Flashcards in Biochem II Deck (48):
You get a build up of ________ with pyruvate dehydrogenase deficiency. How can you get this deficiency?
X-linked congenital defect
B vitamin deficiency--especially thiamine (B1) in alcoholics
What is the treatment for pyruvate dehydrogenase deficiency?
high fat diet
ketogenic AA (lysine, leucine)
What does one acetyl CoA yield? In the TCA cycle
What is 1 NADH worth? 1 FADH2?
1 NADH=2.5 ATP
1 FADH2=1.5 ATP
Which complex of the TCA cycle is NADH fed into? FADH2?
NADH-->Complex I, NADH reductase
FADH2-->Complex II, Succinate Dehydrogenase
What are some things that can negatively affect Complex I?
Rotenone (Fish poison)
MPP (from MPTP synthetic opioid)-->can cause parkinsonism
WHat are some things that can negatively affect Complex III?
Antimycin A (fish poison)
What are some things that can negatively affect Complex IV?
N3 (sodium azide)
H2S (hydrogen sulfide)
What is something that can inhibit ATPase of ETC?
Oligomycin A (macrolide, not used clinically)
What are some agents that can uncouple oxidative phosphorylation in the ETC and generate heat? MOA?
**increase permeability of the inner mitochondrial membrane, H+ rushes down the gradient, get heat
thermogenin (found in brown fat of hibernating bears, need heat!)
2, 4 dinitrophenol (weight loss pill, deadly)
Describe the Cori cycle.
In muscles or RBCs when there is anaerobic metabolism, only glycolysis, get all of these pyruvates that are converted into lactic acid.
They are shuttled over to the liver where they are converted back to pyruvate by lactate dehydrogenase
then Pyruvate is converted back to glucose to be shipped back to muscle or RBCs
**get 2 ATP from anaerobic glycolysis, takes 6 ATP to make the glucose from lactic acid.
What is the basic purpose of the alanine cycle?
basically, muscle uses protein for energy and gives the excess nitrogen to the liver to be excreted as urea by the kidney. Given in the form of glutamine and alanine.
The liver in return gives glucose to the muscle.
Describe the alanine cycle.
AA-->ketoacids, alpha ketoglutarate-->glutamate
glutamate -->glutamine. Transfer to liver. Goes into urea cycle.
Glucose -->Pyruvate-->Alanine. Transfered to liver to make glucose again, which is shipped back.
What do transaminases (aka aminotransferases) do in the alanine cycle?
Takes place in the liver.
cause the formation of AA to alpha ketoacids by transferring nitrogen onto alpha ketoglutarate to make glutamate
and alpha ketoacids are used for energy metabolism. Get glucose from them that is transferred back to muscle.
What are the 2 most important transaminases?
ALT (alanine aminotransferase)
AST (aspartate transaminase)
Describe the reaction accomplished by AST.
aspartate + alpha ketoglutarate--> oxaloacetate + glutamate
Describe the reaction accomplished by ALT.
alanine + alpha ketoglutarate-->pyruvate + glutamate
What is the cofactor needed for AST/ALT and other transaminases to work?
What are the 2 nitrogen transporters in the blood?
What are the enzymes required for pyruvate dehydrogenase complex to work?
TLC For Nobody
CoA/Vit B5/pantothenic acid
What does arsenic do to the pyruvate dehydrogenase complex?
inhibits lipoic acid
rice water stools
Which other enzyme requires the TLC For Nobody cofactors as well?
alpha ketoglutarate dehydrogenase
What are the things that pyruvate can be converted into?
Acetyl CoA (via pyruvate dehydrogenase)--TCA
Lactic acid (via lactate dehydrogenase)--Cori Cycle
Oxaloacetate (via pyruvate carboxylase)--gluconeogenesis
Alanine (via ALT)--Alanine Cycle/Cahill cycle
What are the important things to remember about the TCA cycle?
1st enzyme: citrate synthase:
Rate limiting enzyme: isocitrate dehydrogenase:
alpha KG dehydrogenase
alpha KG-->succinyl CoA
energy output: 1 GTP, 3 NADH, 1 FADH2, 2 CO2
where does the pentose phosphate pathway take place?
mammary glands (during lactation)
**think about FA and cholesterol synthesis
**think about dealing with ROS damage
What do you get from the HMP shunt/Pentose Phosphate Pathway?
