FA Biochem III Flashcards
What fxn does glucokinase serve in the liver
phosphorylation excess glucose to sequester it, liver becomes blood glucose buffer
What are the reactants for glycolysis
glucose, 2Pi, 2ADP, 2NAD+
What are the products for glycolysis
2 pyruvate, 2ATP, 2NADH, 2H+, 2H2O
What two rxns in in glycolysis require ATP
glucose to G-6P, hexokinase and fructose-6P to fructose 1,6 BP phosphofructokinase-1
What substances inhibit phosphofructokinase-1
ATP, citrate
What substances induce phosphofructokinase
AMP, fructose 2,6 BP
What rxn creates ATP
phosphenolpyruvate to pyruvate catalyzed by pyruvate kinase
What inhibits pyruvate kinase
ATP and alanine
What induces pyruvate kinase
F16BP
What enzyme catalyzes the rxn from pyrvuate to Acetyl-CoA and what inhibits it
pyruvate dehydrogenase, ATP, NADH, acetyl-CoA
In which state is FBPase-2 active
fasting
In which state is PFK-2 active
fed
What regulates whether FBPase-2 or PFK-2 is active
protein kinase A
What is the pathway in the fasting state leading to inc FBPase-2 and dec PFK-2
inc glucagon, inc cAMP, inc PKA
What is the pathway in the fed state leading to dec FBPase-2 and inc PFK-2
inc insulin, dec cAMP, dec PKA
The pyruvate dehydorgenase complex serves in what reaction: reactants
pyruvate, NAD+, CoA
The pyruvate dehydrogenase complex serves in what reaction: products
Acetly-CoA, CO2, NADH
What co-factors are required for the pyruvated dehydrogenase complex
pyrophosphate (B1, thiamine, TPP) FAD (B2, riboflavin), NAD (B3, niacin), CoA (B5 pantothenate), lipoic acid
What activates the pyruvate dehydrogenase complex
exercise: inc NAD/NADH, inc ADP, inc Ca
What other complex is similar to the pyruvate dehydrogenase complex in that it has the same co-factors and generates succinyl-CoA
alpha-ketoglutarate dehydrogenase complex
What does arsenic do and what are th results of poisoning
inhibits lipoic acid, vomiting, rice water stools, garlic breath
What does a pyruvate dehydrogenase deficiency lead to and what are the findings
backup of substrate (pyruvate and alanine) resulting in lactic acidosis, congenital or acquired from thiamine def in EtOH, neuro defects
What is the TX for pyruvate dehydrogenase deficiency
inc intake of ketogenic nutrients, high in fact content or inc lysine or leucine
What are the only purely ketogenic amino acids
Lysine and leucine
Of the four possible fates for pyruvate, which one carries amino groups to liver from muscle
alanine
Of the four possible fates for pyruvate, which one can replenish TCA cycle or be used in gluconeogenesis
Oxalacetate
Of the four possible fates for pyruvate, which one is a transition from glycolysis to TCA cycle
Acetyl-CoA
Of the four possible fates for pyruvate, which ends anaerobic glycolysis as in RBCs, leukocytes, kidney medulla, lens, testes and cornea
Lactate
What does the TCA cycle produce per 1 acetyl CoA
3 NADH, 1 FADH2, 2 CO2, 1 GTP = 12 ATP (x2 per glucose)
What does Citrate Is Krebs starting substrate for making oxaloacetate
citrate, isocitrate, alpha ketoglutarate, succinyl-CoA, succinate, fumarate, malate, oxaleoacetate
How doe NADH electrons from glycolysis and the TCA cycle enter the mitochondiria
malate-aspartate shuttle or the glycerol 3 phosphate shuttle
What does the passage of electrons result in that when coupled to OXPHOS drives the production of ATP
proton gradient
Where are FADH2 electrons transferred to
comlex II
What substances directly inhibit electron transport chain
rotenone, CN-, antimycin A, CO
Wgat substances directly inhibit mitochondrial ATPase, causing an inc in proton gradient, no ATP because pump is stopped
oligomycin
What are uncoupling agents
inc permeability of membrane causing a dec in proton gradient and inc in O2 consumption - ATP synthesis stops, but electron transport continues to produce heat
What substances are uncouling agents
2,4 DNP, aspirin
What are the irreversible enzymes of gluconeogenesis
pyruvate carboxylase, PEP carboxykinase, fructose 1,6 biphosphatase, glucose 6 phosphatase
Where is pyruvate carboxylase found, what does it do, what does it require amd what activates it
in mitochondria, pyruvate to oxaloacetate, requires biotin, ATP, activated by acetyl coA
Where is PEP carboxykinase found, what does it do, and what does it require
in cytosol, oxaloacetate to phosphenolpyruvate, requires GTP
Where is fructose 1,6 bisphosphatase found and what does it do
cytosol, F 1,6 BP to fructose 6 Phosphate
