Biochem 3 USMLE Flashcards
NADPH is a procatabolicduct of this pathway
HMP shunt
NAD+ is generally used in _______ processes to carry reducing equivalents away as NADH
catabolic
NADPH is used in _____ processes (steroid and fatty acid synthesis) as a supply of reducing equivalents
anabolic
NADPH is used in these 3 ways:
1) anabolic processes
2) respiratory burst
3) P-450
where is hexokinase found
throughout the body
where is glucokinase found
liver
mneu: gLucokinase in Liver
describe the Km and Vmax of glucokinase in comparison to hexokinase
glucokinase has a lower affinity [higer Km] but higher capacity [ higher Vmax]
which one hexokinase or glucokinase is feedback inhibited by G6P
hexokinase
which one hexokinase or glucokinase phosphorylates excess glucose (e.g., after a meal) to sequester it in the liver as G6P
glucokinase
give the irreversible enzymes in glycolysis regulation
hexokinase/glucokinase
phosphofructokinase-1 (RLS)
pyrovate kinase
pyruvate dehydroginase
hexokinase/glucokinase converts D-glucose into what?
what is this inhibited by?
Glucose-6-P
Glucose-6-P(inh by product)
phosphofructokinase-1 (RLS) converts fructose 6-phosphate into what?
what is it inhibited by?
stimulated by?
Fructose-1,6-BP
inh by: ATP, citrate
stim by: AMP,Fructose-2,6-BP
pyrovate kinase converts phosphoenolpyruvate into what?
what is it inhibited by?
stimulated by?
pyruvate
stim: fructose-1,6-BP
inh: ATP, alanine
pyruvate dehydroginase converts pyuvate into what?
what is it inhibited by?
Acetyl CoA
inh: ATP, NADH
Acetyl-CoA
Glycolyc enzyme deficiencies such as hexokinase, glucose phosphate isomerase, aldolase, triosephosphate isomerase, phosphate glycerate kinase, enolase, and pyruvate kinase deficiencies are associated with what condition
hemolytic anemia
why do glycolytic enzyme deficiencies result in hemolytic anemia
RBCs metabolize glucose anaerobically (no mitochondria) and thus depend solely on glycolysis
The pyruvate dehydrogenase complex contains 3 enzymes that require 5 cofactors. What are these cofactors.
1) pyrophosphate (B1, thyamine; TTP)
2) FAD (B2, riboflavin)
3) NAD (B3, niacin)
4) CoA (B5, pantothenate)
5. Lipoic acid
Pyruvate dehydrogenase complex is similar to what other complex (same cofactors, similar substrate and action)
alpha ketoglutarate
give thee pyruvate dehydrogenate reaction.
pyruvate + NAD+ + CoA
-> acetyl CoA + CO2 + NADH
pyruvate dehydrogenase complex is activated by exercise because it increases these three things
NAD+/NADH ratio
ADP
Ca++
pyruvate dehydrogenase deficiency causes a backup of substrate which is?
pyruvate and alanine
pyruvate dehydrogenase deficiency results in this
lactic acidosis
pyruvate dehydrogenase deficiency is often seen in alcoholics due to a deficiency of this vitamen
B1
someone with a pyruvate dehydrogenase deficiency may present with this deficit
neurologic
what is the tx for pyruvate dehydrogenase deficiency
increase intake of ketogenic nutrients (e.g., high fat content or high lysine and leucine)
name the only purely ketogenic amino acids
lysine and leucine
how many ATP equivalents are needed to generate glucose from pyruvate
6
this AA serves as a carrier of amino groups form mm to liver
alanine
this can be used to replenish TCA cycle or in gluconeogenesis
oxaloacetate
This cycle transfers excess reducing equivalents from RBCs and mm to liver, allowing muscle to funcction anaerobically (net 2 ATP)
cori cycle
TCA cycle enzymes
Citrate Isocitrate alpha-Ketogluterate Succinyl-CoA Succinate Fumarate Malate Oxaloacetate
mneu: Can I Keep Selling Sex For Money, Officer?
