BIOCHEM Flashcards
What are some causes of cobalamin deficiency?
Cobalamin deficiency may occur with:
- Malabsorption (e.g. Diphyllobothrium latum, sprue, enteritis)
- Absence of intrinsic factor (e.g. pernicious anemia or gastric bypass surgery)
- Absence of terminal ileum (due to Crohn disease or resection)
- Vegan diet
What two conditions can lead to vitamin E deficiency and what are the signs?
Vitamin E deficiency is rare and primarily occurs in:
- children with cystic fibrosis (due to fat malabsorption secondary to decreased bile salts and pancreatic insufficiency)
- abetalipoproteinemia (fat malabsorption)
Signs are hemolytic anemia, peripheral neuropathy, posterior column degeneration, retinal degeneration, and myopathy. Vitamin E deficiency signs can mimic those of vitamin B12 deficiency, but vitamin E deficiency is without increased methylmalonic acid levels or megaloblastic anemia.
What protein is insulin first synthesized as and where does this occur?
Insulin is first synthesized as preproinsulin in the rough endoplasmic reticulum
What is the second reaction of basic alcohol metabolism? Where does it take place?
Acetaldehyde enters the mitochondria and is oxidized by acetaldehyde dehydrogenase (ALDH) to form acetate and NADH.
What are the main functions of Vitamin A?
Vitamin A: functions as a component of visual pigments and in cell differentiation
Thiamine deficiency results in which 2 syndromes?
A vitamin B1 (thiamine) derivative, thiamine pyrophosphate (TPP), is an important coenzyme for several reactions. some of which can be remembered with the mnemonic, ATP:
α-ketoglutarate dehydrogenase
Transketolase
Pyruvate dehydrogenase
Vitamin B1 is also a cofactor for branched-chain ketoacid dehydrogenase.
Vitamin B1 (thiamine) most often plays a role in decarboxylation of α-keto acids.
In the United States, thiamine deficiency is most common in alcoholics (due to poor nutrition and that excess alcohol limits the body’s ability to absorb and store thiamine.)
Thiamine deficiency may lead to beriberi (“Ber1Ber1”) and Wernicke-Korsakoff syndrome.
Beriberi has a dry (muscle wasting and neuropathy) and wet (dilated cardiomyopathy) component.
Wernicke-Korsakoff syndrome is composed of Wernicke’s encephalopathy (triad of confusion, ophthalmoplegia, and ataxia) and Korsakoff’s psychosis (memory loss, confabulation and personality change).
In what cells is glucagon predominantly synthesized?
Glucagon is cleaved from a larger peptide chain inpancreatic α-cells of the islets of Langerhans.
Excess intake of what vitamin can decrease the efficacy of L-DOPA therapy in Parkinson’s disease?
A core treatment in Parkinson’s disease is L-DOPA therapy. Supplemental vitamin B6 can convert L-DOPA to dopamine peripherally (as opposed to in the CNS), rendering treatment less efficacious.
Why do alcoholics develop hypoglycemia?
Pyruvate and oxaloacetate depletion leads to inhibition of gluconeogenesis and stimulation of fatty acid synthesis, which results in fasting hypoglycemia.
What are the signs of pyridoxine deficiency?
Pyridoxine deficiency causes:
- Neurological pathology: Peripheral neuropathy and convulsions (due to defective neurotransmitter synthesis).
- Anemia: Sideroblastic anemias due to defective heme synthesis.
What is the function of folate?
Folate is converted to tetrahydrafolate (THF), which is a carbon carrier critical for synthesis of nitrogenous bases (particularly thymine, adenine, and guanine) in nucleic acids, especially in states of rapid cell division (pregnancy, erythropoiesis).
What are three pathologies of vitamin D deficiency?
Vitamin D deficiency causes:
- Rickets in children (imperfect calcification, softening, and distortion of the bones classically resulting in bowed legs)
- Osteomalacia in adults (soft bones and bone pain).
- Hypocalcemic tetany (decreased extracellular calcium levels cause increased excitability of voltage gated sodium channels, leading to increased muscle contractions)
What are the key signs of acute vitamin A toxicity?
Acute vitamin A toxicity causes:
- Nausea
- Vomiting
- Visual disturbances
- Vertigo
What vitamin deficiency may be seen in carcinoid syndrome?
Carcinoid syndrome is a complication of carcinoid tumors (most commonly of the small bowel) in which serotonin is systemically elaborated in great excess. Tryptophan is compensatorily shunted to make serotonin, decreasing conversion to niacin. Therefore,niacin deficiency is a potential complication of carcinoid syndrome.
In what general class of hormones is glucagon?
Glucagon is a 29 amino-acid peptide hormone.
Which B vitamin generally plays a role in the decarboxylation of α-keto acids?
Vitamin B1 (thiamine) most often plays a role in decarboxylation of α-keto acids.
