What are the two shunts found in erythrocyte glycolysis?
Rapaport-Luberin shunt - generates 2,3 BPG which regulates oxygen binding to hemoglobin
generates NAD+ and NADH to reduce Fe3+ in hemoglobin to Fe2+
Describe the pentose phosphate pathway.
bypasses the first stage of glycolysis to generate NADPH for other reactions and pentose sugars such as ribose 5-phosphate for nucleotide synthesis
What is the key regulatory enzyme of the pentose phosphate pathway?
glucose 6-phosphate, NADPH is a strong product inhibitor
How do cells deal with superoxide radicals?
catalase, glutathioine oxidation, or iron oxidation
anabolic rections of the TCA cycle
amino acids and neurotransmitters from OAA and a-KG
heme synthesis from succinyl CoA
glucose from malate
fatty acids and cholesterol from citrate
a reaction that returns carbons to the TCA so that the cell can continue oxidizing acetyl CoA
What are the major anaplerotic reactions in a cell?
alanine and serine conversion to pyruvate, branched chian amino acids, propionyl CoA and glutamate from the blood
Why can't acetyl CoA be used in an anaplerotic reaction?
if acetyl CoA is used, there will be no net conversion to oxaloacetate, only a buildup of citrate
uses a covalently attached biotin cofactor to convert pyruvate into oxaloacetate
positively regulated by high acetyl-CoA levels
Describe the process of fatty acid synthesis.
build up of citrate, export into the cytoplasm, conversion to OAA to generate acetyl CoA which is used for fatty acid synthesis, remaining malate goes back into pyruvate
Where does the NADPH equivalents necessary for fatty acid synthesis come from?
mainly from the pentose-phosphate pathway and the malate to pyruvate conversion
fatty acid synthase
single enzyme with three different domains and seven catalytic functions
antiparallel arrangement of the domains so that the exchange is happening between the different subunits and not within the subunit itself
synthesizes up to C16 fatty acids due to a stearic problem
elongation of fatty acids
condensation, reduction, dehydration, and reduction
acetyl-coA initiates synthesis and then malonyl CoA extends
desaturation of fatty acids
involves cytochrome b5, molecular oxygen, and NADH
How is fatty acid synthesis regulated to ensure that fatty acid metabolism isn't occuring at the same time?
inhibition of CPTI by malonyl CoA, preventing fatty acid import into the mitochondria
Describe the process of synthesizing ketone bodies.
synthesized when fatty acid levels are elevated during fasting, starvation or as the result of a high fat low carbohydrate diet
regulation of ketone body synthesis
increase CPTI activity increases fatty acid import, increase in beta-oxidation increases acetyl CoA leads to synthesis of ketone bodies
synthesis of triacylglycerols
glycerol-3-P is the first major contributor
happens in the ER
start with acetyl CoA and acetoacetyl CoA, reduced by HMG-CoA reductase, generates squalene, lanestrol, and eventually cholesterol
improtant for membranes
What are the three irreversible reactions of glycolysis that need to be circumvented by gluconeogenesis?
carboxylation of pyruvate by pyruvate carboxylase
PFK-1 conversion of F-6-P to F-1,6-P
Glucose to G-6-P by hexokinase
conversion of pyruvate to PEP
can be done in the mitochondria by phosphoenolpyruvate carboxykinase (PEPCK) and then shuttled out
can also be done in the cytoplasm after OAA has been converted to malate or aspartic acid and shuttled out
Describe the gluconeogenesis pathway.
fructose 1,6-bisphosphatase is inhibited by AMP and activated by ATP, in liver and kidney, fructose 2,6-bisphosphate is an allosteric inhibitor
Describe the process of glycogen synthesis.
related to galactose pathway because UDP glucose generates UDP galactose
glucogenic amino acids
glutamate, arginine, histidine, glutamine, proline, aspartate, asparagine, tyrosine, phenylalanine, methionine, threonine, isoleucine, valine, threonine, tryptophan, glycine, alanine, serine, cysteine
ketogenic amino acids
threonine, lysine, leucine, isoleucine, tryptophane, phenylalanine, tyrosine, leucine
What amino acids form a-KG?
glutamate, arginine, histidine, glutamine, proline
What amino acids form oxaloacetate?
aspartate and asparagine
What amino acids form fumarate?
aspartate, tyrosine, phenylalanine
What amino acids form succinyl CoA?
methionine, threonine, isoleucine, valine
What amino acids form pyruvate?
threonine, tryptophan, glycine, alanine, serine, cysteine
What amino acids form acetyl CoA?
threonine, lysine, leucine, isoleucine, tryptophan
What amino acids form acetoacetate?
phenylalanine, tyrosine, leucine