What does the TCA cycle produce per Acetyl-CoA?
how much do we multiply these numbers by if we are dealing with glucose?
3NADH, 1FADH2 2CO2 1GTP 12 ATP
2x w/ glucose
in the electron transport cha in 1 NADH gives how many ATP
3
in the electron transport cha in 1 FADH gives how many ATP
2
name 4 electron transport inhibitors that directly inhibit electron transport, causing a decrease of proton gradient and block ATP synthesis
rotenone, antimycin A, CN-, CO
This ATPase inhibitor directly inhibits mitochondrial ATPase, causing an increase of proton gradient, but no ATP is produceed because electron transport stops
oligomycin
Uncoupling agents like this increase the permeability of the membrane, causing a decrease of proton gradient and increase O2 consumption. ATP synthesis stops. Electron transport continues.
2,4 DNP
irreversible enzymes in gluconeogenesis
pyruvate carboxylase
PEP carboxykinase
Fructose-1,6-biphosphatase
Glucose-6-phosphate
mneu: Pathway Produces Fresh Glucose
pyruvate carboxylase is found here and converts this to this
It requires this
& is activated by this
mitochondria
pyruvate ->oxaloacetate
biotin, ATP
Acetyl-CoA
PEP carboxykinase is found here and converts this to this
It requires this
cytosol
oxaloacetate
->phosphoenolpyruvate
GTP
Fructose-1,6-biphosphatase is found here and converts this to this.
cytosol
fructose-1,6 bisphosphate
->fructose-6-P
where does gluconeogenesis occur
liver, kidney, intestinal epithelium
note: mm cannot participate in gluconeogenesis
deficiency of key gluconeogenic enzymes results in this
hypoglycemia
this dz is caused by a lack of glucose 6 phospatase in the liver
Von Gierke’s
This pathway produces ribose-5-P for nucleotide synthesis
and produces NADPH from NADP+ for fatty acid and steroid biosynthesis and for maintaining reduced glutathione inside RBCs
Pentose Phosphate Pathway (HMP shunt)
All pentose Phosphate Pathway (HMP shunt) reactions occur here
cytoplasm
Is ATP used or produced in Pentose Phosphate Pathway (HMP shunt)
no
give sites of Pentose Phosphate Pathway (HMP shunt)
all sites of fatty acid or steroid synthesis (e.g., lactating mammary glands, liver, adrenal cortex
this is the rate-limiting enzyme in HMP shunt (which yields NADPH)
G6PD
NADPH is necessary to keep this reduced, which in turn detoxifies free radicals and peroxides
glutathione
decreased NADPH in RBCs lead to this due to poor RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine) and antituberculosis drugs
hemolytic anemia
G6PD deficiency is more prevelent amun this racial group
blacks
this sign of G6PD deficiency describes when hemoglobin precipitates within RBCs
Heinz bodies
G6PD deficiency has this inheritance
x-linked recessive
This is a hereditary deficiency of aldolase B (recessive) Fructose-1-phosphate accumulates causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
Symptoms include hypoglycemia,jaundice, cirrhosis, vomiting
fructose intolerance
what is the tx for fructose intolerance
decrease intake of both fructose and sucrose (glucose + fructose)
this d/o involves a defect in fructokinases and is a benign, asymptomatic condition.
Symptoms: fructose appears in blood and urine.
essential fructosuria
essential fructosuria is a deficiency in this enzyme
fructokinase
fructose intolerance is a deficiency in this enzyme
aldolase B
This d/o is an absense of galactose-1-phosphate uridyltransferase. It is autosomal recessive. Damage is caused by accumulation of toxic substances (including galactitol) rather than absense of an essential compound.
