Flashcards in Week 3 Nutrition Disorders Associated with Bioenergetics Lecture Deck (51):
All three macronutrients will converge to form what molecule that feeds into a major energy production pathway?
what are the products of glycolysis
2 ATP (4 net - 2ATP in prep phase), 2 NADH, 2 pyruvate
in order for the oxidative phosphorylation of glycolysis dervied NADH to occur where what must occur and how?
NADH must enter the mitochondria. this can occur via the malate-aspartate shuttle or the glycerol 3-phosphate shuttle
how much ATP can be made from one molecule of glucose?
in glycolysis ATP is produced by ....which does not require....
substrate level phosphorlyation which does not require Oxygen
All amino acids can be broken down into what...
1 of 7 metabolites that can feed into the TCA cycle
what are ketogenic AA?
amino acids that are used for the synthesis of ketone bodies, that cannot feed into gluconeogenesis (these structure produce acetly-CoA which cannot be converted back to pyruvate)
what are glucogenic AA?
AA that have carbon skeletons that can be used for gluconeogenesis during starvation
Arsenate does what?
decouples ATP synthesis by interfering with Glycerladehyde-3-phosphate dehydrogenase. G3PD puts arsenate on G-3-P instead of phosphate. This becomes a problem becasue 1,3-BPG is not created and therefore ATP in not produced when it is converted to 3-PG.
G3P-->1,3-BPG-->3-PG and ATP
what does arsenite do?
inhibits pyruvate dehydrogenase. Pyruvate is not converted to acetyl-CoA
What is lactic acidosis?
the symptom that results from an accumulation of lactate (lactic acid) due to the inability of Pyruvate to be converted to acetyl-CoA and enter the TCA cycle.
what are some causes of lactic acidosis?
Anything that causes pyruvate to accumulate: exercise (anaerobic glycolysis in muscle), pyruvate dehydrogenase deficiency (arsenite poisoning), eleaveted NADH/NAD+ ratio (NAD+ is needed for Pyruvate dehydrogenase to work)
what does pyruvate kinase do?
converts PEP to pyruvate and produces ATP
Pyruvate kinase deficiency presents as what? what cell type is it seen in?
Chronic Hemolytic Deficiency. the isozyme of PK that is affected is in RBCs.
pyruvate kinase deficiency causes what?
lack of ATP in RBCs interferes with Na/K ATPase and causes ion imbalance. the RBC acquire abnormal morphology and splenic hemolysis occurs.
Pyruvate Kinase Deificiency also causes the accumulation of what? why is this bad?
2,3-BPG (upstream of the 'dam"). 2,3-BPG allosterically inhibits hexokinase which further decreases glycolysis AND has allosteric effects on Hb favoring the T-state and causing anemia.
how prevalent is pyruvate kinase deficiency
1:20,000 whites. second most common cause of Chronic hemolytic anemia next to G6PD deficiency
where does the TCA cycle occur?
where is pyruvate dehydrogenase located? what is its fucntion
mitochondria, converts Pyruvate to Acetyl-CoA
what is the function of pyruvate carboxylase?
converts pyrvate to oxaloacetate with biotin as a cofactor
what does a PC deficiency result in? 3
pyruvate buildup (lactic acidosis), hypoglycemia, decrease in myelin sheath and neurotransmitters
oxaloacetate is an important precursor for what? 3
gluconeogenesis, production of myelin sheath and neurotransmitters
what are some symptoms of PC deficiency?
lactic acidosis, failure to thrive, neurological dysfunction
how common is PC deficiency?
rare, 1:250,000 live births
how can PC deficiency be treated?
depends on mutation but can try glucose administration, biotin, citrate (get TCA cycle going), triheptanoin (can be used to make ketone bodies converted back to acetyl CoA)
pyruvate dehydrogenase (PDH) deficiency results in what? 3
limited acetyl-CoA, ATP decrease, and pyruvate accumulation (Lactic acidosis)
what is clinical heterogeneity?
same muation with different presentation
PDH def is what type of inheritance?
X-linked, although it is clinically heterogenous and seen equally in males and females (random X-inactivation)
why is dichloroacetate a treatment for PDH deficiency?
inhibits the kinase that deactivates the enzyme used in PDH complex (thus allows for acetly-coa production)
what does cyanide poisoning do?
blocks cytochrome oxidase (complex IV) of ETC by binding iron
what are the effects of cyanide poisoning?
massive lactic acidosis due to a switch to anaerobic glycolysis
there are trace amounts of cyanide in nuts, how do we not die?
the enzyme rhodanase in liver detoxifies these
What is oxphos disease caused by?
caused by mutation in DNA that codes for proteins associated with oxidative phosphorylation
what is Myoclonic Epilepsy and Ragged-Red Fiber Disease?
mitochondrial disorder caused by point mutation in the mtDNA gene that encodes for tRNAlys
how does MERRF manifest?
late onset, muscle twitching, clumps of diseased mitochondria appear in muscle fiber (stain red)
what is Leber's hereditary optic neuropathy
mitochondrial disorder that is caused by mutation in Complex I of ETC
how does leber's hereditary optic neuropathy present itself?
acute blindness cuased by degeneration of optic nerve
what is idebenone? what does it treat
a compound that boosts electron transport chain by bypassing Complex I (treates leber's hereditary optic neuropathy)
which organs rely mostly on FA oxidation for energy?
heart, muscle, liver
what is MCAD deficiency?
an impaired ability to break down medium chain FA (C6-C12)
how does MCAD present itself?
hypoketonic hypoglycemia triggered by prolonged fasting or exercise
how do you treat MCAD?
high carb diet, acvoidance of fasting
what is CPT II used for?
transport of FA into mitochondria
CPT II def presents as?
rhabdomylosis: muscle breakdown and release of myoglobin
what casues jamaican vomiting syndrome?
eating unripe Akee fruit produces MCPA which inhibits FA oxidation
what is role of porpionyl-CoA carboxylase
plays a role in carboxylatin 3C FA that cannot be broken down into acetyl-CoA otherwise. has a biotin cofactor
what does propionyl-CoA carboxylase deficiency result in?
persoxisomes break down which FAs
VLCFA and branched FA
what are the disorders associated with peroxisomal FA oxidation?
x-linked adrenoleukodystrophy (cant transport VLCFA), zellweger syndrome (no peroxisome produced), adult refsum disease (loss of alpha oxidation, branched FA accumulate)
why is buildup of VLCFA and branched FA bad?
disrupts myelin sheaths, neurologic damage, loss of motor fucntion