What is ribose-5-P from PPP used for?
ribulose-5-P-->PRPP used in ribonucleotide synthesis, think pyrimidines and purines
What are the purposes for NADPH produced by the PPP?
1. glutathione reduction in RBCs
2. fatty acid and cholesterol biosynthesis
3. Generation of ROS in phagolysosomes
4. Function of CytP450 enzymes
Where does pentose phosphate pathway/HMP shunt take place? What are the 2 phases?
all in the cytosol
1. Oxidative (irreversible)
2. nonoxidative (reversible)
What is the most important enzyme in the PPP?
glucose-6-P-->2 NADPH + Ribulose-5-P
Describe NADPH function in the phagolysosome.
O2-->O2- (superoxide) via NADPH oxidase
O2- -->H2O2 via superoxide dismutase
H2O2-->HOCl via myeloperoxidase
Once again, which organisms are patients with chronic granulomatous disease susceptible to?
catalase + organisms that can break down H2O2
b/c when you have NADPH oxidase deficiency, you depend on hydrogen peroxide to kill bugs.
G6PD deficiency is inherited how? More common in which ethnicity? One good thing about it?
possible increased malarial resistance
What are the histo things you see with G6PD deficiency?
Heinz bodies (inclusion from denatured hemoglobin)
Bite cells (from splenic macrophages)
Why is glutathione important in RBCs? How do you keep it reduced and functional?
H2O2-->H2O via glutathione peroxidase (oxidizes glutathione)
Replenish glutathione via glutathione reductase, which requires NADPH
get that NADPH via G6PD dehydrogenase of PPP
Which drugs are patients with G6PD deficiency more susceptible to injury from? B/c they can't replenish their glutathione in RBCs? With these drugs get hemolytic anemia
Spleen purges nasty inclusions from damaged cells
Nitrofurantoin (antibiotic for UTI, safe in pregnancy)
dapsone (antibiotic used in leprosy)
What is different about the hemolytic anemia produced by glycolysis enzyme deficiency and that produced by G6PD deficiency?
Glycolysis enzyme deficiency, ex: pyruvate dehydrogenase
buildup of lactic acid or something, can't get energy, eventually swell up and lyse
G6PD deficiency get hemolytic anemia via ROS damage and splenic macrophages taking a bite out of you
Describe the basics of fructose metabolism.
Fructose-->(via fructokinase)-->F-1-P-->(via aldolase B)-->Dihydroxyacetone + glyceraldehyde
Which enzyme deficiency produces essential fructosuria? Symptoms?
relatively asymptomatic b/c don't get accumulation of fructose in cells b/c it hasn't been phosphorylated yet
fructose appears in blood and urine
How are the fructose and galactose errors of metabolism inherited?
What is the enzyme deficiency that leads to fructose intolerance? Symptoms?
aldolase B deficiency
get buildup of F-1-P in cells and decrease available phosphate, inhibiting glycogenolysis and gluconeogenesis
get hypoglycemia, hepatomegaly, jaundice, cirrhosis, vomiting
After consumption of which foods would you see bad symptoms w/ fructose intolerance? Treatment?
after consumption of fruit, juice, honey
Treatment: decrease intake of fructose and sucrose (fructose + glucose)
Which enzyme deficiency leads to galactokinase deficiency? symptoms?
galactitol accumulates, esp in lens and can cause infantile cataracts
other than that asymptomatic
Which enzyme deficiency causes classic galactosemia? Symptoms?
get accumulation of galactitol-->infantile cataracts
failure to thrive
increases susceptibility to E coli as neonate
What is the treatment for classic galactosemia?
exclude galactose and lactose from diet
lactose=galactose + glucose
Describe galactose metabolism.
Galactose-->(via galactokinase)-->galactose-1-phosphate-->(via uridyltransferase)-->Glucose-1-Phosphate
excess galactose-->galactitol via aldose reductase
Which ethnicities is lactose intolerance common in? Aside from hereditary deficiency, what else can cause this intolerance?
Common in african americans, native americans, Asians
loss of brush border due to gastroenteritis