Flashcards in Glycolysis and Pyruvate Dehydrogenase Deck (26):
Why do the GLUT 1 and 3 have high affinity for glucose? How is the Km and velocity in normal concentration of glucose?
Ensure glucose entry even in hypoglycemia
Low Km (1mM)
Vmax at Normal [glc] - basal uptake
What senses the glucose level for insulin release?
GLUT 2 and glucokinase in B cells pancreas
Why is GLUT 4 transporter insulin-dependent? Where are those GLUT?
- Induce exocytosis of cytoplasmic vesicles containing GLUT 4 ▶️ fusion with cell membrane
- muscle, adipose tissue
What other stimuli cause translocation of GLUT 4? What mechanism involve?
Exercise - independent of insulin
Involves a 5' AMP-activated kinase
In term of kinetics what would be the effect of insulin in transport and "behavior" of GLUT 4?
⬆️ Vmax - work as an activator (more numbers of transporters)
How the mucosal cells uptake the glucose? Wha type of transport is it?
Why ischemia leads in coagulation necrosis?
⬇️ O2 ▶️ ⬆️ NADH (somebody has to oxidate it, mitochondria couldn't) ▶️ LDH ▶️ ⬆️ lactic acid ▶️ acidosis ▶️ denature and precipitate proteins ▶️ coagulation necrosis
What is the only mean to produce ATP in anaerobic tissue?
Substrate-level phosphorylation (no O2 dependent) - ADP is directly phosphorylated to ATP using a high-energy intermediate
What enzymes in glycolysis can make substrate-level phosphorylation and get ATP directly? What intermediates substrates uses?
3-phosphoglycerate kinase ▶️ 1,3-Biphosphoglycerate
Pyruvate kinase ▶️ PEP
What is the cause of permanent neonatal type 1 Diabetes? What is the mechanism?
Near-complete deficiency of glucokinase activity
Can't sense glucose correctly with GLUT 2 ▶️ no insulin releasing
What can cause a mutation in glucokinase that increase and decrease its Km?
- ⬆️ Km ▶️ (decrease affinity for Glc) ▶️ maturity-onset diabetes of the young (MODY)
- ⬇️ Km ▶️ (increasing affinity for Glc) ▶️ hyperinsulinemia and hypoglycemia
What is the difference between hexokinase and glucokinase?
- the tissue (most tissues vs hepatocyte and B-islet cell)
- Km (⬇️ hexokinase, ⬆️ glucokinase)
- regulation (glucose 6P [-] hexokinase, insulin [+] liver glucokinase)
What inhibit and activate the PFK-1? What is the role of insulin and glucagon?
- ATP and Citrate (-) by energy production, "active krebs"
- AMP (+) by Exercise
- insulin ▶️ (+) PFK-2 (dephosphorylate) ▶️ ⬆️ fructose 2,6 BP (+)
- glucagon (-) PFK-2 (phosphorylate) ▶️ ⬇️ fructose 2,6 BP
For what can be used dihydroacetone-P (DHAP)?
- by glycerol-3P DH ▶️ glycerol-3P:
*TGL synthesis in adipose and liver
What is the effect of an abnormal elevation of 2,3 BPG?
- ⬇️ even more the affinity of Hb for O2
*oxygen dissociation curve for HbA - shift the curve far right
*HbA hot fully saturated in lungs
Second most common genetic deficiency cause of hemolytic anemia, what is the first?
- pyruvate kinase deficiency
- first: glucose 6-P DH deficiency
Characteristic of pyruvate kinase deficiency
Hemolytic anemia, ⬆️ 2,3 BPG, No Heinz bodies
What causes hemolysis in pyruvate kinase deficiency?
- ⬇️ ATP ▶️ RBC lose biconcave shape ▶️ spleen destruction
- ⬇️ ion pumping by Na/K ATPase ▶️ loss ion balance ▶️ osmotic fragility ▶️ swelling and lysis
What is mechanism that produces cataracts (hallmark) in galactosemia?
- ⬆️ Gal in blood ▶️ aldose reductase in lens of eye ▶️ ⬆️ galactitiol ▶️ osmotic damage
Why galactosemia by gal 1P uridyltransferase deficiency is more severe than galactokinase deficiency (only cataracts)?
- accumulation of Gal 1-P in brain, liver, other tissues
Other symptoms of galactosemia (meanly Gal 1-P uridyltransferase deficiency)
- Jaundice and hyperbilirrubinemia (not resolve with phototherapy)
- 3 day old
- vomiting and diarrhea
- Severe bacterial infections (E. coli sepsis)
- thrive, lethargy, hypotonia, mental retardation
*newborn screening heel pick test
Cause and symptoms of hereditary fructose intolerance
- aldolase B deficiency ▶️ accumulation fructose 1-P in liver and renal proximal tubules
- lethargy, liver damage, Renal proximal tubule defect (resemble Fanconi syndrome), hyperbilirrubinemia, hyperuricemia, hypoglycemia, vomiting
"Let's Live in Rest, two hygh, sweat low"
Based on the role of Pyruvate dehydrogenase, what is the consequence of thiamine deficiency? Common cause of it?
*Alcoholics ▶️ ⬇️ thiamine absorption
*wenicke-korsakoff syndrome (peripheral neuropathy and psychosis)
- Cerebral hemorrhage, Ophtalmoplegia, Memory loss, Ataxia, psychosis (confabulation) and Nystagmus ▶️ "COMA On brain and eyes"
What is "wet beri beri"? Why does it occur?
*Congestive Heart Failure by Chronic prolonged thiamine deficiency (complication)
*⬇️ ATP, ⬆️ accumulate ketoacids in cardiac muscle
What mainly regulates the PDH, in what pathway is it important?
- prevents consumption of Pyruvate when is needed ▶️ to gluconeogenic pathway