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Name the three irreversible steps of glycolysis:
Steps 1, 3, and 10
What might deficiency of triose phosphate isomerase result in?
severe and often lethal hemolytic anemia and neurodegeneration
Name the committed step of glycolysis:
Step 3; fructose-6-phosphate is converted to fructose-1,6-bisphosphate via phosphofructokinase (PFK)
Define fermentation and name the two specific types:
anabolic pathways that shift electrons from one organic compound to another; alcoholic fermentation and lactic acid fermentation
Which form of fermentation applies to mammals?
lactic acid fermentation
Name the substrate, enzyme, and products of Alcohol/Ethanol Fermentation:
pyruvate → pyruvate dehydrogenase → acetaldehyde → alcohol dehydrogenase → ethanol
Name the substrate, enzyme, and products of Lactic Acid Fermentation:
pyruvate → lactate dehydrogenase → lactate
What is the ultimate electron donor for fermentation?
glyceraldehyde-3-phosphate
What is the ultimate electron acceptor for lactic acid fermentation?
pyruvate
What is the ultimate electron acceptor for alcohol/ethanol fermentation?
acetaldehyde
Why is fermentation crucial in the context of glycolysis?
regeneration of NAD+ which is required for continuing the process of glycolysis
How are fructose and galactose converted into glycolytic intermediates?
galactose enters pathway as glucose-6-phosphate
fructose enters pathway as fructose-6-phosphate in most tissues BUT IN THE LIVER enters after being metabolized to GAP via fructose-1-phosphate pathway
Explain the steps of fructose-1-pathway:
fructose → fructokinase → fructose-1-phosphate
fructose-1-phosphate → fructose-1-phosphate aldolase → glyceraldehyde & DHAP
glyceraldehyde → triose kinase → GAP
Clinical Insight: What does excessive fructose consumption lead to, and what causes the complications?
Leads to fatty liver, type 2 diabetes, and obesity; this is due to steps 1-4 being skipped in glycolysis and PFK is bypassed so there’s now excessive acetyl CoA that becomes converted to fat
Define and name potential control sites:
enzymes of irreversible steps of glycolysis; includes hexokinase, PFK, and pyruvate kinase
How does glycolysis differ in the muscles vs. the liver?
in muscles, it provides ATP for contractions; primarily regulated by energy charge of cell but in the liver, glycolysis regulates blood glucose levels
Explain regulation of glycolysis in muscles:
hexokinase: inhibited by glucose-6-phosphate (feedback inhibition)
PFK: inhibited by ATP (lowers affinity for substrate); low pH levels so as not to denature
pyruvate kinase: inhibited by ATP, stimulated by fructose-1,6-bisphosphate
Explain regulation of glycolysis in the liver:
hexokinase: inhibited by glucose-6-phosphate
PFK: inhibited by citrate, activated by fructose-2,6-bisphosphate
pyruvate kinase: inhibited by ATP and alanine, stimulated by fructose-1,6-bisphosphate
What enzyme is primarily responsible for phosphorylating glucose in the liver?
glucokinase (has a low affinity for glucose and is only active when blood glucose levels are high but has high kcat for rapid conversion upon binding)
What are glucose transporters?
transporters that facilitate movement of glucose across the cell membrane
Differentiate between the glucose transporters:
GLUT 1 & 3: found in all mammalian tissues, responsible for basal glucose uptake
GLUT 2: found in liver and beta pancreatic cells, regulates insulin/removes excess blood sugar
GLUT 4: found in muscle and adipose tissue, glucose is only supplied here if the rest of the body’s is good, regulates muscle plasma
GLUT 5: found in the small intestine, actually a fructose transporter
To what is insulin secreted in response to?
high blood glucose levels; glucose enters beta cells via GLUT 2 and is metabolized from pyruvate to CO2 and H2O, increase in ATP closes K+ channels/opens Ca2+ channels → influx of Ca2+ ions stimulates insulin release