biochem Flashcards
major electrolytes in body?
Na +and Cl -are the major electrolytes in the ECF
• K + and phosphates (HPO4 2- ) are the major electrolytes in cells
when does water move out of the cell?
300 is the plasma level
The loss of cellular water can occur in hyperglycemia because the high concentration of glucose increases the osmolality of the blood. - WATER FOLLOWS
When the osmolality of the blood or interstitial fluid is too high, water moves out of the cells.
PH of pure water?
7 - anything under 7 is acidic
Do strong or weak acids disassociate more rapidly
strong - and they dissassociate completely
Ketone bodies?
Organic acids containing carboxylic acid groups (the ketone bodies) are weak acids that dissociate to only a limited extent in water
Acidic drugs are best absorbed where?
Drugs are absorbed in there uncharged forms
most drugs are weak acidic or weak bases
stomach ASPIRIN (stomach pH = 1-2) - vs basic (intestine) MORPHINE 7.9
pH of blood?
7.36 and 7.44, and intracellular pH at approximately 7.1
how is acid excreted from the body?
CO 2in expired air and as ions in the urine, it needs to be buffered in the body fluids.
Acid produced everyday?
Body produces a LOT of acid - must be neutralized - or have a problem - pH will go wacky
Volatile acid:
Carbon dioxide (CO2 ) – major metabolic acid (22,000mmol/day)
• Nonvolatile acids (40-80 mmol/day)
Three types of buffers - first line of defense
A buffer exhibits maximum buffering capacity, when pH=pKa:
bicarb, phosphate, protein
A buffer is usually effective at a pH = pKa ±1 ✮
Major buffer systems in the body:
- Bicarbonate-carbonic acid buffer (ECF buffer)
- The most important buffer of the plasma - Proteins (ICF and plasma RBC) - due to histidine residues Hemoglobin (red blood cells) – due to histidine residues
- Phosphate buffer (ICF and urine buffer)
- Ammonia (urine)
regulating pH - what does respiratory system reg, vs renal?
respiratory - co2,
renal - HCO 3
Buffers - how do they change with pH change?
As the pH of a buffered solution changes from the pKa to 1 pH unit below the pKa , the ratio of [A- ] to HA changes from 1:1 to 1:10. If more hydrogen ions were added, the pH would fall rapidly because relatively little conjugate base remains.
carbonic anhydrase?
This buffer system is more complex than others, because carbonic acid (H2CO3) is formed from dissolved CO 2 which produced in tissues and diffused to plasma).
• The pKa of the bicarbonate buffer is 6.1 (close to the plasma pH of 7.4)
CO dissolves in water by Carbonic anhydrase to form the weak acid, carbonic acid (H2 2 CO 3 )
Carbonic anhydrase
Dissociation
CO 2 + H2 O
H2 CO3
HCO3 −
+
H+
The bicarbonate: carbonic acid ratio in blood at physiological pH is 20:1 and the pKa value is
6.1, both significantly different from the ‘ideal’.
However, two factors contribute in making the bicarbonate: carbonic acid pair effective in blood at physiological pH:
- It is present in high concentrations in blood.
- It is an open system, that can be regulated by two mechanisms: by the excretion of CO 2 via the lungs and by the regulation of the rate of reclamation of HCO 3 − in the r
Shift to the right, left?
Co2 accumulate - shift equilibrium to right
Hemoglobin as a Buffering Agent
Released protons take part in the formation of salt bridges between globin chains of Hb, and lead the change in the conformation of Hb molecule in tissue capillaries.
The most important buffer groups of Hb are histidines. Each globin chain contains 9 histidine.
• 95 % of CO 2 which is released from tissues to plasma is diffused into erythrocytes.
respiration and ph?
when pH falls, respiration increases - washing out the extra CO2
when pH rises - respiration slows, retaining CO2
Renal control of acid-base balance
The kidneys also play a major role in controlling acidbase homeostasis through their ability to recover filtered HCO 3 − and to generate HCO3 − . It is during HCO 3 − generation that H + ions are excreted.
