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Flashcards in Biochemestry Deck (41):

Particular feature of arginase deficiency that differentiate from other urea cycle disorders.

Mild or NO hyperammonemia


Functions of tetrahydrobiopterin (BH4)

Cofactor of the most important hydroxylases:
- phenylalanine hydroxylase (tyrosine synthesis, PKU if deficient this enzyme or dihydrobiopterin reductase→synthesis of BH4 [cofactor of phe hydroxylase►malignant PKU→↓↓BH4])
- tyrosine hydroxylase (cathecolamine [from DOPA] synthesis )
- tryptophan hydroxylase (5HT synthesis)
Also for nitric oxide synthase


Ashkenazi Jews show high incidence of what type of metabolic diseases?

Tay-sachs, Niemann-pick, some forms of Gaucher. (Shingolipidoses)


How do you differentiate or identify cori disease from other glycogen diseases, which enzyme is deficient?

- Involve muscle (hypotonia, weakness) and liver (hepatomegaly, fibrosis) ▶️ different of Hers and Von Gierke (also liver involve)
- debranching enzyme deficiency
- hypoglycemia, ketoacidosis, abnormal short outer chain inside hepatocytes


How is the B-oxidation of fatty acids in a high-carbohydrate, high-protein diet? How does that state occur?

- Inhibited
- Malonyl-CoA▶️❌carnitine acyltransferase▶️ fatty acids can not go to the mitochondrial matrix ▶️ no B-oxidation.

- Well-fed state ▶️ ⬆️ ATP ▶️ ❌ isocitrate deshydrogenase ▶️ ⬆️ citrate in mitochondria ▶️(citrate shuttle) cytosol ▶️(ATP citrate lyase) Acetyl-CoA ▶️ Acetyl-CoA carboxylase ➕ by citrate, insulin ▶️ malonyl-CoA►(Fatty acid synthase) Fatty acids


Signs and symptoms of Homocystinuria. 50% of patients respond to which supplementation? Other measures of treatment.

- Marphanoid habitus, ectopia lentis, atherosclerosis, thromboembolic occlusions (MI, stroke), intellectual dissability, osteoporosis, kyphosis.
- High doses of pyridoxine (vitamin B6)
- Restriction methionine if cystathionine synthase deficiency


What is the Zellweger syndrome?

- Deficient or absent peroxisome (member of family Leukodistrophies) ▶️ Infants unable to properly form myelin
- Hypotonia, seizures, hepatomegaly, mental retardation, early death

*More severe of 3, others: Refsum disease, Neonatal adrenoleukodistrophy (NALD)


Cause and mechanism of Refsum disease.

Defect peroxisomal alpha-oxidation ▶️ accumulation of pythanic acid ▶️ neurological disturbances


The first enzyme of the gluconeogenesis converts pyruvate in which component and who regulates that enzyme?

Pyruvate (Pyruvate carboxylase [biotin]) ▶️ Oxaloacetate (in mitocondria)
⬆️ Acetyl-CoA ▶️ ➕ Pyruvate carboxylase ⏩ gluconeogenesis

*⬇️ Acetyl-CoA ▶️ ➕ Pyruvate deshydrogenase ⏩ glycolysis


Markers of Vitamin B12 deficiency

⬆️ Mehylmalonic acid, ⬆️ homocysteine
- cofactor for methylmalonyl-CoA mutase, methyonine synthase


How do you treat an acute intermittent porphyria attack and why? Cause of the disease and what can precipitate the attacks?

- Hemin and Glucose ▶️ 🚫 dALA synthase ▶️ ⬇️ dALA
- Deficiency of Porphobilinogen deaminase (inherited) ▶️ ⬆️ Porphobilinogen (PBG)
- Induction of dALA synthase ▶️ ⬆️ Aminiolevulinate (dALA) [phenobarbital, griseofulvin, phenytoin, alcohol, progesterone - puberty, low-calorie diet]


Which amino acids are useful to treat Pyruvate dehydrogenase deficiency, why? Other measures to treat it?

Lysine or Leucine ▶️ exclusively ketogenic

*Tx: ketone bodies as fuel in placed of Glucose ⏭ ketogenic diet ▶️ high fat, low carb, moderate protein; ketogenic AA. Because:
Glucose ▶️ pyruvate ▶️ ⬆️ lactate ▶️ lactic acidosis


Causes of secondary lactase deficiency

- Infections→ex common: Giardiasis
- Inflammation→ex: celiac disease

*Epithelial destruction and replace by immature cells with low lactase


Which enzymes use as cofactor vitamin B12, and for this reason which components build up in a vitamin B12 deficiency?

