Biochem 3 USMLE Flashcards by Mani Yavi

NADPH is a procatabolicduct of this pathway

HMP shunt

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NAD+ is generally used in _______ processes to carry reducing equivalents away as NADH

catabolic

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NADPH is used in _____ processes (steroid and fatty acid synthesis) as a supply of reducing equivalents

anabolic

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NADPH is used in these 3 ways:

1) anabolic processes
2) respiratory burst
3) P-450

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where is hexokinase found

throughout the body

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where is glucokinase found

liver

mneu: gLucokinase in Liver

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describe the Km and Vmax of glucokinase in comparison to hexokinase

glucokinase has a lower affinity [higer Km] but higher capacity [ higher Vmax]

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which one hexokinase or glucokinase is feedback inhibited by G6P

hexokinase

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which one hexokinase or glucokinase phosphorylates excess glucose (e.g., after a meal) to sequester it in the liver as G6P

glucokinase

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give the irreversible enzymes in glycolysis regulation

hexokinase/glucokinase
phosphofructokinase-1 (RLS)
pyrovate kinase
pyruvate dehydroginase

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hexokinase/glucokinase converts D-glucose into what?

what is this inhibited by?

Glucose-6-P

Glucose-6-P(inh by product)

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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

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pyrovate kinase converts phosphoenolpyruvate into what?
what is it inhibited by?
stimulated by?

pyruvate

stim: fructose-1,6-BP
inh: ATP, alanine

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pyruvate dehydroginase converts pyuvate into what?

what is it inhibited by?

Acetyl CoA
inh: ATP, NADH
Acetyl-CoA

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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

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why do glycolytic enzyme deficiencies result in hemolytic anemia

RBCs metabolize glucose anaerobically (no mitochondria) and thus depend solely on glycolysis

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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

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Pyruvate dehydrogenase complex is similar to what other complex (same cofactors, similar substrate and action)

alpha ketoglutarate

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give thee pyruvate dehydrogenate reaction.

pyruvate + NAD+ + CoA

-> acetyl CoA + CO2 + NADH

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pyruvate dehydrogenase complex is activated by exercise because it increases these three things

NAD+/NADH ratio
ADP
Ca++

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pyruvate dehydrogenase deficiency causes a backup of substrate which is?

pyruvate and alanine

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pyruvate dehydrogenase deficiency results in this

lactic acidosis

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pyruvate dehydrogenase deficiency is often seen in alcoholics due to a deficiency of this vitamen

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someone with a pyruvate dehydrogenase deficiency may present with this deficit

neurologic

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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

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

in the electron transport cha in 1 FADH gives how many ATP

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)

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

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

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

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

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

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

Apolipoprotein ____ activates lipoprotein lipase

C-II

Apolipoprotein ____ mediates remnant uptake by liver

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

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

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