- Bicarbonate recovery
- By this mechanism HCO3− is not lost.
- Bicarbonate generation
phosphate buffer system?
High concentrations of phosphate are prevalent in bone and the intracellular fluid. This is significant in some acidotic states when phosphate can be released from the bones and act as a buffer in the plasma.
ECF - and kidneys - but as there isn’t much phosphate in body, not a very good buffer, even though the pK is ideal (6,8)
normal PH, PCO2, and HCO3 levels?
Normal levels:
– pH: 7.35-7.45 (arterial)
– PCO2 : 35-45 mmHg
– HCO3 - : 22-26 mmol/L
Acidaemia - excess H +in the arterial blood, when the resulting pH is less than 7.35
• Alkalaemia - too few H + , with a pH greater than 7.45
The causes of these disturbances may be due to:
- Respiratory disorders, with a primary change in PCO2 , due to dysfunction of the respiratory system
- Metabolic (non-respiratory disorders), which initially cause changes in the concentration of HCO3 − , due to metabolic or renal disorders
if respiratory problem -
renal system compensates, and vice versa
Metabolic acidosis - HCO3 is down - pH down
causes:
- Increased production of non-volatile acids:
- Diabetic ketoacidosis (increased ketone body production)
- Lactic acidosis (increased lactate production)
- Chronic renal failure (decreased excretion of sulfate, phosphate)
- Increased loss of HCO 3 - (base):
- Diarrhea (increased loss of HCO 3 - rich intestinal secretions)
- Renal tubular acidosis (failure to secrete H + and reabsorb HCO3 - , aldosterone deficiency or impaired response to aldosterone in the distal tubule)
Acute stage: In the acute stage:
– pH is decreased (<7.36)
– PCO 2 is almost normal(<40mmHg)
[HCO3 - ] is decreased (primary abnormality)
Metabolic acidosis - compensation?
Until the cause of acidosis is treated, pH does not come back to normal
In the compensated stage, ✮ (clinically more commonly observed) pH is lower than normal (<7.36) - closer to normal pH, when compared to acute stage
PCO 2 is decreased due to compensatory hyperventilation (<35mmHg)
[HCO 3 ] is decreased (primary abnormality)
breathing - increased rate of respiration (Kussmaul respiration) → Increased washout of CO2 → ↓↓ PCO2 ✮
If the renal system is functioning, the renal system can also compensate to increase H+ excretion, increase the formation of new HCO3-.
metabolic alkalosis - HCO goes up - why?
Causes of metabolic alkalosis:
- Vomiting
- pyloric stenosis resulting in vomiting
- Loss of acidic contents of the stomach, results in relative HCO3- excess.
- Nasogastric suction.
- Excessive consumption of antacids
- Renal loss of H + (Cushing’s disease, bilateral adrenal hyperplasia)
In the acute stage, (clinically, may not be observed)
– pH is increased (greater than 7.44)
– [HCO3 - ] is increased (greater than 25mmol/L) (primary abnormality)
– PCO 2 is almost normal
compensation - metabolic alkalosis?
pH is higher than normal (closer to normal pH, when compared to acute stage) ü[HCO 3 - ] is increased (primary abnormality) üPCO 2 is increased (compensatory mechanism)
Respiratory acidosis - hypoventilation
CO 2is NOT washed out resulting in elevation of PCO 2(primary abnormality)
In the acute stage:
üpH is decreased (lower than 7.36) üPCO 2 is elevated (primary disturbance) üHCO 3 - is almost normal
Why? Clinical causes:
- Drugs that inhibit the respiratory center (opioids)
- Diseases/ injury of the phrenic nerve (supplies diaphragm)
- Lung diseases like chronic obstructive pulmonary disease, fibrosis of the lung, respiratory distress syndrome in premature infants
- Obstruction to the respiratory tract – due to foreign body in trachea
increased arterial PCO 2(hypercapnia), which decreases the [HCO3 − ] / PCO 2 ratio. The underlying problem is due to CO2 retention, as a result of hypoventilation.