Where is glucose 6 phosphatase found and what does it do
in ER, glucose 6-P to glucose
Where does gluconeogenesis primarily happen and what are other sites where the enzymes are located
liver, also in kidney and gut epithelium
What do def in in enzymes of gluconeogenesis cause
hypoglycemia
Why can’t muscle produce in gluconeogenesis
lacks glucose 6 phophatase
How do odd chain fatty acids participate in gluconeogenesis
via 1 proprionyl-CoA which can enter the TCA as succinyl-CoA and undergo gluconeogenesis
Why can’t even chain fatty acids produce new glucose
they yield only acetyl-CoA equivalents
What is the purpose of the HMP shunt
provide a source of NADPH from an abundantly available glucose 6P, create ribose for nucleotide synthesis and glycolytic intermediates
What are the 2 distinct phases of the HMP shunt and how many ATP are used and produced
oxidative and nonoxidative, no ATP produced or used
Which phase of the HMP shunt is reversible and which is irreversible
oxidative is irreversible
What happens on the oxidative arm of the HMP shunt and what is the key enzyme
glucose 6P to CO2, 2NADPH, ribulose 5P, G6PD, rate limiting step
What happens on the nonoxidative arm of the HMP shunt and what is the key enzyme and cofactor
ribulose 5P to ribose 5P, G3P and F6P, transketolase and B1
What does NADPH oxidase deficiency result in and why
chronic granulomatous disease, no respiatory burst, no formatino of ROS
What enzyme turns ROS to H2O2
superoxide dismutase
What enzyme adds Cl- to the H202 to makes bleach
myeloperoxidase
In what cells do the respiratory burst occur
PMNs
What substance inside the cell serves to oxidize glutatione
peroxide
What substance inside the cell reduces glutatione
NADPH
What substance inside the cells replenishes NADPH
G6PD
Patients with chronic granulomatous disease are at increased risk of infection from which kind of organisms
catalase positive (catalase neg produce H2O2 the cell can use) like S. aureus or aspergillus
What is NADPH’s role inside RBCs
keep glutathione reduced so it can detoxify free radicals and peroxides
What does a decrease in decrease in NADPH lead to and why
poor defense from oxidizing agents, fava beans, sulfonamides, primaquine, antituberclosis drugs leadig to hemolytic anemia.
What other inflammatory process can induce a hemolytic anemia in NADPH defieicnt patients
infection, free radicals generated by inflammatory response
Why is G6PD def more common among patients of african decent
protective against malaria
What are Heinz bodies
oxidized hemoglobin precipiated within RBCs
What are bite cells and when do you see them
result from phagocytic removal of heinz bodies my macs - G6PD def
benign asymptomatic condition with elevated levels of fructose in urine and blood, dz and enzyme
essential fructosuria - fructokinase AR
What is the defect in fructose intolerance and what does it cause
aldolase B, AR, fructose 1P accumulates causing a dec in availabel phosphate which inhibts glycogenolysis and gluconeogenesis leading to hypoglycemia, cirrhosis, jaundice and vomiting
What enzyme does fructose metabolism bypass to reach glycolysis
PFK - rate limiting enzyme
What are possilbe presentation for galactokinase def
failure to track objects or develop a social smile
What substance accumulates in galactokinase def and what is the clinical picture
galactitol, galactose appears in blood and urine, can cause infantile cataracta - AR
What enzyme results in classic galactosemia and what is the clinical
absence of galactose 1 phosphate uridyltransferase, accumulation of toxic substances leads to failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
In addition to fructose and galactose, what sugards should be excluded from the diets of patients with disorders of fructose or galactose metabolism
sucrose = glucose + fructose, lactose = glucose + galactose
What is sorbitol, how and why is it made
alcohol version of glucose, can trap glucose in cell, aldose reductase
What sugar is sorbitol converted to and via what enzyme, and what can happen in cells lacking this enzyme
fructose via sorbitol dehydrogenase, inc sorbitol leading to osmotic damage as in cataracts, retinopathy, peripheral neuropathy as in diabetes
What tissues have both enzymes of sorbitol metabolism
liver, ovaries, seminal vesicles
What tissues have only aldose reductase
schwann cells, lens, retina, kidneys
What does lactase deficiency cause
loss of brush border enzyme causing bloating, cramps, osmotic diarrhea