Symptoms: cataracts, hepatosplenomegaly, mental retardation
galactosemia
tx of galactosemia
exclude galactose and lactose (galactose + glucose) from diet
this enzyme deficiency causes galactosemia and galactosuria, galactosuria, galactitol accumulation if galactose is present in ddiet.
galactokinase deficiency
this is an age dependent or hereditary intolerance to dairy often seen in blacks and asians. Symptoms include bloating, cramps and osmotic diarrhea.
Tx includes avoiding milk or adding lactase pills to diet
lactase deficiency
give the ketogenic essential amino acids
leucine, lysine
All essential amino acids: PriVaTe TIM HALL
give the glucogenic/ketogenic essential amino acids
Ile, Phe, Trp
All essential amino acids: PriVaTe TIM HALL
give the glucogenic essential amino acids
Met, Thr,Val, Arg, His
All essential amino acids: PriVaTe TIM HALL
which 2 AA are required during periods of growth
Arg
His
what are the acidic amino acids
Asp, Glu
mneu: Asp=aspartic ACID, Glu=glutamic ACID
At body pH (7.4) acidic amino acids (Asp, Glu)are _____ charged
negatively
what are the basic amino acids
arg, lys, his
At body pH (7.4) basic amino acids (Arg, lys)are _____ charged, but _____ has no net charge
positively
his
arg and lys have an extra _____ group
NH3
the MOST basic amino acid
arginine
thise 2 AA are found in high amounds in histones, which bind to negatively charged DNA
arg, lys
this cycle degrades amino acids into amino groups. It accounts for 90% of the nitrogen in the urine.
urea cycle
urea cycle occurs in this organ
liver
in what part of the cell does the urea cycle occur
carbamoyl phosphate incorporation occurs in the mitochondria; the remaining steps occur in the cytosol
urea cycle image p. 94
ornithine, Carbamoyl phosphate, Citrulline, Aspartate, Argininosuccinate, Fumarate, Arginine, urea
mneu: Ordinarily, Careless Crappers Are Also Frivolous About Urination
give the amino acid derivative of epinephrin
phenylalanine
give the amino acid derivative of thyroxine
phenylalanine
give the amino acid derivitive of NAD+/NADP+
tryptophan
give the amino acid derivative of melanin
phenylalanine
give the amino acid derivative of serotonin
tryptophan
give the amino acid derivative of melatonin
tryptophan
give the amino acid derivative of histamine
histadine
give the amino acid derivative of heme
Glycine
give the amino acid derivative of creatine
arginine
give the amino acid derivative of urea
arginine
give the amino acid derivative of nitric oxide
arginine
give the amino acid derivative of GABA
glutamate
give the amino acid derivative of dopamine
phenylalanine
give the amino acid derivative of norepinephnine
phenylalanine
In normal metabolism phenylalanine is converted into _____
tyrosine
in PKU there is decreased ________ or decreased tetrahydrobiopterin cofactor
phenylalanine hydroxylase
findings of phenylketonuria
mental retardation, growth retardation, fair skin, eczema, musty body odor.
mneu: d/o of AROMATIC amino acid metabolism -> musty body ODOR
tx of PKU
no phenylalanine in diet (e.g., aspartame, nutrasweet) and increase in tyrosine
when should you screen for PKU
at birth
name the 3 phenylketones
phenylacetate
phenyllactate
phenylpyruvate
what is the inheratiance of PKU & incidence
autosomal-recessive dz
1:10,000
this is a congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine.
alkaptonuria
in alkaptonuria, these cause the urine to turn black on standing
alkapton bodies
in alkaptonuria, in addition to dark urine this is also dark
connective tissue
pts w/ alkaptonuria may have debilitating
arthralgias
this d/o is a congenital deficiency of either of the follwoing:
1) tyrosinase (inability to synthesize melanin from tyrosine)
2) Defective tyrosine transporters (decrease amounts of tyrosine and thus melanin)
It can result from lack of migration of neural crest cells
albinism
lack of melanine results in an increase risk of this CA
skin CA
this dz results in excess homocysteine in the urine. Cysteine becomes essential. It can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward) and atherosclerosis (stroke and MI
homocystinuria
there are three forms of homocystinuria. Name the enzyme deficiency and give the dietary txs if there is one
1) cytathionine synthase deficiency (tx: decrease Met & increase Cys in diet)
2) decrease affinity of cystathionine synthase for pyridoxal phosphate (tx: increase vit. B6 in diet)
3) Methionine synthase deficiency
This is a common(1:7000) inherited defect of renal tubular amino acid transporter for Cystine, Ornithine, Lysine, and Arginine in kidneys. Excess cystine in urine can lead to the precipitation of cystine kidney stones
Cystinuria
mneu: COLA in the urine
this is a congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine.
