What are the essential amino acid?
PVT TIM HALL. Glucogenic: Met, Val, Arg, His. Glucogenic/Ketogenic: Ile, Phe, Thr, Trp. Ketogenic: Leu, Lys. All essential AA need to be supplied in the diet.
What are the basic amino acids/
Arg, Lys and His. The + charged ones (although His has no charge at body pH).
Walk through the derivatives of Phenylalanine
Phenylalanine => Tyrosine => Dopa (and thyroxine) => Dopamine (and melanin) => NE => E.
Walk through the derivatives of Tryptophan
=(B6)=> Niacin => NAD+/NADP+ AND =(BH4)=> Serotonin => Melatonin
Walk through the derivatives of Histidine
Walk through the derivatives of Glycine
=(B6)=> Porphyrin => Heme
Walk through the derivatives of Arginine
=> Creatinine, => Urea, => Nitric Oxide
Walk through the derivatives of Glutamate
=(B6)=> GABA (via Glutamate Decarboxylase) and => Glutathione
Converts Glutamate to GABA. REQUIRES B6.
Converts Phenylalanine to Tyrosine. Deficient in Phenylketonuria (PKU).
Conerts Tyrosine to DOPA.
Converts DOPA to Dopamine. Requires B6. This is inhibited by Carbadopa!
PKU. Due to a deficiency in phenylalanine hydroxylase, OR a deficiency in tetrahydroblopterin cofactor. Tyrosine becomes an essential amino acid. FIndings: Mental Retardation, Growth retardation, seizures, fair skin, eczema, MUSTY body odor. Tx: Decrease intake of phenylalanine and increase intake of tyrosine. AR
Lack of proper dietary therapy during pregnancy. Findings in infant = microcephaly, mental retardation, growth retardation, congenital heart defects.
Congenital deficiency of Homogentisic Acid Oxidase, in the degradation pathway of Tyrosine. AR. Benign. Findings: DARKNESS: Dark connective tissue, pigmented schlera, urine turns black on standing. May have debilitation arthralgias.
Deficiency of 1 of 3 things: 1. Tyrosinase (cant make melanin). 2. Defective Tyrosine transporters (cant move tyrosine to make melanin). 3. Lack of migration of neural crest cells (lack of melanocytes). INCREASED SKIN CANCER RISK.
3 forms (AR): 1. Cystathionine synthase def. 2. Decreased affinity for cystathionine synthase for pyridoxal phosphate (B6). 3. Homocysteine methytransferase def. Findings: Excess homocysteine, mental retardation, osteoporosis, tall stature, lens subluxation, kyphosis, and atherosclerosis.
Pathway from Methionine to Cystein
Methionine =(SAM and Homocysteine methyltransferase)=> Homocysteine =(B6+Cystathionine synthase)==> Cystathione => Cysteine.
Hereditary defect of renal tubular amino acid transporter for (COLA = Cysteine, Ornithine, Lysine, and Arginine) in the PCT. Leads to cysteine kidney stones. Tx: Acetazolamide.
Maple Syrus Urine disease
Blocked degradation of BRANCHED amino acids (Ile, Leu, Val) due to def of alpha-ketoacid dehydrogenase. Severe CNS defects, death. I Love Vermont maple syrup from maple trees with BRANCHES.
AR disorder characterized by defective neutral amino acid transporter on renal and intestinal epithelial cells. Causes tryptophan excretion in urine and absorption from the gut. Leads to pellagra.
Urea cycle (general)
Amino acid catabolism results in the formation of common metabolites (pyruvate, Acetyl-CoA), which serve as metabolic fuels. Excess nitrogen generated by this process is converted to urea and excreted by the kidneys. Ordinarily, Careless Crappers Are Also Frivolous About Urination.
Carbamoyle Phosphate synthetase I
CPS1. Rate limiting step for the Urea Cycle. Converts CO2 + NH4 into Carbamoyle Phosphate.
Converts Carbamoyle Phosphate into Citrulline. A deficit in this enzyme is a the most common deficiency in the UREA cycle.
Ornithine Transcarbamoylase (OTC) deficiency
Most common urea cycle disorder. X-linked. Interferes with the body's ability to excrete ammonia. Often evident in the first few days of life, but can present with late onset. Excess carbamoyl phosphate is coverted to OROTIC ACID (remember from pyrimidine synthesis). Findings: Orotic Acid in blood/urine, HYPERAMMONEMIA.
Can be acquired or hereditary. Results in excess NH4+, depletes alpha-ketoglutarate, leading to INHIBITION of the TCA cycle. Symptoms = Tremor, Slurring of speech, vomitting, ASTERIXIS (hand flapping tremor). Tx: Limit protein, or give benzoate (for OTC) or lactulose (for liver failure)
A synthetic sugar used in the treatment of constipation andhepatic encephalopathy, a complication of liver disease. Basically causes diarrhea and draws the ammonia out with it.
