Biochem Flashcards
pyruvate dehydrogenase (PDH) complex controls the link between which cellular pathways?
What does PDH do/create?
When is it active/inactive?
glycolysis and the citric acid cycle.
decarboxylates pyruvate (the end product of glycolysis) with production of NADH and acetyl-CoA
PDH complex is active if dephosphorylated by PDH phosphatase and inactive if phosphorylated by PDH kinase
**The kinase and phosphatase are regulated allosterically. The kinase is inhibited by pyruvate and ADP, and activated by acetyl CoA, NADH, and ATP. The phosphatase is activated by calcium
Increased activity of PDH is necessary to break down the large amounts of pyruvate built up in the muscle from glycolysis, and to use the product of that breakdown (acetyl-CoA) in the citric acid cycle
What is hartnup disease?
inheritance pattern?
What do you see in the urine?
Hartnup disease resembles pellagra (“diarrhea, dementia, and dermatitis”) and may be misdiagnosed as nutritional deficiency of niacin.
Auto Rec
Hartnup disease is due to a defect in the epithelial transport of neutral amino acids, including tryptophan, which is a precursor for niacin production
excess amino acid secretion in the urine
Catecholamine synthesis begins with the conversion of tyrosine to dopa by tyrosine hydroxylase, and then dopa to dopamine by dopa decarboxylase.
what enzymes are used to create NE and Epi and in what order?
In the terminal vesicles, dopamine β-hydroxylase converts dopamine to NE
NE is converted to Epi by PMNT using SAM for the methyl group.
PMNT gene is induced by cortisol during times of stress
Child presents with dark blue pigmented nose and ears and urine that turns black upon standing at room temp. disease, deficiency, inheritence
alkaptonuria
deficiency of homogentisic oxidase, leading to accumulation of homogentisic acid.
Homogentisic acid accumulates in the joints and causes degenerative changes.
Accumulation in cartilage imparts a blue-black discoloration (ochronosis)
Homogentisic acid is also excreted in the urine. It undergoes oxidation and is responsible for the urine turning dark.
Citrate acts as an allosteric regulator on 2 enzymes. What are they and which pathways are they associated with?
negative allosteric regulator of phosphofructokinase I, the rate-limiting enzyme and main control point in glycolysis.
positive allosteric regulator of acetyl CoA carboxylase, the rate-limiting and regulated enzyme in fatty acid synthesis.
fibrillary cytoplasm (tissue paper-like)
easy bruising and excessive bleeding
hepatosplenomegaly
pancytopenia
Likely disease and enzyme deficiency?
Gaucher disease
beta-D-glucosidase (glucocerebrosidase) deficiency
Glucosylceramide accumulates in bone marrow, spleen, liver, and lungs, leading to the clinical manifestations of the disease.
The lipid accumulation in the macrophages gives the characteristic Gaucher cell fibrillary “tissue-paper” appearance
Child presents with hepatomegaly, cardiomegaly (often the cause of death), and muscle weakness.
Pompe disease
one of the glycogen storage diseases (Type II), is caused by a deficiency in the lysosomal α-glucosidase enzyme.
Maple syrup urine disease has what inheritance and is characterized by defective breakdown of which amino acids? Potential treatment?
AR
branched chain amino acids (leucine, isoleucine, and valine)
Branched chain alpha ketoacid dehydrogenase requires several coenzymes : Thiamine, Lipoate, Coenzyme A, FAD, and NAD. (Tender Loving Care For Nancy). MSUD pt’s may improve with high dose Thiamine tx but most require lifelong restriction of leucine, isoleucine, and valine.
explain the fate of pyruvate in the presence or absence of oxygen
In presence of oxygen converted to Acetyl-CoA by pyruvate dehydrogenase in mito matrix.
absence of oxygen results in accumulation of NADH which inhibits pyruvate dehydrogenase resulting in pyruvate –> lactate by lactate dehydrogenase. Leads to lactic acidosis.
Lead directly inhibits which enzyme resulting in anemia?
Detla-aminolevulinic acid (ALA) dehydratase
results in anemia, ALA accumulation, and elevated zinc protoporphyrin levels
Neurotoxicity is also a long term complication.
Stem had 18 month old presenting with language regression and low hemaglobin
Severe intellectual disability, hx of seizures, and abnormal pallor of catecholaminergic brain nuclei on autopsy (young) indicate what disease?
PKU
Deficiency of phenylalanine hydroxylase or cofactor tetrahydrobiopterin results in increased phenylalanine. (cant convert phenylalnine into tyrosine)
Acetyl CoA stimulates gluconeogenesis by?
increasing the activity of pyruvate carboxylase
this regulatory step allows pyruvate to be shunted toward acetyl-CoA production when acetyl-CoA levels are low, preventing the cell from becoming depleted of energy
An adult with blue black deposits in connective tissues, sclerae and ear cartilage hyperppigmentation, and osteoarthropathy of the spine/large joints is most likely suffering from what?
Alkaptonuria - Auto recessive - deficiency of homogentisic acid dioxygenase (involved in tyrosine metabolism)
results in excess homogentisic acid which contribute to symptoms
What is the function of Transketolase?
enzyme in non oxidative branch of PPP
responsible in part for interconversion of ribose-5-phosphate and fructose-6-phosphate
After introduction of fructose into diet, infant experiences vomiting and hypoglycemia. Presents with FTT, jaundice, and hepatomegaly. What dz?
Aldolase B deficiency causes hereditary fructose intolerance