- Methionine synthase (⬆️ Homocysteine)
- Methylmalonyl CoA mutase (⬆️ Methylmalonic acid)


Cause and laboratory findings in a Methylmalonic acidemia. Clinical presentation.

- Methylmalonyl CoA mutase deficiency (AR) ▶️ ⬆️ Methylmalonic acid, propionic acid ▶️ metabolic acidosis ▶️ hyperammonemia, hypoglycemia ▶️ ⬆️ ketone bodies (⬆️ anion gap)
- Lethargy, vomiting, hypotonia, tachypnea


In what reaction and by which enzyme of the cycle of krebs is produced the cofactor needed to form phosphoenolpyruvate from oxaolacetate during gluconeogenesis?

Succinyl-CoA ⏩ succinate [succinyl-CoA synthetase or succinate thiokinase] ⤴️ GTP ▶️ needed by phosphoenolpyruvate carboxykinase [oxaloacetate ▶️ PEP]


During starvation what hormone mediates the increase of substrates for gluconeogenesis and ketogenesis?

- Hormone-sensitive lipase (HSL)
- Stress hormones (cortisol, Epi, glucagon)►Gs protein coupled receptor in adipocytes→phosphorylate (PKA)→(+)HSL→lipolysis→release of free fatty acids and glycerol taken by liver
- FFA→acetyl-CoA→ketone bodies or TCA (energy for gluconeogenesis)
- Glycerol→gluconeogenesis


Clinical presentation of Hartnup disease. What vitamin deficiency cause them and why?

- Photosensitivity, pellagra-like symptoms (diarrhea, dementia, dermatitis), ataxia→wax and waine during disease, aminoaciduria (neutral aa)→differentiates from other causes of aminoaciduria (Fanconi syndrome)
- Intestinal and renal absorption of tryptophan (essential aa precursor of nicotinic acid, 5HT, melatonin) is defective→Niacin (B3) deficiency


Causes of vitamin B3 (Niacin) deficiency.
*What is the disease?

- Hartnup disease→↓intestinal and renal absorption of some neutral amino acids, including tryptophan (precursor of niacin)
- Vitamin B6 (pyridoxine) deficiency→ex, Isoniazid►B6 needed to synthesis of niacin from Trp
- Malignant carcinoid syndrome→↑metabolism of Trp
- Dietary→↓intake Trp, Lysine, ↑intake leucine



Most common enzymes deficiencies of the B-oxidation and clinical presentation

- Acyl-coA dehydrogenase deficiency▶️most common⏩hypoketotic hypoglycemia after fasting (⬇️⬇️acetoacetate in blood)
- Primary carnitine deficiency▶️fatty acids not transported to mitochondria⏩muscle weakness, cardiomyopathy, ⬆️muscle triglycerides, hypoketotic hypoglycemia


Causes of galactosemia

- GALT deficiency
- GALK deficiency
- UDP-galactose-4 epimerase


Cause and consequence of glactose-1-phosphate accumulation

- Galactose-1-phosphate uridyl transferase (GALT) deficiency
- Toxic accumulation→liver dysfunction►transaminitis, hyperbilirrubinemia, hypoglycemia; renal dysfunction►hyperchloremic metabolic acidosis, aminoaciduria; predisposition to E. coli sepsis; cataract►galactitiol accumulation in lens


Treatment of GALT deficiency

Replace breast milk by soy milk (glucose+fructose)


Effect of ethanol on gluconeogenesis and why does it occur?

Ethanol▶️⬆️NADH, ⬇️NAD (alcohol dehydrogenase and aldehyde dehydrogenase reduces NAD to NADH)▶️NAD is require for gluconeogenesis:
- ❌Lactate▶️pyruvate (intermediate of gluconeogenesis)
- ❌Malate▶️Oxaloacetate (intermediate of gluconeogenesis)


What is produced during the oxidative irreversible stage of pentose phosphate pathway and its functions?

NADPH (main source)▶️cholesterol (steroids) and fatty acid synthesis, glutathione antioxidant mechanism


Important products of nonoxidant (reversible) stage of pentose phosphate pathway and its functions.

- Ribose 5-phosphate▶️nucleic acid synthesis
- Fructose 6-phosphate (others glucolytic intermediates)▶️glycolysis


What is the useful of urine copper reduction test?