What is the rate limiting step in fat synthesis?
Acetyl CoA carboxylase, which uses Biotin as a cofactor. Converts Acetyl CoA to Malonyl CoA.
How is Acetyl CoA brought into the cell with fat synthesis?
A citrate shuttle.
What is the rate limiting step of fat degradation?
Carnitine Acyl Transferase. Brings Acyl back into the mitochondria.
Inability to transport Long Chain Fatty Acids into the mitochondria, resulting in toxic accumulation. Causes weakness, hypotonia, HYPOKETOTIC HYPOGLYCEMIA.
Rate limiting step of Cholesterol Synthesis?
HMG-CoA reductase. Converts HMG-CoA to mevalonate. Statins inhibit this.
What are the essential fatty acids?
Linoleic and linolenic acids. Eicosanoids are dependant on essential fatty acids.
Major Apolipoproteins: A-1
Activates LCAT (which catalyzes esterification of cholesterol)
Binds to LDL receptor, mediation VLDL secretion.
Major Apolipoproteins: C-II
Cofactor for lipoprotein lipase (degradation of TG circulating in chylomicrons and VLDL)
Major Apolipoproteins: C-III
Inhibits Lipoprotein lipase (degradation of TG circulating in chylomicrons and VLDL)
Major Apolipoproteins: B-48
Mediation chylomicron secretion
Major Apolipoproteins: E
Mediates EXTRA (remnant) uptake.
Degradation of dietary TG in small intestine
LPL => Degradation of TG circulating in chylomicrons and VLDL
Hepatic TG lipase
HL => degradation of TG remaining in IDL.
Lecithin-cholesterol acyltransferase (LCAT)
Catalyzes esterification of cholesterol.
Delivers dietary TGs to peripheral tissue. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their TG's. Secreted by the intestinal epithelial cells.
Delivers hepatic TG's to peripheral tissue. Secreted by the liver.
Formed in the degradation of VLDL. Delivers triglycerides and cholesterol to the liver, where they are degraded into LDL.
Delivers hepatic cholesterol to peripheral tissues. Formed by lipoprotein lipase modification of VLDL in the peripheral tissue. Taken up by target cells via receptor mediated endocytosis.
Mediates reverse cholesterol transport from periphery to liver. Acts as a repository for apoC and apoE. Secreted from both liver and intestine.
Mediates transfer of cholesterol esters to other lipoprotein particles.
Familial Dyslipidemias: Type 1 hyperchylomicronemia
Increased Chylomicrons, elevated blood TG's and Cholesterol. PATHOPHYS: Lipoprotein lipase deficiency or altered apolipoprotein C-II. Causes pancreatitis, HSM, and xanthomas.
Familial Dyslipidemias: Type IIa Familial hypercholesterolemia
Increased LDL, Elevated Cholesterol. AD. Absent or decreased LDL receptors. Causes accelerated atheroschlerosis, tendon xanthomas, and corneal arcus.
Familial Dyslipidemias: Type IV. Hypertriglyceridemia
Increased VLDL, elevated TGs. Hepatic overproduction of VLDL. Causes pancreatitis.
Hereditary inability to synthesize lipoproteins due to deficiency in apoB-100 and apo-B-48. AR. Findings: Failure to thrive, steatorrhea, acanthocytosis (spiky RBCs), ataxia, night blindness. Tx: Vitamin E.
Mech: Binds FKBP-12 intracellular protein => Inhibition of mTOR => Inhibit T-cell production.
Mech: Affects TNF-alpha Use: Immunosuppression (SLE, organ transplant). Toxic: Phocomelia (flipper limb) in pregnancy.
Mech: Binds to cyclophilins => inhibits calcineurin => prevents production of IL-2. Use: Immunosuppression, organ transplant. Toxic: Predisposes patients to viral infections, lymphoma, and nephrotoxic (prevent with mannitol).
Mech: Like cyclosporn, binds to FK-BP, inhibit secretion of IL-2. Use: Organ transplant (IS). Toxic: Nephrotoxic, peripheral neuropathy, pleural effusion.
Mech: Antimetabolic precursor of 6-MP, that interferes with metabolism and synthesis of nucleic acids. Use: Kidney transplant, autoimmune disorders. Toxic: BONE MARROW SUPPRESION. Increased toxic with allopurinol.
Mech: Mab that binds to CD3, inhibits T-cells. Use: IS after kidney transplant. Toxic: hypersensitivity.
Mech: Inhibits Ionosine Monophosphate Dehydrogenase, prevents guanine synthesis. Use: Immunosuppression., and LUPUS NEPHROPATHY.
Monoclonal antibody with high affinity for IL-2. Immunosuppression.