Metabolism Flashcards
Metabolism that occurs in Mitochondria
beta-oxidation for FA oxidation, acetyl-CoA production, TCA cycle, oxudative phosphorylation
Metabolism in the Cytoplasm
Glycolysis, FA synthesis, HMP shunt, protein syn in rER, steroid syn in sER, cholesterol synthesis
Metabolism in both mitochondria and cytoplasm
Heme synthesis, Urea cycle, Gluconeogeneis
Kinase
Uses ATP to add high-energy phosphate group unto substrate
Phosphorylase
Adds inorganic phosphate onto substrate without using ATP
Phosphatase
removes phosphate group from substrate
Dehydrogenase
catalyzes oxidation-reduction reactions
Hydroxylase
adds hydroxyl group onto substrate
Carboxylase
Transfers CO2 groups with the help pf biotin
Mutase
Relocates a functional group within a molecule
ex is vitB12-dependent methylmalonyl-CoA mutase
Rate-determining enzyme for Glycolysis
Phosphofructokinase
inhibited by ATP and citrate
Rate-determining enzyme for Gluconeogenesis
Fructose-1,6-Bisphosphatase
inhibited by AMP and F2,6BP
Rate-determining enzyme for TCA cycle
isocitrate dehydrogenase
inhibited by ATP and NADH
Rate-determining enzyme for Glycogenesis
Glycogen Synthase
inhibited by epinephrine and glucagon
Rate-determining enzyme for Glycogenolysis
Glycogen Phosphorylase
inhibited by G6P, insulin and ATP
Rate-determining enzyme for HMP shunt
G6PD
inhibited by NADPH
Rate-determining enzyme for de novo pyrimidine synthesis
Carbamoyl phosphate synthetase II or CPSII
Rate-determining enzyme for de novo purine synthesis
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
inhibited by AMP, IMP, GMP
Rate-determining enzyme for urea cycle
Carbamoyl phosphate synthetase I (CPSI)
Activated by N-acetylglutamate
Rate-determining enzyme for FA synthesis
Carnitine acyltransferase I
inhibited by malonyl-CoA
Rate-determining enzyme for Ketogenesis
HMG-CoA synthase
Rate-determining enzyme for Cholesterol Synthesis
HMG-CoA reductase
inhibited by glucagon and cholesterol
activated by insulin and thyroxine
Galactokinase
galactose → galactose-1-phosphate
Galactose-1-phosphate uridyltransferase
galactose-1-phosphate → glucose-1-phosphate
Hexokinase/Glucokinase
Glucose ↔ Glucose-6-P
G6PD
Glucose-6-P→ 6-phosphogluonolactone
HMP shunt
lack of this causes von Gierke’s
Phosphofructokinase
rate limiting step in glycolysis
makes fructose-6-P → F1,6P
to reverse this you would need F1,6Bisphosphatase which is rate limiting for gluconeogenesis
Adolase B
found in liver
A is in muscle
Pyruvate Kinase
PEP to pyruvate
Pyruvate dehydrogenase
requires thiamine cofactor TPP
Pyruvate → acetyl-CoA
Pyruvate Carboxylase
Requires Biotin
Pyruvate → Oxaloacetate
Isocitrate Dehydrogenase
Rate limiting step in TCA,
Isocitrate → alpha-ketoglutarate
Ornithine Transcarbamylase
Requires TTP
alpha-ketoglutarate → succinyl-CoA
ATP production in the heart and liver
net 32 ATP, malate-aspartate shittle
ATP production in the muscle
net 30 ATP, uses glycerol-3-phosphate shuttle
ATP production in Anaerobic Glycolysis
net 2 ATP per glucose molecule
Phosphoryl groups
carried by ATP
Electrons
carried by NADH, NADPH, FADH2
Acyl groups
carried by CoA, lipoamide
CO2 carried by
Biotin
1 carbon units
carried by tetrahydrofolates
CH3 groups
carried by SAM
Aldehydes
Carried by TPP
Product of HMP Shunt
NADPH
Use of NADPH
anabolic processes like steroid and FA synthesis
respiratory burst
cytochrome P450 system
glutathione reductase
Low Km
High affinity
Low Vmax
Low capacity
Glucokinase
induced by insulin, high Km, found in liver and beta-cells of pancreas
Mutated in MODY
Glucokinase
hexokinase
Low Km, Low Vmax, in most tissues except liver and beta cells of pancreas
inhibited by glucose-6-P
Enzymes that require ATP in glycolysis
hexokinase/glucokinase
phosphofructokinase-1
Enzymes that produce ATP in glycolysis
Phosphoglycerate kinase
Pyruvate Kinase
Purely ketogenic amino acids
Lysine and Leucine
Pyruvate dehydroxylase complex deficiency
causes a build up or pyruvate that gets shunted to lactate via LDH and alanine via ALT
neuro issues, lactic acidosis, increased serum alanine in infancy
Tx for Pyruvate dehydroxylase complex deficiency
increase ketogenic nutrients, high fat content of increase lysine and leucine
Complex I of ETC
uses NADH electrons and pumps out hydrogen into intermembrane space of mitochondria
inhibited by Rotenone
Complex II of ETC
uses FADH2 electons
succinate dehydroxynase
Complex III of ETC
take electrons from CoQ and pumps hydrogen into intermembrane space
inhibited by Antimycin A
Complex IV
takes electrons from cytochrome C, makes water
pumps hydrogen into the intermembrane space
inhibited by cyanide and CO
ATP synthase
makes ATP and pushes H into mitochondria matrix
inhibited by Oligomycin
Uncoupling Agents
2,4-Dinitophenol, aspirin, thermogenin in brown fat
increases permeability of mitochondrial membrane
decreases hydrogen gradient and increases oxygen consumption
products heat
Glucose-6-phosphatase
occurs in ER to make glucose
an irreversible enzyme
Odd-chain FA
yield 1 propionyl-CoA during metabolism, which can enter the TCA cycle as succinyl CoA
can also undergo gluconeogenesis
Even-chain FA
can’t produce glucose, only yield acetyl-CoA
Purpose of HMP Shunt
provides a source of NADPH which is required to reduce glutathione inside RBCs to prevent destruction and for FA and cholesterol biosynthesis
Sites of HMP Shunt
Lactating mammary glands, adrenal cortex for steroid syn, RBCs
Oxidative HMP shunt Enzyme
Glucose-6-dehydrogenase, rate limiting step the make G6P into 2NADPH, CO2, and ribulose-5-P
Nonoxidative HMP shunt enzyme
phosphopentose isomerase, transketolase (req B1)
makes ribulose5P into ribose5Pi, G3P and F6P
NADPH oxidase deficiency
chronic granulomatous disease
Steps of Oxidative Respiratory Burst
NADPH oxidase, Superoxide dismutase, myeloperoxidase, glutathione peroxidase (req selenium), glutathione reductase (req selenium), G6PD
Pyocyanin
P. aeruginosa tonxin that generates ROS to kill competing microbes