Detection of reducing sugars in urine (galactose, fructose, glucose)▶️nonspecific for inborn errors of carbohydrate metabolism


Which mechanism do TNF-alpha, glucagon, catecholamines and corticoids use to induce insulin resistance?

➕Serine kinases▶️phosphorylation at serine residues on beta subunits of insulin receptor (IR) and on insulin receptor substrate (IRS)→🚫normal tyrosine phosphorylation of them▶️⬇️insulin downstream signaling


From lipolysis which substrate may be used to produce glucose (gluconeogenesis) and what enzyme initially allow that?

Triglycerides→Glycerol+fatty acids→glycerol to liver (glycerol kinase)→glycerol 3-phosphate (glycerol 3-phosphate dehydrogenase)→DHAP►glucose


Which tissues cannot use ketone bodies as source of energy?

- Erythrocytes▶️lack mytochondria
- Liver▶️lack succinyl CoA acetoacetate CoA transferase (thiophorase) (acetoacetate▶️acetoacetyl Coa)

*Skeletal muscle, cardiac muscle (both primarily consumed KB to preserve Glc for brain), brain (prolonged starvation), kidney


How is activated the phosphorylase kinase at skeletal muscle and liver and what is the result of it?

- Liver: Epinephrine, glucagon▶Gs protein-coupled receptor▶⬆cAMP▶➕PKA▶➕phosphosrylase kinase (PK)➡glycogenolysis▶maintain blood glucose levels during fasting state
- Skeletal muscle: Ca release from sarcoplasmic reticulum▶➕PK➡glycogenolysis▶energy necessary for anaerobic muscle contraction (synchronization with contraction)


Which feature of elastin explains its rubber like properties?

Lysyl oxidase (requires copper)→oxidatively deaminates lysine residues to tropoelastin→formation of demosine cross-links between neighboring polypeptides


What supplementation do you use to treat maple syrup disease and why?

Thiamine→one of the cofactors of branched-chain α-ketoacid dehydrogenase
*Also dietary restriction Leucine, Isoleucine, Valine


What have in common branched-chain α-ketoacid dehydrogenase, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase?

Need same cofactors:
Thiamine, Lipoate, Coenzyme A, FAD, NAD
"Tending Loving Care For Nancy"


What is the most abundant amino acid in collagen? What is the function of the other common amino acids?

- Glycine→most common
- Proline→essential for alpha-helix formation
- Hydroxylysine→need for cross-linking


What disease is caused by defect in phosphorylation of manose in a newborn with coarse facial features, skeletal abnormalities (congenital dislocation of hip), psycomotor abnormalities? Pathogenesis.

- I-cell disease (inclusion cell disease/mucolipidosis type II)
- Defect in N-acetylglucosaminyl-1-phosphotransferase→failure of the Golgi to phosphorylate mannose residues (↓mannose-6-phosphate) on glycoproteins→proteins are secreted
extracellularly rather than delivered to lysosomes


What sphingolipid disease has both peripheral neuropathy and progressive neurodegeneration? what other feature depict that disorder?. Mention enzyme deficiency and substrate that build up.

- Krabbe disease→↓Galatocerebrosidase→↑Galactocerebroside
- Optic atrophy, globoid cells


Treatment for orotic aciduria

Uiridine phosphate supplementation→bypass mutated enzyme (UMP synthase)


Cause of alkaptonuria. Clinical presentation.

Deficiency Homogentisate oxidase (or deoxygenase)→↑↑Hogentisic acid (Tyrosine metabolism to fumarate→TCA)
- Ochronosis→bluish-black connective tissue, ear cartilage, sclera
- Urine turns black after prolongued exposure to air
- Debilitating arthralgias→Ochronotic arthropathy


Extracellular processing of collagen

- N and C terminal cleaving by procollagen peptidases→procollagen►Tropocollagen (less soluble)
- Tropocollagen monomers self-assemble into collagen fibrils
- Lysyl oxidase→covalent crosslinks between collagen fibrils►strong collagen fibers


What is the role of the IkB in the activation of NF-kB and the pathway by which it can occur?

- IkB normally bind and mantain in cytoplasm the NF-kB►phosphorylation of IkB (target to proteasome) release NF-kB→nucleus as a transcription factor
- Cytokines (IL-1) and TNF-alpha receptors pathway→(+) IKK comples→phosphorylation of IkB