Biochem Flashcards
What does glycerol kinase do?
- in liver and kidney
- degrades glycerol produced by degradation of triglycerides (in adipose tissue) to glycerol-3-P to synthesize glucose during gluconeogenesis
- ex. may raise glucose in DKA
Tetrahydrobiopteran
BH4
Cofactor in synthesis of serotonin, tyrosine, and DOPA
Can lead to phenylketonuria due to inability to break down phenylalanine and tryptophan
Biotin
Acts as CO2 carrier on surface of the carboxylase enzyme. Necessary for conversion of pyruvate to oxaloacetate. Excessive ingestion of egg whites inhibits biotin.
What protein is responsible for the intracellular effects of the G protein mediated adenylate cyclase second messenger system?
Protein Kinase A
Pyruvate Dehydrogenase, a ketogluterate dehydrogenase, and branched chain amino acid dehydrogenase require which five enzymes as cofactors?
(Tender Loving Care for Nancy)
- Thiamine Pyrophosphate (from B1)
- Lipoic Acid
- CoA (from B5)
- FAD (from B2)
- NAD (from B3)
What amino acids can be broken down to form propionyl CoA?
Valine, Isoleucine, Threonine, and Methionine
Propionyl CoA breaks down to eventually become succinylcholine CoA and enter the TCA cycle. Build up of propionyl CoA due to deficiency of propionyl CoA carboxylase leads to prop ionic acidemia.
a-ketoglutarate requires what vitamin as a cofactor to become succinyl CoA?
- thiamine (B1)
- deficient in alcoholics
- rapid glucose admin to alcoholics depletes thiamine in CTA cycle and causes acute wernicke encephalopathy
- thiamine also required for pyruvate dehydrogenase
Alkaptonuria
- AR deficiency of homogentisic acid diozygenase
- disorder of tyrosine metabolism
- prevents conversion of tyrosine to fumarate
- pathway backs up and inc. melanin, leading to black color of urine
- ochronosis of ears, nose, etc
- ochronotic arthropathy manifests in adulthood
Arsenic Poisoning
- mechanism: binds sulfhydryl groups, disrupts cellular respiration and gluconeogenesis
- sources: pesticides/insecticides, contaminated water, pressure treated wood
- manifestations: garlic breath, vomiting, diarrhea, QT prolongation, hypo/hyperpigmentation, hyperkaratosis, stocking glove neuropathy
- tx: dimercaprol, DMSA
Pyruvate Dehydrogenase Complex Deficiency
- AR deficiency in the pyruvate dehydrogrogenase complex
- neurologic sx usually start in infancy, ataxia
- exacerbated in alcoholics due to thiamine deficiency
- tx: inc. intake of high fat foods with ketogenic nutrients (ie. lysine and leucine)
Cysteinuria
- AR
- defective transport of cystine, ornithine, arginine, and lysine (dibasic amino acids) across intestinal and renal tubular epithelium
- may cause nephrolithiasis with hexagonal cystine crystals due to high urinary concentration and inability to reabsorb cystine
- tx: low methionine diet
Gauchers
- AR
- b-glucocerebrocidase deficiency
- accumulated substrate: glucocerebroside
- pancytopenia and hepatosplenomegaly
- tissue paper macrophages
What does urease do?
- splits urea into ammonia and CO2
- lowers acidity (inc. pH)
Homocysteinuria
Presents with lens subluxation, marfanoid habitus, mental disability, and thromboembolic occlusion.
AR dec. in cystathione beta synthase, leading to inc. homocysteine.
Tx: pyridoxine (Bsix) which is a cofactor
Vitamin C is a required cofactor for what processes?
- posttranslational modification of proline and lysine by prolyl hydroxylase and lysyl hydroxylase in the RER
- defective hydroxylation dec. collagen and causes sx of scurvy such as corkscrew hairs, gum bleeding, etc.
Lesch Nyhan
- Defective purine synthesis due to abesnt HGPRT (converts hypoxanthine to IMP and guanine to GMP)
- causes inc. uric acid production
- X linked recessive
- mental retardation, self mutilation, gout,
- tx: allopurinol, or febuxistat (2nd line)
Acute Intermittent Porphyria
- AD
- painful urination, dark urine, urinary incontinence
- anxiety, delerium, agitation
- autonomic nervous system dysfunction
- proximal muscle weakness
- inc. porphobilinogen in cytoplasm due to dec. porphobilinogen deaminase enzyme
Hunter
- lysosomal storage dz
- def. of iduronate sulfatase (leads to inc. heparin sulfate and dermatin sulfate)
- X linked recessive
- developmental delay, aggressive behavior, no corneal clouding
Galactosemia
- absence of galactose-1-phosphate uridyltransferase
- AR
- accumulation of toxic substances (including galacitol in lens of eye)
- failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
- can lead to e. coli sepsis in neonates
- tx: exclude galactose and lactose from diet
Fructose Intolerance
- hereditary deficiency of aldolase B
- AR
- fructose-1-P accumulates
- symptoms present following eating fruit, honey, juice
- urine dipstick neg (tests glucose only)
- hypoglycemia, jaundice, cirrhosis, vomiting
- dec. intake of fructose and sucrose
Reducing Sugar Urine Test
-nonspecific test for inborn errors of carbohydrate metabolism
Trick for remembering enzymes deficient in fructose intolerance and classic galactosemia.
