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
*Pellagra
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)