alkaptonuria
in alkaptonuria, these cause the urine to turn black on standing
alkapton bodies
in alkaptonuria, in addition to dark urine this is also dark
connective tissue
pts w/ alkaptonuria may have debilitating
arthralgias
this d/o is a congenital deficiency of either of the follwoing:
1) tyrosinase (inability to synthesize melanin from tyrosine)
2) Defective tyrosine transporters (decrease amounts of tyrosine and thus melanin)
It can result from lack of migration of neural crest cells
albinism
tx for Cystinuria
acetazolamide to alkalinize the urine
this dz results from blocked degradation of BRANCHED AA (Ile, Val, Leu) due to decreease alpha ketoacid dehydrogenase. It causes increased alpha ketoacids in the blood, esp Leu. It causes severe CNS defects, mental retardation, and death.
maple syrup urine dz
mneu: urine smells like maple syrup. I Love Vermont maple syrup
tx for Cystinuria
acetazolamide to alkalinize the urine
this dz results from blocked degradation of BRANCHED AA (Ile, Val, Leu) due to decreease alpha ketoacid dehydrogenase. It causes increased alpha ketoacids in the blood, esp Leu. It causes severe CNS defects, mental retardation, and death.
maple syrup urine dz
mneu: urine smells like maple syrup. I Love Vermont maple syrup
what does SCID stand for?
What is the enzyme deficiency?What immune cells are involved?
Who does it effect
Severe combined (T and B) immuodeficiency dz. Adenosine deaminase (ADA)deficiency happens to kids
mneu: bubble boy
pathophysiology of SCID
excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase. This prevents DNA synthesis and thus decreases lymphocyte count.
This dz results from a purine salvage problem owing to absense of HGPRTase, which vonverts hypoxanthine, to inosine monophosphate (IMP) and guanine to guanosine monophosphate (GMP)
Lesch-Nyyhan syndrome
mneu: LNS- Lacks Nucleotide Salvage (purine)
inheratance of Lesch Nyhan syndrome
X-linked recessive.
LNS results in excess of this acid
uric acid
patient manifestation of Lesch-Nyhan syndrome
retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
is the fasting state phosphorylated or non-phosphorylated
phosphorylated
mneu: in the fasting state phosphorylate
this hormone is required for adipose and skeletal mm uptake of glucose
insulin
mneu: INsulin moves glucose INto cells
where is insulin made (cells/organ)
Beta cells of pancreas
what receptors are found in the beta cells
GLUT 2
what receptors are found in mm and fat
GLUT 4
insulin inhibits the release of this hormone by alpha cells of pancreas
glucagon
is serum C-peptide present w/ exogenous insulin intake
no
what are the anabolic effects of insulin
1) glucose transport
2) glycogen synthesis and storage
3) triglyceride synthesis and storage
4) Na+ retention (kidneys)
5) protein sytnesis (mm
Name the tissues that don’t need insulin for glucose uptake
Brain RBCs Intestine Cornea Kidney Liver
mneu: BRICK L
Glucagon ______ (phosphorylates/Dephosphorylates), turns glycogen sytnase _____ and phosphorylase ____
phosphorylates
OFF
ON
Insulin______ (phosphorylates/Dephosphorylates), turns glycogen sytnase _____ and phosphorylase ____
dephosphorylates
ON
OFF
there are 12 types of these diseases all resulting in abnormal glycogen metabolism and accumulation of glycogen within cells
glycogen storage diseases
In this glycogen storage disease, there is a glucose 6-phosphatase deficiency
Von Gierke’s dz (GSD type I)
Give some clinical findings of Von Gierke’s dz (GSD type I)
