Biochem Flashcards
Products of the reaction- hydrolysis of ATP to ADP
Phosphate group donor and acceptor in other metabolic pathways
Hydrogen ion donor in other metabolic pathways
Energy for work
Purpose of ATP hydrolysis
Muscle contraction
ATP hydrolysis causes conformational change in myosin head of muscle filaments
Slides actin filaments
Active transport
ATP hydrolysis enables conformational change of ion channels
Allows ions to be sequestered in compartments against their concentration gradients
Example: Na+-K+-ATPase
Thermogenesis
What is glycolysis
Glucose is oxidised in the cytosol of the cell
It can be aerobic or anaerobic
It is regulated by ATP and AMP and by insulin and glucagon
Rate of glycolysis limited by activity of the enzyme phosphofructokinase
A precursor to fatty acid biosynthesis
What is phosphofructokinase
A precursor to fatty acid biosynthesis - Limits rate of glycolysis
Overview of glycolysis
Preparative phase:
- Glucose +2ATP = fructose-1,6-bisphosphate
ATP generating phase:
fructose-1,6-bisphosphate –>2 triose phosphates– 2NADP—2ATP—2ATP—>Pyruvate
phosphofructokinase-1 Catalyses which reaction
fructose-6-phosphate —>fructose-1,6-bisphosphate
Purpose of Adenylate kinase
Can convert the ADP from PFK-1 to ATP
AMP is an allosteric activator of PFK-1
ATP causes allosteric inhibition of PFK-1
Other PFK-1 regulators
- Citrate allosterically inhibits PFK-1
- Fructose-2,6-bisphosphate allosterically activates PFK-1 →
=↑ rate of glycolysis & so fructose-1,6-bisphosphate production
Fructose-1,6-bisphosphate activates pyruvate kinase in the liver
High insulin levels (fed state) increase production of fructose-2,6-bisphosphate
High glucagon levels (fasting state) reduce production of fructose-2,6-bisphosphate
Functions of glycolysis
1 Provides ATP 2 Generates precursors for biosynthesis: -Intermediates converted to -ribose-5-P (nucleotides) -amino acids serine, glycine, cysteine -Pyruvate transaminated to alanine -Pyruvate substrate for fatty acid synthesis -Glycerol-3-P is backbone of triglycerides
Krebs Cycle - 4
Also known as the citric acid cycle and the tricarboxylic acid (TCA) cycle
Pyruvate transported into mitochondrion
Converted into acetyl co-enzyme A (aka acetyl CoA)
Acetyl CoA condenses oxaloacetate with acetate
Oxaloacetate regenerated in the Krebs’ cycle
Overall reaction:
acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O
2 CO2 + 3 NADH + FADH2 + GTP + 3 H+ + CoA
Pyruvate to acetyl-CoA
Pyruvate dehydrogenase multienzyme complex within mitochondrial matrix
Irreversible reaction:
pyruvate
dehydrogenase
pyruvate + CoA + NAD+ —> acetyl-CoA + CO2 + NADH + H+
Inhibited by high concentrations pyruvate, acetyl-CoA, and NADH
Activated by phosphorylation
Inactivated by phosphate removal
Citrate synthase regulation
Mainly through oxaloacetate:citrate ratio
1 oxidative phosphorylation NADH:NAD+
2 increased NADH:NAD+ increased conversion malate to oxaloacetate
- Malate dehydrogenase reaction equilibrium favour
malate
- decreased NADH:NAD+ oxaloacetate to convert
into citrate
3 increased citrate inhibition citrate synthase
Isocitrate dehydrogenase activation = decreased citrate
- Citrate synthase reaction rate increased
Isocitrate DH regulation
1 Rate limiting enzyme of Krebs’ Cycle
2 Isocitrate DH (or ICDH) made up of subunits
3 Isocitrate binds IDCH subunit = conformational change in other IDCH subunits to active form = reaction rate
- Cooperativity
ADP is an ICDH allosteric activator
-ADP binds ICDH = all ICDH subunits in active form
-Increases ICDH apparent Km = reaction rate
NADH is an ICDH allosteric inhibitor
alpha-ketoglutarate DH regulation
Mainly through inhibition by its products NADH and succinyl-CoA
May be inhibited by GTP
Activated by Ca2+ -> may be useful in generating ATP during intense muscle exercise