VIOCHEM

pyruvate to lactate (gluconeogenesis)

lactate dehydrogenase (LDH)

During Ethanol oxidation

increase in NAD+ and NADH, lactate production is promoted

pyruvate to oxaloacetate

pyruvate carboxylase In mitochondrial matrix

Deficiency you have: hyperammonemia, INCREASE OF serum alanine + pyruvate

pyruvate carboxylase

Deficiency: liver failure, cardiomyopathy, renal acidosis

Phosphoenolpyruvate carboxykinase (PEPCK)

oxaloacetate to phosphoenolpyruvate

phosphoenolpyruvate carboxykinase (PEPCK)

Glycerol 3 p production promoted

Ethanol oxidation

DHAP to Glycerol 3 p

G-3-P dehydrogenase

Glycerol 3-P to glycerol

Glycerol Kinase

Fructose 1,6-p to Fructose 6p

Fructose 1.6 Bisphosphatase

Deficiency: normal serum transaminase, similar to Type I GSD

Fructose 1.6 Bisphosphatase

Glucose 6p to Glucose

Glucose 6-phosphatase

Deficiency: Type I GSD (Von Gierkes): serum transaminase, lipemia, fasting hypoglycemia (LIVER ONLY)

Glucose 6-phosphatase

galactose to galactose-1-phosphate

galactokinase

Cataracts only ( Non-classical galactosemia)

Deficiency in Galactokinase more Galactose

Cataracts, liver dysfunction, neurological impairment, failure to thrive (Classic galactosemia)

Galactose 1-P uridyltransferase

Galactose-1-P to Glucose-1-P

Galactose 1-P uridyltransferase

Increase of Intracellular Proteins and cataracts in diabetics

Sorbitol

Essential fructosuria (begin/mild)

Deficiency in fructokinase

fructose to fructose-1-phosphate

fructokinase

Hypoglycemia, Lactic acidemia, decreased ATP

Aldolase B (Hereditary Fructose Intolerance)

Aldolase B increase in Fructose 1-P decrease in gluconeogenesis and glycogenolysis

Hereditary Fructose Intolerance

Oxidative stress causes (G6PD deficiency route)

H202 to HO (hemolysis) to Oxidized Hemoglobin (MET HB) to Heinz bodies

Glucose-6-phosphatase to Ribulose 5-P (rate limiting step)

Glucose 6-P dehydrogenase

Decrease Glutathione defense system, decrease NADPH, Dark urine, Increase serum bilirubin, hemolytic anemia

G6PD deficiency

G6PD enzyme deficiency

Glucose 6-P dehydrogenase

Transketolase requires

Thiamine

Thiamine deficiency may effect

Transketolase

Ribose 5-P to Glyceraldehyde 3-P

Transketolase

Xylulose 5-p to Sedoheptulose 7-P

Transketolase

Glycogen with short outter branches, fasting hypOglycemia, hepatomegaly

Type III GSD

Type II GSD enzyme deficient

Debrancher Enzyme B 1,6 Glucoside

Hypoglycemia, Ketosis (Type 0 GSD)

glycogen synthase

myoglobinuria, low glycogen in muscle, exercised induced muscle pain

Type V GSD (McArdles) Muscle only

Mild hypOglycemia, hepatomegaly

Type VI GSD (Hers) Liver only

Type V and VI GSD enzyme deficient

Glycogen Phosphorylase

Glycogen with long outer branches, Hepatosplenomegaly, Hypotonia

Type IV GSD Andersons

Type IV GSD-Anderson Disease

amylo 4,6,transferase branching enzyme

Hepatomegaly, growth failure, fasting Hypoglycemia, lactic academia, Hyperlipidemia

Type I GSD Von Gierkes

Hypoketosis, hypoglycemia, hyperammonemia, cardiomyopathy, skeletal hypotonia decrease in total and free plasma carnitine

AR SLC22A5 gene disorder

Accumulation of VLCFA, and branched chain FA increase level of VLCFA in plasma craniofacial abnormalities, CNS damage, hearing/vision loss, renal cysts

Zellweger syndrome, infantile refsum

AR peroxin gene disorder

Zellweger syndrome, infantile refsum

Adult refsum

impaired alpha oxidation of branched chain fatty acids

Adult refsum results in a accumulation of

phytanic acid

hyperkeratosis, granulosis, acanthosis, CNS Damage, Vision and hearing loss, ichythyosis, ataxia

Adult refsum

decreased ruminant fat, dairy, fish

Treatment to adult refsum

Accumulation of dicarboxylic acids

MCAD deficiency

fasting hypoglycemia, hypoketosis, vomiting, seizures

MCAD Deficiency

CAT deficiency

AR SLC22A5 gene disorder

hypoketosis, hypoglycemia, liver failure, increase total and free plasma carnitine