severe fasting hypoglycemia, increased glycogen in the liver, hepatomegly, increased blood lactate
hint: the liver becomes a mm
In this glycogen storage disease, there is a lysosomal alpha 1,4-glucosidase deficiency
Pompe’s dz (type II)
Give some findings of Pompe’s dz
cardiomegly and systemic findings, leading to early death
mneu: Pompe’s trashes the Pump
heart, liver mm
In this glycogen storage disease, there is a deficiency of debranching enzyme alpha 1,6 glucosidase
Cori’s dz (type III)
give some clinical findings of Cori’s dz
milder form of type I w/ normal blood lactate levels
In this glycogen storage disease, there is a deficiency of skeletal mm glycogen phosphorylase deficiency
McArdle’s dz (type V)
mneu: McArdle’s: Muscle
Give some findings of McArdle’s dz
increased glycogen in mm but cannot greak it down, leading to painful cramps, myoglobinuria w/ strenuous exercise
this classification of dz is caused by a deficiency in one of the many lysosomal enzymes
lysosomal storage diseases
clinical findings are peripheral neuropahty of hands/feet, antiokeratomas, CV/renal dz. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Fabry’s dz
alpha-galactosidase A
Ceramide trihexoside
XR
clinical findings are hepatosplenomegly, aseptic necrosis of femur, bone crises. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Gaucher’s dz
B-glucocerbrosidase
Glucocerebroside
AR
clinical findings are progressive neurodegeneration, HSM, cherry red spot on macula What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Niemann-Pick dz
Sphingomyelinase
Sphingomyelin
AR
mneu:NO MAN PICS (NIEMANN-PICK) his nose w/ his SPHINGER(SPHINGomylenase
clinical findings are progressive neurodegeneration, developmental delay, cherry-red spot, lysozymes w/ onion skin. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Tay-Sachs dz
Hexosaminidase A
GM2 ganglioside
AR
mneu: Tay-SaX (Tay-Sachs) lacks heXosaminidase
clinical findings are peripheral neuropathy, developmental delay, optic atrophy. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Krabbe’s dz
B-galactosidase
Galactocerebroside
AR
clinical findings are central and peripheral demyelination w/ ataxia, dementia. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Metachromatic leukodystophy
Arylsulfatase A
Cerebroside sulfate
AR
clinical findings are developmental delay, gargoylism, airway obsxn, corneal clouding, HSM What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Hurler’s syndrome
alpha-L-iduronidase
Heparan sulfate & dermatan sufate
AR
clinical findings are mild Hurler’s w/ aggressive behavior, no corneal clouding. What is the dz? deficient lysosomal enzyme? Accumulated substrate? Inheritance?
Hunter’s syndrome
Iduronate sulfatase
heparan sulfate, dermatan sulfate
XR
mneu: HUNTERS aim for the X (X-linked recessive)
Where does fatty acid degradation occur
mitochondria
where its products will be consumed
in the liver, fatty acid and amino acids are broken down into ______ to be used by _____ & ______
ketone bodies (acetoacetate + hydroxybuterate To be used in mm & brain).
when are ketone bodies found
prolonged starvation and diabetic ketoacidosis
how are ketone bodies excreted
urine
what are ketone bodies made from
HMG CoA
Ketone bodies are metabolized by the brain to 2 molecules of _______
acetyl-CoA
how do ketone bodies smell on the breath
like acetone (fruity odor)
What is the rate-limiting step in cholesterol synthesis
HMG-CoA reductase, which converts HMG-CoA to mevalonate.
