Metabolism — Flashcards

Flashcard 851: Which enzyme is targeted for inhibition in the treatment of Acute Intermittent Porphyria (AIP)? a) ALA synthase b) PBG deaminase

Answer: ALA synthase Acute Intermittent Porphyria (AIP) is caused by a deficiency of **PBG deaminase**, which leads to the accumulation of ALA and PBG. Treatment (such as hemin or high-dose glucose) works by inhibiting **ALA synthase** (the rate-limiting enzyme of heme synthesis) to prevent the further production of these neurotoxic intermediates.

Extra: Hemin provides feedback inhibition of ALA synthase, while glucose/carbohydrates suppress the induction of ALA synthase.

Flashcard 852: 52 y/o woman comes with skin rash that worsens with sun exposure. -Her family says: she has become irritable, hostile, and has had episodes of disorientation. -Further questionning revelas poor nutritional intake and intermittent diarrhea. -Physical Exam: well-demarcated, hyperpigmented, scaly rash on hands, forarms, & upper chest. -Cause of symptoms is due to lack of precursor vitamin for synthesis of NAD+ coenzyme. -This pathway will most likely use which compound as a precursor?

Answer: Tryptophan due to Niacin deficiency ( Diarrhea, dermatitis, dementia)

Flashcard 853: what are the followings in association with 2,6 bisphosphate? -Acetyl COA ---> Fatty acids -Alanine ---> Glucose -Fructose-6-phophate ---> fructose-1,6-bisphosphate -Glucose----> glycogen -NAD ---> NADH

Answer: acetyl coa  ---> fatty acids: It will stimulate this reaction. Also occurs when you have insulin, which causes glucose to enter in cells in order to start glycolysis. glycolysis --> acetyl coa --> fatty acids. -Alanine ---> Glucose: occurs when you have 2,6 bisphosphate. It will inhibit this reaction because it doesn't want glucose present in blood. -Fructose-6-phosphate  ---> fructose-1,6-bisphosphate: It will stimulate this reaction to break down glucose in glycolysis. -Glucose ---> Glycogen: It will stimulate this reaction (similar to insulin) -NAD ---> NADH: It will stimulate this reaction, because of glycolysis.

Flashcard 854: A 54-year-old man presents with anemia. Evaluation shows the cause is EPO deficiency. In this patient, mature erythrocytes are found that are unable to synthesize heme even though they contain detectable levels of cytoplasmic enzymes involved in heme synthesis. Lack of which cellular organelle best explains this phenomenon?

Answer: Mitochondria (Mitochondria play a vital role in heme synthesis; mature erythrocytes lack mitochondria.)

Flashcard 855: 22 y/o comes with 5 day history of Nausea, constipation, and severe, poorly localized abdominal pain. -She also reports anxiety, poor sleep quality and tingling of limbs. -She doesn't take any drugs,no smoking, medication or use alcohol. -Patient receives intravenous infusion of heme preparation that leads to rapid resolution of her symptoms. -The improvement in symptoms is most likely due to treatment-induced downregulation of what enzymes?

Answer: Aminolevulinate synthase (ALA Synthase) which is the rate limiting step in heme synthesis. Patient has Acute intermittent porphyria (recurrent abdominal pain, neuropsychosis symptoms) Symptoms: 5 P's: Port wine urine, polyneuropathy, painful abdomen, psychosis, precipitated by drugs (cytochrome p450) Glucose or heme makes better. (inhibits ALA synthase)

Flashcard 856: What are the followings in relation to gluconeogenesis? -Acetyl CoA -Alanine -Citrate -Fructose 2,6-bisphosphate -Lactate -Oxaloacetate

Answer: - **Acetyl-CoA**: Obligate activator of **pyruvate carboxylase**, shunting pyruvate toward gluconeogenesis. - **Alanine**: Major gluconeogenic amino acid; also **inhibits pyruvate kinase** to prevent glycolysis. - **Citrate**: **Inhibits PFK-1**, which slows glycolysis and favors gluconeogenesis. - **Fructose 2,6-bisphosphate**: Potent inhibitor of gluconeogenesis; **low levels** are necessary for gluconeogenesis to occur. - **Lactate**: Precursor produced in muscles and red blood cells; converted to glucose in the liver (**Cori cycle**). - **Oxaloacetate**: First intermediate of gluconeogenesis; must be shuttled from the mitochondria to the cytosol (via the malate shuttle) to continue the pathway.

Flashcard 857: Which signaling mechanisms or pathways cause an intracellular increase in the following substances? - Ca2+ - cAMP - cGMP - Cl- - mRNA - NO

Answer: • **Ca2+**: Phospholipase C (PLC) pathway (Gq protein) → IP3-mediated release from ER. • **cAMP**: Adenylate cyclase activation (Gs protein). • **cGMP**: Guanylate cyclase activation (e.g., via NO or ANP). • **Cl-**: Activation of GABA-A or glycine receptors (ligand-gated Cl- channels). • **mRNA**: Increased gene transcription (e.g., via steroid hormones or cell division). • **NO**: Synthesis from L-arginine by Nitric Oxide Synthase (NOS).

Flashcard 858: Briefly describe the composition or source of the following carbohydrates: - Amylose - Cellulose - Galactose - Lactose - Maltose - Sucrose

Answer: - **Amylose**: Linear glucose polymer (α-1,4 linkages) found in starch. - **Cellulose**: Glucose polymer (β-1,4 linkages) found in plant cell walls. - **Galactose**: Monosaccharide; component of lactose. - **Lactose**: Disaccharide (Glucose + Galactose); primary sugar found in milk. - **Maltose**: Disaccharide (Glucose + Glucose); product of starch breakdown. - **Sucrose**: Disaccharide (Glucose + Fructose); table sugar.

Extra: - **Fructose Metabolism**: In fructokinase deficiency, some fructose can be metabolized by **hexokinase** to fructose-6-phosphate. In **Aldolase B deficiency** (Hereditary Fructose Intolerance), toxic accumulation of fructose-1-phosphate occurs. - **Galactosemia**: Deficiency in enzymes (most commonly GALT) preventing galactose metabolism. - **Digestion**: Lactose is broken down by lactase; Sucrose by sucrase; Maltose by maltase.

Flashcard 859: 1-day-old boy is diagnosed with hyperphenylalaninemia by newborn screening. - He's placed on a special phenylalanine-restricted diet with tyrosine supplementation. - Several months later, lab test results: normal serum phenylalanine level. - Careful examination: some neurological abnormalities. - Further workup: elevated prolactin. - Physician suspects a cofactor deficiency. - Which enzyme is most likely deficient in this patient?

Answer: Dihydrobiopterin reductase (BH2 reductase) This leads to a deficiency of BH4, which leads to PKU and high prolactin due to lack of dopamine from the same pathway.

Flashcard 860: 11 y/o girl is evaluated for blurry vision. - Physical Exam: bilateral lens opacities -Urine is positive for reducing substances. -Deficient activity of which enzyme is the most likely cause of this patient's eye condition?

Answer: Galactokinase

Extra: Galactokinase deficiency leads to the accumulation of galactose, which is shunted into an alternative pathway where it is converted to **galactitol** by the enzyme **aldose reductase**. Galactitol is osmotically active and accumulates in the lens, leading to cataract formation. Unlike classic galactosemia (GALT deficiency), galactokinase deficiency is relatively mild and typically presents with isolated cataracts and the presence of reducing substances in the urine (galactosuria).