A vitamin B1 (thiamine) derivative, thiamine pyrophosphate (TPP), is an important coenzyme for several reactions. some of which can be remembered with the mnemonic, ATP:
- α-ketoglutarate dehydrogenase
- Transketolase
- Pyruvate dehydrogenase
Vitamin B1 is also a cofactor for branched-chain ketoacid dehydrogenase.
Vitamin B1 (thiamine) most often plays a role in decarboxylation of α-keto acids.
What is the pathophysiology of the edema seen in kwashiorkor?
Decreased protein consumption leads to decreased protein production. Because of the decreased protein production the capillary oncotic pressure decreases and this leads to tissue edema in kwashiorkor. The following mnemonic might be useful: You need water to wash → kwashiorkor has excess water (edema).
What two important pathways are activated by IRS-1?
- Insulin exerts its effect by binding to the extracellular domain of an intrinsic tyrosine kinase receptor.
- The activated intracellular domain of the tyrosine kinase receptor phosphorylates the insulin receptor substrate-1 (IRS-1) protein.
- IRS-1 plays a key role in insulin signal transduction by activating the Phosphoinositide-3 kinase (PI-3 kinase) pathway and the MAPK pathway.
PI-3 Kinase Pathway
- The PI-3 kinase pathway is responsible for the fusion of vesicles containing the GLUT4 transporter into the membrane of myocytes and adipocytes.
- Thus, the PI-3 pathway leads to increased glucose uptake by myocytes and adipocytes. Additionally, PI-3K is involved in upregulation of glycolysis, as well as glycogen and lipid synthesis.
MAPK Pathway
- The MAPK pathway regulates the expression of genes that increase cell growth and DNA synthesis.
Finally, the insulin signal is terminated when the insulin-receptor complex is endocytosed and degraded.
What is the toxic byproduct of ethylene glycol metabolism? What specific organ damage may be seen in toxicity?
Ethylene glycol is metabolized to oxalic acid (via alcohol dehydrogenase and several subsequent reactions).
Oxalic acid combines with metal ions to deposit crystals in kidney tubules, leading to metabolic acidosis and acute renal failure.
Why are infants are given a vitamin K injection at birth to prevent hemorrhagic disease of the newborn?
Since vitamin K is synthesized by intestinal flora and neonatal intestines are not yet colonized by bacteria, infants are given a vitamin K injection at birth to prevent hemorrhagic disease of the newborn.
What is the primary stimulus for insulin release?
Increased glucose concentration inside β-cells is the primary stimulus for insulin release.
Name a vitamin that, when taken in excess, can synergistically act with warfarin.
Excess (taking megadoses of vitamin E): decreased synthesis of vitamin K-dependent coagulation factors in the liver, thereby working synergistically with warfarin.
What is lacking in the diet of a child with marasmus? Contrast this with the malnutrition that results in kwashiorkor.
In contrast to kwashiorkor, which is caused by insufficient protein intake despite adequate calories,marasmus (from Greek meaning “dying away” or “withering”) results from inadequate protein and overall calories.
How is breastfeeding implicated in the onset of kwashiorkor in some parts of the world?
In some areas, kwashiorkor presents between ages 1-3 when a child that received enough protein while breastfeeding is displaced by a new child.
What is the end result of PI-3 kinase pathway activation in insulin signaling?
The PI-3 kinase pathway is responsible for the fusion of vesicles containing the GLUT4 transporter into the membrane of myocytes and adipocytes. Thus, the PI-3 pathway leads to increased glucose uptake by myocytes and adipocytes. Additionally, PI-3K is involved inupregulation of glycolysis, as well as glycogen and lipid synthesis.
What is the first reaction of alcohol metabolism in nonalcoholics? Where in the cell does it take place?
In the cytosol, ethanol is oxidized by alcohol dehydrogenase (ADH) to form acetaldehyde and NADH. The limiting reagent is NAD+. ADH works via zero-order kinetics.
Describe the role of ascorbic acid in collagen synthesis.
Vit C serves as a cofactor for prolyl-4-hydroxylase and lysyl hydroxylase, an enzyme involved in collagen synthesis.
What is the structure of insulin?
Insulin is a peptide hormone consisting of an A chain and a B chain linked by two disulfide bonds.
A 37-year-old woman, who works as a financial analyst, is prescribed disulfiram for alcohol abuse. After a particularly difficult day at work, she has 2 alcoholic drinks and develops severe nausea, flushing, and a headache. Which metabolite is responsible for her symptoms?
A Acetate
B Formic acid
C Acetaldehyde
D Ethanol
E Formaldehyde
ANSWER + EXPLANATION
Disulfiram inhibits acetaldehyde dehydrogenase, causing an accumulation of acetaldehyde, the first product of ethanol metabolism. The accumulation of acetaldehyde causes vomiting, headache and marked vasodilation, which manifests as flushing and sweating.
ANSWER C
What are three conditions that can cause fat-soluble vitamin deficiency?
Vitamins A,D,E,K are fat soluble vitamins that are transported in chylomicrons, and stored in liver or adipose tissue.
fat-soluble vitamins are more likely to reach toxic levels than water-soluble vitamins
deficiencies of fat soluble vitamins can occur any time fat malabsorption occurs, for example:malabsorption syndromes (e.g. tropical sprue), pancreatic insufficiency, and resected ileum.
