Flashcards in Biochem Deck (76):
I cell disease
Which way do Dynein and kinesin move?
Dynein moves retrograde (+ to -) and kinesin moves anterograde (- to +)
What does ouabain do?
Inhibits the na/k pump by binding to the K+ site
Where does hydroxyl action of collagen occur?
In the RER, specific proline and lysine residues are hydroxylated. Requires vitamin c (deficiency causes scurvy)
Where does glycosylation and the forming of collagen triple helices occur
In the RER. Problems firming this helix lead to osteogenesis imperfect a
What is Menkes disease?
X linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein. Leads to decrease activity of Lysol oxidase
What is RNA interference?
DsRNA is synthesized that is complementary to the mRNA sequence of interest. When transfected into human cells, dsRNA separates and promotes degradation of target mRNA, "knocking down" gene expression
What is special about the inheritance of alpha-1 anti trypsin deficiency
The alleles are co-dominant
What is heteroplasmy?
Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondria lily inherited disease
Enzymes that use thiamine
Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, transketolase, branched-chain ketoacid dehydrogenase
Reactions vitamin B2 is used in
(Riboflavin) Used as cofactors in redox reactions, eg, the succinate dehydrogenase reaction in the TCA cycle
How is niacin made?
Derived from tryptophan. Requires B2 and B6.
How can you get a deficiency of niacin?
Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), and isoniazid (decreased vitamin B6)
What reactions is B5 needed for?
(Pantothenic acid) Essential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase
What is B6 used for?
Converted to pyridoxal phosphate (PLP), a cofactor used in transamination (eg. ALT and AST), decarboxylation reactions, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, histamin, and neurotransmitters including serotonin, epi, norepi, dopamine, and GABA
What is B7 used for?
(Biotin) Cofactor for carboxylation enzymes: pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase
How can you get a deficiency of biotin?
Antibiotic use or excessive digestion of raw egg whites.
What reaction is B12 needed for?
Homocysteine to Methionine (homocysteine methyltransferase) and Methylmalonyl-CoA to Succinyl-CoA (methylmalonyl-CoA mutase [isomerase])
Interaction between Vitamin C and iron
Vitamin C facilitates iron absorption by reducing it to Fe2+ state
What is Vitamin C necessary for?
Hydroxylation of proline and lysine in collagen synthesis; necessary for dopamine beta-hydroxylate, which converts dopamine to NE
Rickets (vitamin D deficiency in children)
Type of anemia in vitamin E deficiency
Lab values in vitamin K deficiency
Increased PT and aPTT but normal bleeding time
Delayed wound healing, hypogonadism, decreased adult hair, dygeusia, anosmia, acrodermatits enteropathica. May predispose to alcoholic cirrhosis
Liver findings in kwashiorkor
Fatty change due to decreased apolipoprotein synthesis
Ethanol to acetaldehyde by alcohol dehydrogenase (in the cytosol); then acetaldehyde to acetate be acetaldehyde dehydrogenase (in the mitochondria)
What is fomepizole
Inhibits alcohol dehydrogenase and is an antidote for methanol or ethylene glycol poisoning
What is disulfiram
Inhibits acetaldehyde dehydrogenase
What is the limiting reagent in ethanol metabolism
What changes does ethanol metabolism cause?
Increases the NADH/NAD ratio in the liver, causing: pyruvate to go to lactate, oxaloacetate to go to malate (preventing gluconeogenesis-> fasting hypoglycemia), and dihydroxyacetone phosphate to of to glycerol-3-phosphate (combines with fatty acids to make triglycerides causing hepatosteatosis). NADH/NAD ratio also disfavors TCA production of NADH causing increased utilization of acetyl-CoA for ketogenesis and lipogenesis
Ethanol can be metabolized in the peroxisome by what enzyme?
Ethanol can be metabolized in the microsome by what enzyme?
CYP2E1 (creates ROS)
What regulates glycogen synthase?
Positive regulation: glucose-6-phosphate, insulin, and cortisol; negative regulation: epinephrine and glucagon
What regulates the HMP shunt
Positive: NADP+, Negative: NADPH
What regulates glycolysis?