What cholesterol drug inhibits HMG CoA reductase
Lovastatin
2/3 of plasma cholesterol is esterified by this
lecithin-cholesterol acyltransferase (LCAT)
this lipase is responsible for degradation of dietary TG in the small intestine
pancreatic lipase
this lipase is responsible for degradation TG circulating in chylomicrons and VLDLs
lipoprotein lipase
this lipase is responsible for degradation TG remaining in IDL
Hepatic TG lipase
this lipase is responsible for degradation of TG stored in adipocytes
hormone sensitive lipase
this major apolipoprotein Activates LCAT
AI
this major apolipoprotein Binds to LDL receptor
B-100
this major apolipoprotein is a Cofactor for lipoprotein lipase
CII
this major apolipoprotein mediates Extra (remnant) uptake
E
the cells in this part of the body convert FFA back to TG and package it in chylomicrons
intestines
give the 5 lipoproteins
chylomicrons, VLDL, IDL, LDL, HDL
this lipoprotein delivers dietary triglycerides to peripheral tissues and dietary cholesterol to the liver. It is secreted by intestinal epithelial cells. Excess causes pancreatitis, lipemia retinalis, and eruptive xanthomas
chylomicron
Apolipoprotein ____ mediates secetion of chylomicrons
B-48
Apolipoprotein ____ are used for formation of new HDL
A
Apolipoprotein ____ activates lipoprotein lipase
C-II
Apolipoprotein ____ mediates remnant uptake by liver
E
These lipoproteins deliver hepatic triglycerides to peripheral tissues.
VLDL
VLDL is secreted by this organ
liver
excess VLDL causes this dz
pancriatitis
this apolipoprotein mediates secretion of VLDL
B-100
this apolipoprotein mediates remnant uptake of VLDL by the liver
E
this lipoprotein is formed in the degradation of VLDL. It delivers triglycerides and cholesterol to the liver, where they are degraded to LDL
IDL
This lipoprotein delivers hepatic cholesterol to peripheral tissues It is formed by a lipoprotein lipase modification of VLDL in the peripheral tissue. It is taken up by target cells via receptor-mediated endocytosis. Excess causes atherosclerosis, xanthomas, and arcus cornae
LDL
this LDL apolipoprotein mediates binding to cell surface receptor for endocytosis
B-100
This lipoprotein mediates centripetal transport of cholesterol (reverse cholesterol transport, from perhiphery to liver). It acts as a repository for apoC and apo E (which are needed for chylomicron and VLDL metabolism). It is secreted from both liver and intestine
HDL
this HDL apolipoprotein helps form HDL sx
A
this HDL apolipoprotein in particular activates LCAT (which catalyzes esterification of cholesterol)
A-I
this HDL apolipoprotein mediates transfer of cholesterol esters to other lipoprotein particles.
CETP
LDL & HDL carry most cholesterol. ___ transports cholesterol from liver to tissue; ____ transports it from periphery to liver
LDL
HDL
This type of familial dyslipidemia results from a lipoprotein lipase deficiency or altered apolipoprotein CII. It results in increased chylomicrons which leads to elevated blood levels of TG & cholesterol
type I - hyperchylomicronemia
This type of familial dyslipidemia results from a decrease in LDL receptors. It results in an increase of LDL which leads to elevated cholesterol.
type IIa hypercholesterolemia
This type of familial dyslipidemia results from a hepatic overproduction of VLDL leading to an increase in LDL and VLDL leading to elevated TG & cholesterol
type IIb-combined hyperlipidemia
This type of familial dyslipidemia results from altered apolipoprotein E leading to an increase in IDL & VLDL resulting in elevated TG & cholesterol
type III-dysbetalipoproteinemia
This type of familial dyslipidemia results from hepatic overproduction of VLDL resulting in increased VLDL levels leading to elevated TGs in the blood
type IV-hypertriglyceridemia
This type of familial dyslipidemia results from increased production and decreased clearance of VLDL and chylomicrons leading to increased VLDL and chylomicrons resulting in elevated blood levels of TGs & cholesterol
type V-mixed hypertriglyceridemia