Who typically has lactase def
African Americans and Asians
What form of amino acids are found in proteins
L form
What are the glucogenic essential amino acids
met, val, arg his
What are the glucogenic/ketogenic amino acids
Ile, phe, thr, trp
What are the purely ketogenic amino acids
leu, lys
Which are the acidic amino acids
Asp and Glu
Which are the basic amino acids
arg, lys, his, arg is most basic, has has no charge at body pH
What two amino acids are required druing periods of growth and why
arg and his inc in histones which bind negatively charged DNA
What does amino acid catabolsim results in the formation of what
common metabolites like pyruvate and acetyl CoA and excess NH4+ converted to urea and exreted
What step begins the urea cycle and what is the enzyme needed, where does it happen
CO2 + NH4 needs carbamoyl phosphate synthase I, in the mitochondria
When does aspartate enter the urea cycle
after citruline
What is the composition of urea and where do each part derive from
NH2-(C=O) -NH2 one NH2 from ammonia the C=O from CO2, and the other NH2 from aspartate
How is ammonium transported from muscle to the liver for urea cycle
passed to glutamate, then to alanine enters blood, enters liver, coverted to pyruvate and transfers ammonium back to glutamate which gives it to the urea cycle
What happens in hyperammonemia
depletes alpha-ketoglutarate leading to inhibition of TCA cycle - tremor slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
What is the TX for hyper ammonemia
limit protein diet, benzoate or phenylbutarate (both bind amino acids leading to excretion) can decrease ammonia levels
What is the most common urea cycle disorder and what is the mode of inheritance?
ornithin transcarbamoylase def - x linked recesssive, other urea cycle enzymes defs are autosommal recessive
How does OTC def present
evident in first few days of life, can present last onest, excess carbamoyl phosphate converted to orotic acid, orotic acid in blood and urine, dec BUN and symptoms of hyerpammonemia
What is the amino acid precursor for catecholamines
phenylalanine
What is the amino acid precuros for niacin and serotonin/melatonin
tryptophan
What is the amino acid precursor for histamine
histidine
What is the amino acid precursor for porphyrin and heme
glycine
What is the amino acid precuror for creatine, urea and nitric oxide
arginine
What is the amino acid precursor for GABA and glutathione
glutamate
What enzyme converts phenylalanine to tyrosin
phenylalanine hydroxylase
What converts tyrosine to DOPA
tryosine hydroxylase
What converts DOPA to dopamine
dopa decarboxylase
What converts dopamine to NE
dopamine beta hydroxylase
What converts NE to epi
phenylethamolamine N methyl transferase
What is the breakdown product of dopamine
HVA
What is the breakdown product of NE
VMA
What is the breakdown product of epi
metanephrine
decreases in what substances can cause PKU
phenylalanine hydroxylase, tetrahydrobiopterin cofactor
What enzyme becomes essential in PKU
tyrosine
What does inc phenylalanine lead to
phenylketones in urine
What are the findings in PKU
mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor
What is the TX for PKU
dec phenylalanine (contained in aspartame, Nutrasweet) inc tyrosine in diet
What is maternal PKU
lack of proper dietary therapy during pregnancy leading to microcephaly, mental retardation growth retardation, congenital heart defects
What creates the musty body odor in PKU
disorder of aromatic amino acid metabolism
congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine to fumarate leading to dark connective tissue, brown pigmented sclera, urine turns black on standing - dz and worst complication
alkaptonuria, may have debiliating arthralgias
What are the two possible causes of albinism
lack of tyrosinase (no melanin) AR ordefective tyrosine transporters (less tyrosine) - can results in lack of migration of NC cells
Pts with albinism are at inc risk for what cancer
skin
Why is albinism inheritnace varialbe due to
locus heterogeneity - ocular albinism is x-linked recessive
What are the 3 AR forms of homocystinuria
cystathionine synthase def, dec affinity of cystathionine synthase for pyridoxal phosphate, homocystein methyltransferase def
What is the treatment for cystathionine synthase def
dec methionine, inc cystiene, inc B12/folate
What is the treatment for dec affinity of cystathionine synthase for pyroxidal phosphate
inc vit B6