CPI deficiency

Expressed in the liver and kidney only

CPI deficiency

Hypotonia, cardiomyopathy, arrhythmia or rhabdomyolysis, RF, increase of acylcarnatines, decrease in free serum carnitine

CPII deficiency

jaundice, stones in bile, tea colored urine

Sickle cell crisis

steatorrhea, Vitamin A,D,E,K deficiency

Bile duct blocked

decrease lipase release. decrease TG digestion

Pancreatitis

Inhibitor of pancreatic lipase, weight loss used to decrease fat digestion

orlistat

fat substitute that goes undigested, cannot hydrolyze FAs attached to sucrose

Olestra

Steatosis and steatohepatitis, fibrosis, and cirrhosis

Non-alcoholic fatty liver disease NAFLD

due to insulin resistance/hyperinsulinemia decreased beta oxidation Increased lipogenesis

NON-alcoholic fatty liver disease NAFLD

Lack of surfactant, increase of surface tension = lung collapse

Respiratory distress syndrome

-loss of vision/hearing, muscle atrophy, MACULAR CHERRY RED SPOT

Tay-sachs

Tay-Sachs disease

deficiency in hexosaminidase A, GM2 gangliosides

hepatomegaly, skeletal abnormalities, mental retardation

I-Cell disease

I-cell disease

N-acetylglucosamine 1-P transferase;. lysosomal hydrolases

hepatosplenomegaly, wasting, neurodegeneration

Nieman-Pick A

Nieman Pick A

deficiency in sphingomyelinase and sphingomyelin

spleen, liver, lungs, bone marrow issues

Gaucher

Gaucher disease

Deficiency in B-glucocerebrosidase and glucosylceramide

Increase in APOB100, increased VLDL synthesis = increased TG's in blood

Familial combined Hyperlipidemia

lack of MTP: inability to form chylomicrons and VLDL fatty liver ITGs synthesized, can't export

Abetalipoproteinemia

Decreased cytokine and inflammatory gene exp.

corticosteroids

Inhibition of Phospholipase A decreases formation of

Arachidonic Acid

Luekotriene Modifiers

Blocks LTC4 or LTD4

Increase of isoprostanes

produced by free radicals indication of oxidative stress

reversible competitive inhibition may form stomach ulcers

NSAIDS

COX-2 inhibitors

Decreases PGI2 nut increases TXA2 increases clot risk

defective LDLr= accumulated cholesterol in blood

Familial Hypercholesteremia

Increases (DLU available to bring cholesterol into cells decreases cholesterol levels in blood

PCSK9 inhibitors

Decreases endogenous cholesterol

Statins

decreases dietary cholesterol absorption

Ezetimibe

psychomotor development, mousy/musty urine odor, microcephaly, skin disorders

Classical PKU

Increased phenylalanine =Phenylacetate + Phenylacetate (toxic)

Classical PKU

DHPR deficiency decreased BH4 tetrahydrobiopterin

Nonclassical PKu

photophobia, thick skin on palms, intellectual disability

Tyrosinemia Type II

increase in Tyrosine

Tyrosinemia Type II

homogentiate accumulation/oxidation = dark pigment in urine ochronosis (pigment in skin+ scleral, arthritis)

alkaptonuria

feeding intolerance, high protein causes diarrhea, liver/kidney failure, rickets, early death

Tyrosinemia Type I

Accumulation of Fumarylacetoacetate and deficiency in Fumarylacetoacetate hydrolase

Tyrosinemia Type I

Accumulation of Homogentisate and deficiency in Homogentisate

alkaptonuria

Increase in tyrosine and deficiency in tyrosine aminotransferase

tyrosinemia type II

increase in phenylalanine and deficiency in Hydroxylase

Classical PKU

Protein damage (toxic intermediate)

NAPQI

Increased AST and ALT in blood

diagnostic marker of liver damage

decreased Thiamine Absorption: Deficiency: Degenerative Brain Disease

Wernicke Korsakoff syndrome

sweatiness, shaking, nausea vomiting, and flushing

Acute ROS and Acetaldehyde in blood

irreversible ALDH inhibitor

Disulfiram

Hepatic Steatosis, hyperlipidemia, Ketoacidosis and fasting hypoglycemia, Lactic acidosis and fasting hypoglycemia, Hyperuricemia and gout

Increased NADH and NAD+ from ETOH

Pellagra-like symptoms: Dementia, Diarrhea, Dermatitis, Death

inadequate Niacin or tryptophan decreased NAD

increased NHs, Glutamine, and carbamoyl Phosphate CP floods pyrimidine pathway

OTC deficiency

Increased arginine in the blood

Arginase deficiency