Phosphorylation (phosphate group via ester bond) Ubiquitination (small protein called ubiquitin)
What does ubiquitin mark?
Mark for degradation
2 forms of intracellular protein degradation
Lysosome (engulfed and eaten by enzymes)
Proteasome (fed through subunits and chopped up)
Extracellular protein digestion?
Extracellular proteolytic enzymes secreted as inactive zymogens
Intestinal example of extracellular proteolytic enzyme?
Trypsinogen cleaved into trypsin by enteropeptidase. Then Trypsin can cleave other trypsinogens independently of enteropeptidase.
How do membranes assist with homeostasis?
Controlling substance entry and exit, enclosing toxic material, and allowing food, water, waste exchange
One catabolic mechanism of dysfunctional cellular component degradation and recycling?
Autophagy, where autophagosome engulfs old component, then lysosome fuses with autophagosome to create autolysosome and break down component
Mitochondrial matrix is the site of what 4 things?
Beta-oxidation of fatty acids, TCA cycle, urea cycle, and calcium ion storage
3 ways mitochondria maintains homeostasis
Fusion of healthy with unhealthy to mitigate stress via complementation
Fission into 2 to remove damaged portion w/o losing the mitochondria (or to create a new mitochondria)
Complete elimination via mitophagy
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