What are the findings with homocystinuria and what amino acid is needs to be supplemented
homocystein in ruine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation and atherosclerosis leading to stroke and MI, cysteine
What is the defect in cystinuria
hereditary defect of renal tubular amino acid transporter for cystein, ornithine, lysine and arginine in PCT
What is the complication of cystinuria
cystine kidney stones, cystine staghorn calculi - cystine is made of two cysteines connected by disulfide bond
What causes maple syrup urine disease and what does it lead to
dec in alpha ketoacid dehydrogenas leading to blocked degredation of branches amino acids like Ile, Leu, and Val - severe CNS defects mental retardation and death
What causes Hartnup’s disease
AR disorder characterized by defective neutral amino acid transporte on renal and intestinal epith cells
What does hartnups disease cause
tryptophan excretion in urine and dec absorption from the gut leading to pellagra
How do glucagon/epi lead to glycogenolysis
Adenylyl cycle, inc cAMP, inc PKA, glycogen phosphorylase kinase activated, glycogen phosphoylase active, glycolysis
How does insulin inhibit glycogenolysis
receptor tyrosine kinases, protein phosphatase, takes phosphate off glycogen phosphorylase kinase inactivating it
What else can phosphoylate phosphorylase kinase
Ca/calmodulin in muscle to coordinate with muscle activity
What kind of branches do glycogen branches have
alpha 1,6 and alpha 1,4
What happens do glycogen in skeletal muscle during exercise
glycogenolysis to form glucose
What happens to glycogen in the liver
stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels
What enzyme converts glucose 1 p to UDP glucose
UDP glucose pyrophosphorylase
What enzyme degrades a small amount of glycogen in lysosomes
alpha 1,4 glucosidase
What liberates glucose from glucose 6 P
glucose 6 phosphatase
What converts limit dextran to glucose
debranching enzyme
Very Poor Carbohydrate Metabolism stands for 4 of the glycogen storage diseases, what are thy
Von Gierke’s, Pompe, Cori, McArdle
Severe fasting hypoglycemia, inc glycogen storage in liver, inc blood lactate, hepatomegaly - dz and def enzyme
von gierkes, glucose 6 phosphatase
cardiomegaly, systemic findings leading to early death - dz and enzyme
pompe’s lysosomal alpha 1,4 glucosidase (acid maltase) (pompe trashes the pump; heart, liver, muscle)
Milder form of type I with nl blood lactate levels - dz and enzyme
cori’s, debranching enzyme alpha 1,6 glucosidase, gluconeogenesis intact
inc glycogen in muscle but can’t break it down, painful muscle cramps, myglobinuria with strenuous exercise - dz and enzyme
mcardle’s, skeletal muscle glycogen posphorylase
peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease - dz, def enzyme, acc substrate, inherit
fabrys, alpha galactosidase A, ceramide trihexoside, XR
hepatosplenomegaly, aseptic necrosis of femur, bone crisis, MACS that look like crumpled tissue paper
gaucher’s, beta glucocerebrosidase, glucocerebrosie, AR
progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells
neimann-pick, sphingomyelinase, sphingomyelin, AR
progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, NO hepatosplenomegaly
Tay-Sachs, hexosaminidase A, GM2 ganglioside, AR
peripheral neuropathy, developmental delay, optic atrophy, glopoid cells
krabbes, galactocerebrosidase, galactocerebroside, AR
central and peripheral demyelination with ataxia and dementia
metachromatic leukodystrophy, arylsulfatase A, cerebroside sulfate AR
developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
hurlers syndrome, alpha L iduronidase, heparan sulfate/dermatan sulfate, AR
Mild Hurlurs + aggressive behavior no corneal clouding
Hunters, iduronate sulfatase, heparan sulfate/dermatan sulfate, XR
What shuttle is used in fatty acid degredation and what does it move and from where to where
carnitine shuttle, acyl-coa from cyto to mito
What inhibits the carnitine shuttle
malonyl coa
What happens in carnitine def
inability to transport LCFAs into mitochondria results in toxic accumulation causing weakness, hypotonia, hyperketotic hyperglycemia
What shuttle is involved in fatty acid synthesis and what does it move from where to where
citrate, acetyl coa from mito to cyto
What does beta oxidation do and where does it occur
breaks down acyl-coa to acetyl coa groups in mito
what happens in acyl coa dehyrdogenase def
inc dicarboxylic acids, dec in glucose and ketones
