53: Glycolysis and Hemolysis Flashcards
How does the glucose in blood enter cells?
GLUT transporters by facilitated diffusion
Glut 2
liver
Glut 1 & 3
neurons and brain
Glut 1
erythrocytes
Glut 4
adipose tissue and muscle
responsive to insulin
numbers elevated when blood glucose level high
Glucokinase
phosphorylates glucose to G6P
in liver has high Km for glucose
present in β cells of pancreas
Hexokinase
phosphorylates glucose to G6P
other tissues/RBC, has low Km for glucose
Glycolysis
brain and erythrocytes
generate ATP w/ or w/o oxygen
w/ or w/o mitochondria
glycolytic enzymes in cytosol
Stage 1: Energy Investment
two irreversible phosphorylation reactions requiring 2 ATP
PFK-1: 2nd reaction, most important regulated step (allosteric regulated)
Stage 2: 6C to 3C intermediates
Aldolase cleaves F1,6BP into G3P and DHAP
Aldolase A - muscle
Aldolase B - liver
Triosephosphate isomerase DHAP into G3P
Stage 3: Energy Generation
G3PD forms NADH+
1,3 BPG (high energy compound) forms ATP without ETC by Phosphyglycerate kinase
Phosphoenolpyruvate (high energy compound) forms ATP without ETC by pyruvate kinase (irreversible)
Pyruvate fate
Aerobic: Pyruvate to Acetyl CoA to TCA cycle
Anaerobic: Lactate to liver via Cori cycle
Pyruvate: High NADH levels
reaction toward lactate formation
Intense exercise
high NADH/NAD ratio
pyruvate converted to lactate
high lactate in muscle, drop in pH –> cramps
lactate in muscle and RBC diffuse to liver for gluconeogenesis
Cardiac muscle
low NADH/NAD ratio
lactate -> pyruvate -> acetyl CoA -> TCA cycle
hypoxia: lactate formation (MI)
Arsenate
inhibits glyceraldehyde 3-phosphate dehydrogenase
G3P –> 1,3BPG
Fluoride
inhibits enolase
2 phosphoglyerate –> phosphoenolpyruvate
2,3 BPG
anaerobic glycolysis
binds to β-globin chains and helps unload oxygen to tissues
formation increased at high altitudes
Pyruvate kinase deficiency
decreased ATP generation
ATP maintains electrolyte conc. (Na+/K+ ATPase)
2nd most common form of hemolytic anemia
Defect in glycolytic pathway
Pyruvate Kinase or Hexokinase deficiency
RBC lysis
Lactic acidosis
metabolic acidosis
pH low, HCO3- decreased, PCO2 decreased
increased pyruvate to lactate (high NADH/NAD ratio)
anaerobic metabolism in tissues b/c of cardiac failure
Lactate not transported to liver
Pyruvate Dehydrogenase Deficiency
inherited Leigh disease
PFK-1
allosterically regulated enzyme
Fructose-6-Phosphate to Fructose-1,6-Bisphosphate
Inhibits glycolysis
ATP (muscle)
Stimulates glycolysis
AMP (muscle)
Hexokinase deficiency
Hemolytic anemia