Positive: AMP, fructose-2-bisphosphate, Negative: ATP, citrate
What regulates gluconeogenesis?
Positive: ATP, acetyl-CoA; Negative: AMP, fructose-2,6-bisphosphate
What regulates fatty acid synthesis?
Positive: insulin, citrate; negative: glucagon, palmitoyl-CoA
What regulates fatty acid oxidation?
Effect of arsenic on glycolysis
Causes it to produce zero net ATP
When are NAD+ and NADPH used?
NAD+ is used in catabolic process to carry reducing equivalents away as NADH; NADPH is used in anabolic processes as a supply of reducing equivalents
Hexokinase vs glucokinase
Hexokinase- most tissues, low Km (higher affinity), low Vmax (lower capacity), not induced by insulin; glucokinase- liver and beta cells of pancreas, higher Km (lower affinity), high Vmax (higher capacity), induced by insulin
Vomiting, rice-water stools, garlic breath
Arsenic poisoning (arsenic inhibits lipoic acid)
How many ATP are produced per NADH/ FADH2
1NADH=2.5 ATP, 1 FADH2 = 1.5 ATP
What does Rotenone block
Complex 1 of the electron transport chain
What does antimycin A block
Complex III of the electron transport chain
What does oligomycin block?
Complex V of the electron transport chain. An ATP synthase inhibitor. Directly inhibits mitochondrial ATP synthase, causing an increased proton gradient. No ATP is produced because electron transport stops
What blocks complex IV?
Irreversible enzymes of gluconeogenesis
Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase
What does pyruvate carboxylase require? What activates it?
Biotin, ATP. Activated by acetyl-CoA
What does PEP CK require?
What regulates fructose-1,6-bisphosphatase?
Pos: citrate; neg: fructose-2,6-bisphosphate
What is NADPH required for?
Glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis
Where does the HMP shunt take place?
Lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs
What is a copper reaction test?
Nonspecifically detects the presence of reducing sugar
Genetics of essential fructosuria
Autosomal recessive, involves a defect in fructokinase
Autosomal recessive, deficiency of aldolase B. Fructose-1-P accumulates causing a decrease in available phosphate which results in inhibition of glycogenolysis and gluconeogenesis.
Treatment of fructose intolerance
Decrease intake of both fructose and SUCROSE (glucose + fructose)
What may present as a failure to track objects or to develop a social smile?
Galactokinase deficiency, galactitol accumlates, causing cataracts. Autosomal recessive
FTT, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Can lead to E. coli sepsis in neonates
Classic galactosemia, absence of galactose-1-phosphate uridyltransferase, AR
Tx of galactosemia
Exclude galactose and lactose (galactose and glucose) from the diet
Which cells have only aldose reductase?
Schwann cells, retina, and kidneys
What is an alternative method of trapping glucose in the cell?
Converting it to its alcohol counterpart, sorbitol, via aldose reductase (requires NADPH)
What happens to sorbitol?
Some tissues (liver, ovaries, and seminal vesicles) have sorbitol dehydrogenase (requires NAD+) that can convert it to fructose
Diagnosing lactase deficiency
Stool demonstrates decreased pH and breath shows increased hydrogen content with lactose tolerance test. Intestinal biopsy shows NORMAL mucosa
Which amino acids are acidic?
Aspartic acid and glutamic acid
Which amino acids are basic?
Arginine, lysine, histidine
Treatment of pyruvate dehydrogenase complex deficiency?
Increase intake of ketogenic nutrients (e.g., high fate content or increased lysine and leucine)
What are the essential amino acids?
Methionine, valine, histidine (glucogenic). Isoleucine, phenylalanine, threonine, tryptophan (glutogenic/ketogenic). Leucine, lysine (ketogenic)
CO2+NH3 goes to carbamoyl phosphate in the rate limiting step. (Required cofactor: N-acetylglutamate) Then carbamoyl phosphate combines with ornithine to make citrulline. Citrulline + aspartate = argininosuccinate. Fumarate leaves-> arginine. Organize converts this to urea and ornithine
What is the Cori cycle?
Glucose to pyruvate to lactate (moves to liver) to pyruvate to glucose (moves to tissue)