What does acetyl-CoA become before becoming palmitate
malonyl coa (+ biotin= palmitiate, 1 16C fatty acid)
What enzymes metabolize fatty acids and amino acids
acetoacetate and beta hydroxybutyrate
What occurs to oxaloacetate in starvation and DKA
depleted for gluconeogenesis staling the TCA cycle and shunting glucose and FFA to production of ketone bodies
What happens to oxaloacetate in alcholism
excess NADH shunts oxaloacetate to malate (backwards) stalling the TCA and shunting glucose and FFA to ketone body production
What are ketone bodies made from, where are they metabolized and how are they excreted
HMG-CoA, brain to 2 molecules of acetyl-Coa, excreted in urine
in a 100 meter sprint where does energy come from
stored ATP, creatine phosphate, anaerobic glycolysis
In a 1000 meter run, where does energy come from
same as sprint + OXPHOS
in a marathon where does energy come from
glycogen and FFA oxidation; glucose conserved for final sprinting
What are the priorities for the body in fasting and starvation
supply sufficient glucose to brain and RBCs and to preserve protein
What is the energy source in the fed state right after a meal
glycolysis and aerobic respiration
What is the source of energy in the fasting state between meals
hepatic glycogenolysis»_space; hepatic gluconeogenesis > adipose release of FFA
What are the blood glucose levels maintained by for days 1-3
hepatic glycogenolysis, adipose tissue release of FFA, muslce and liver FFA, hepatic gluconeogenesis from peripheral tissue lactate and alanine and from adipose tissue glycerol and proprionyl-coA (odd chain FFA)
What is the energy source after day 3 of starvation
adipse tissue stores, keton bodies become the main source of energy fo the brain and heart, after these are depleted, vital protein degradation accelerates, leading to organ failure and death
When are glycogen reserves depleted
after day 1
1 g of protein or cabrohydrate = ?kcal
four
I g fat = ? Kcal
nine
What is the rate limiting enzyme in cholesterol synthesis
HMG-CoA (HMG-CoA to mevalonate
What enzyme esterifies 2/3 of plasma cholesterol
LCAT (lecithin cholesterol acyltransferase)
What does lipoprotein lipase do
degredation of TG circulating in chylomicrons and VLDLs
What does pancreatic lipase do
degredation of dietary TG in small intestine
What does hepatic TG lipase do
degradation of TG remaining in IDL
What does hormone sensitive lipase do
degradation of TG stored in adipocytes
What CETP do
transfers cholesterol from mature HDL to VLDL, IDL and LDL (cholesterol ester transfer protein)
What does apoA 1 do
activates LCAT
What does apoB100 do
binds to LDL receptor, mediates VLDL secretion
What does apoCII do
cofactor for LPL
What does apoB48 do
mediates chylomicron secretion
What does apoE do
mediates extra remnant take up
Delivers dietary TGs to peripheral tissues, delivers cholesterol to liver in the form of remnants, mostly depleted of TGs, secreted by intestinal epith cells
chylomicrons
What apolipoproteins are on chylomicrons
b48, AIV, CII, E
delivers hepatic TGs to peripheral tissue, secreted by liver
VLDL
What apolipoprotiens are on VLDL
B-100, CII and E
Formed and degradation of VLDL, delivers TGs and cholesterol to liver where they are degraded to LDL
IDL
what apolipoproteins are on IDL
B100 and E
Delivers hepatic cholesterol to peripheral tissues, formed by LPL modification of VLDL in the peripheral tissue, taken up by target cells via RME
LDL
What apolipoprotein is on LDL
B100
Mediates reverse cholesterol transport from periphery to liver, acts as respository for apoC an apoE, secreted from both liver and small intestine
HDL
What is the defect in I- hyperchylomicronemia
LPL def, or altered apoCII, elevated TG and cholesterol, causes pancreatitis, hepatosplenomegaly and eruptive/pruritic xannthomas - no risk of atherosclerosis
What is the defect in II A familial hypercholesterolemia
AD absent of dec LDL receptors causes accelerated atherosclerosis, achilles xanthomas and corneal arcus, increase LDL and elecated cholesterol
what is the defectin IV - hypertriglyceridemia
hepatic overproduction of VLDL causing pancreatitis, elvelated TGs and VLDL
How does abetalipoproteinemia present and what is the defect
early in life, AR, inability to synthesize lipoproteins due to def in apoB100 and B48 - intestinal biopsy shows accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons - failure to thrive, steatorrhea, acanthocytosis, ataxia and night blindness