- FAB GUT
- Fructose is to Aldolase B as Galactose is to Uridyl Transferase
Familial Chylomicronemia Syndrome (type 1)
- AR
- protein defect: lipoprotein lipase, apoC-2
- elevated lipoprotein: chylomicron, TG, cholesterol
- sx: acute pancreatitis, lipemia retinalis, eruptive xanthomas, creamy layer supernatent, hepatosplenomegaly
Familial Hypercholesterolemia (type 2a)
- AD
- protein defect: LDL receptor, apoB100
- elevated lipoprotein: LDL, cholesterol
- sx: premature atherosclerosis, tendon xanthomas, xanthelasmas, MI at young age
Familial Dysbetalipoproteinemia (type 3)
- protein defect: ApoE 3 and 4
- elevated lipoproteins: chylomicron and VLDL remnants (IDL)
- sx: premature atherosclerosis, tuberuptive and palmar xanthomas
Familial Hypertriglyceridemia (type 4)
- AD
- protein defect: polygenic
- elevated lipoproteins: VLDL, TG
- hepatic overproduction of VLDL
- sx: coronary dz, pancreatitis (hyperTG), and diabetes, lipemia retinalis, eruptive xanthomas
Xanthelasmas
-cholesterol deposits usually seen on eyelids
Erupting Xanthomas
- subcutaneous depsosits
- commonly seen on tendons
- due to excessive lipids engulfed by macrophages (foam cells)
Things that cause left shift of hemoglobin dissociation curve:
- left shift = inc. O2 affinity
- inc. pH
- dec. temp
- dec. 2, 3-diphosphoglycerate
- right shift is opposite
2, 3, BPG
- high levels cause R shift in heme curve
- fetal hemoglobin has dec. affinity for 2, 3, BPG causing O2 to shift from mother to fetus
What vitamin is a cofactor in transamination reactions?
-vitamin B6 pyridoxine
What amino acid is broken down to serotonin?
-tryptophan
What amino acids are broken down to catecholamines?
- phenylalanine
- tyrosine
Steps to Insulin Release
- glucose enters pancreatic beta cell through glut 2
- glucose is made into ATP
- ATP closes K channel, leading to depolarization of cell membrane
- allows opening of Ca channel
- signals exocytosis of insulin out of cell
- GLP1 receptor also contributes to inc. insulin
Cause of Maternal Onset Diabetes
-dec. function of glucokinase
Most abundant amino acid in collagen?
-Glycine
What do nitrites do to hemoglobin?
- shift Fe2+ to Fe3+ (methemglobinemia)
- Fe3+ binds tightly to cyanide, causes dusky discoloration of skin, and cannot carry oxygen
What are signaling molecules have intracellular receptors?
- cortisol
- cholesterol derived hormones
- TSH
Ornithine and Citrulline are part of what pathway?
-urea cycle of protein degradation
Hormone Sensitive Lipase
- enzyme in adipose tissue that catalyzes stored triglycerides into free fatty acids and glycerol
- in starvation, provides substrates for gluconeogenesis and ketone formation
tRNA
- acceptor stem: 3’ end has CCA tail that amino acid binds to
- D loop: facilitates correct tRNA recognition by aminoacul tRNA synthetase
- anticodon loop: is complementary to mRNA sequence
- T loop: necessary for binding of ribosomes
Fabry
- X linked recessive
- deficiency: a-galactosidase
- accumulated substrate: globotriaosylceramide
- sx: angiokeratomas, peripheral neuropathy, glomerulopathy
Tay Sachs
- AR
- deficiency: B hexosaminidase
- accumulated substrate: GM2 ganglioside
- sx: macular cherry red spot, progressive neurodegeneration
Neimann Pick
- AR
- deficiency: sphingomyelinase
- accumulated substrate: sphingomyelin
- sx: macular cherry red spot, progressive neurodegeneration, hepatosplenomegaly (not seen in tay sachs)
Krabbe
- AR
- deficiency: galactocerebrosidase
- accumulated substrate: galactocerebroside and psychosine
- sx: progressive neurodegeneration, periphary neuropathy, optic atrophy
Metachromatic Leukodystrophy
- AR
- deficiency: arylsulfatase A
- accumulated substrate: cerebroside sulfate
- sx: progressive neurodegeneration, peripheral neuropathy
Hurler
- enlarged skull and abnormally shaped ribs and vertebrae
- corneal clouding
- accumulation of heparan sulfate and dermatan sulfate due to a-L-iduronidase deficiency