compensation - respiratory acidosis
pH is lower than normal (<7.36) - closer to normal pH, when compared to acute stage
PCO2 : Elevated (as the primary defect is still not corrected – respiratory system is still not functioning optimally)
During compensation, the renal system comes to the rescue
- Kidneys excrete more H+ , and generate more HCO3 - , and thus the [HCO3 - ] levels increase
- The excretion of phosphate and ammonia in urine increase
Respiratory alkalosis
increase in rate of respiration → increased washout of CO 2 → ↓↓PCO 2 (primary disturbance)
Causes of hyperventilation
- Anxiety
- Fever
- Hysteria
- Hypoxia (high altitude) stimulates the respiratory center and increases the rate of respiration. When a person stays for a long time at the high altitude, the compensatory mechanisms are active and [HCO3 - ] levels fall
• Mechanical ventilation
✮
In the acute stage:
– pH is increased (<7.44)
– PCO 2 is ↓↓ (<35mmHg)
– [HCO3 - ] is almost normal
compensation respiratory alkalosis
In the compensated phase ✮ :
– pH is higher than normal - closer to normal pH, when compared to acute stage
– PCO2 : Decreased (as the primary defect is still not corrected – respiratory system is still hyperventilating)
– [HCO3 - ]:Decreased(due to renal compensation)
renal system tries to bring the pH back towards normal
• The kidneys do NOT secrete H + into urine
saME - MEtabolic
REverse - REspiratory
Look only at pH and CO2
if pH is UP and co2 is UP - - metabolic alkalosis
if pH is UP and co2 is DN - respiratory alkalosis
if pH is DOWN and co2 is DOWN - - MET Acidosis
if PH is Down and co2 is UP - Respiratory Acidosis
Glycine -
smallest (great for tight helixes, turns
no assymetric carbon atom
peptide bonds
produces molecule of water -
carboxyl group of one amino acid and the amino group of the incoming amino acid combine and release a molecule of water.-
links two consecutivealpha-amino acids from C1 (carbonnumber one) of one alpha-amino acid and N2 (nitrogennumber two) of another along apeptideorproteinchain
What do introns and exons do?
Introns and exons are nucleotide sequences within a gene. Introns are removed by RNA splicing as RNA matures, meaning that they are not expressed in the final messenger RNA (mRNA) product, while exons go on to be covalently bonded to one another in order to create mature mRNA.
polycistronic v monocistronic
prokaryotes - mRNA carries more than one gene
monocistronic - eukaryotes - carries message for only one gene
types of RNA
3 main classes:
Ribosomal RNA – rRNA
Messenger RNA – mRNA
Transfer RNA – tRNA
Other: Small nuclear RNAs – snRNAs MicroRNAs – miRNAs Small interfering RNAs – shRNAs, siRNAs Heterogeneous nuclear RNA – hnRNA
Ribozymes - RNAs with catalytic activity. Ribozymes function during protein synthesis, in RNA processing reactions, and in the regulation of gene expression.
when is mRNA formed?
after processing of heterogeneous nuclear RNA
hnRNA (heterogenous nucleus RNA)
25% make it through
tRNA
clover leaf like structure. The structure is stabilized by hydrogen bonding
carry amino acids to ribosomes and recognizes the genetic code (codon) sequence on an mRNA
tRNA acceptor arm at 3’ - at the OH end -
the 5’ end has the phosphate
CCA can carry amino acids
T arm, D arm, variable arm
. T-arm
contains the TΨC (riboThymidine, pseudouridine, cyTidine) sequence necessary for tRNA-ribosomebinding.T arm Tethers tRNA molecule to ribosome.
4. D-arm
contains Dihydrouridine residues necessary for tRNA recognition by the correct aminoacyl-tRNAsynthetase.D-armDetectsthetRNAbyaminoacyl-tRNAsynthetase
5. Extra arm or Variable arm
Small nuclear RNA - splicing
snRNAs - in nucleus,
splicing nhRNA to create mature mRNA
U1, U2, U5, and U4/U6 particles
snurps are bound to the snRNAs