What are the key clinical findings of chronic vitamin A toxicity?
Chronic vitamin A toxicity causes:
Hepatoxicity
Hepatomegaly
Dry skin
Alopecia
Arthalgia
Pseudotumor cerebri
What is the result of ATP dependent closure of potassium channels on membrane potential in pancreatic β cells?
Closure of these potassium channels leads to membrane depolarization.
In which organ is calcidiol produced?
Next, vitamin D is hydroxylated in the liver to produce calcidiol (25-hydroxycholecalciferol) by the P450 system.
Name 2 enzymes for which cobalamin is a cofactor.
Vitamin B12 (cobalamin) is a cofactor for:
Methylmalonyl CoA mutase, which converts methylmalonyl CoA to succinyl CoA
Homocysteine methyltransferase, which transfers methyl groups to homocysteine to form methionine
A physician misdiagnoses a vitamin B12 deficient patient with folate deficiency and instructs the patient to take folate supplements. Will the patient’s symptoms be relieved?
The hematologic symptoms of B12 deficiency can be corrected by folate replacement, e.g., in the case of a misdiagnosis. However, the neurological symptoms will persist due to methylmalonic acid buildup in the myelin sheaths.
Note: The metabolism of methylmalonic acid requires B12, not folate.
What is the primary distinguishing symptom between kwashiorkor and marasmus?
Kwashiorkor and marasmus are distinguished symptomatically primarily by edema. Patients with kwashiorkor are edematous. Patients with marasmus tend not to have edema.
In chronic alcoholics, what class of enzymes are inhibited by the increased NADH/NAD+ ratio?
The NADH generated from basic alcohol metabolism increases the NADH/NAD+ ratio, which inhibitsdehydrogenase reactions, leading to acute and chronic alcohol toxicities.
What are the signs of scurvy?
Signs of scurvy include:
- Swollen, spongy and purplish gums that bleed often
- Bleeding into the skin (bruising)
- Red spots under skin from burst capillaries (petechiae)
- Loose teeth
- Bulging of the eyes (proptosis)
- Anemia
- Dry, brittle hair that curls (“corkscrew” hair)
- Slow wound healing
- Bleeding into the joints (hemarthrosis) and muscles, which causes swelling over the bones of the arms and legs
Which vitamin is a cofactor for carboxylation reactions? What are three important carboxylation reactions that use this vitamin cofactor?
Vitamin B7 (biotin): cofactor in several carboxylation reactions including:
- Acetyl-CoA carboxylase: converts acetyl-CoA (2C) to malonyl-CoA (3C) in fatty acid synthesis
- Pyruvate carboxylase: converts pyruvate (3C) to oxaloacetate (4C) in gluconeogenesis
- Propionyl-CoA carboxylase: converts propionyl-CoA (3C) to methylmalonyl-CoA (4C) in the metabolism of odd-chain fatty acids
What drug inhibits alcohol dehydrogenase and is used as an antidote for methanol or ethylene glycol poisoning?
Fomepizole inhibits alcohol dehydrogenase (ADH) and is used as an antidote for methanol or ethylene glycol poisoning.
Which lab test can be used to distinguish B12 and folate deficiency?
Serum methylmalonic acid (MMA). Sensitive test for B12 deficiency. Can be used to differentiate folate and B12 deficiency. MMA levels (reference range 70-270 mmol/L) are elevated in B12 deficiency only.
What is kwashiorkor?
Kwashiorkor is malnutrition with inadequate protein but adequate calories.
An intracellular increase in which mineral results in exocytosis of insulin secretory vesicles?
Increased intracellular [Ca2+] leads to exocytosis of insulin secretory vesicles, causing increased insulin in the blood.
Which nucleotide is not dependent on folate for synthesis?
A Cytosine
B Adenine
C Thymine
D Guanine
Cytosine
Answer Explanation
Folate is needed for thymine and purine synthesis. Purines = adenine and guanine.
A 25-year-old female is seen in clinic 2 years following successful bariatric surgery. She has lost 140 pounds from a preoperative weight of 250 pounds. Upon referral for body contouring surgery, it is discovered that she has recently had several weeks of hair loss and diarrhea despite no change in her diet. Which deficiency does she most likely have?
A Ascorbate
B Riboflavin
C Zinc
D Biotin
E Pantothenic acid
C
Answer Explanation
Although zinc and biotin deficiency can both lead to alopecia, biotin deficiency is very rare, whereas zinc deficiency is relatively common in patients with malabsorption (e.g. s/p bariatric surgery or sprue). Moreover, biotin deficiency is not known to cause diarrhea, whereas diarrhea is a common feature of zinc deficiency.
A 9-year-old child is brought to the ER after the mother found him drinking from the antifreeze solution tank. The child complains of abdominal pain and a urinalysis reveals the finding shown here. Which of the following would be used to treat this type of poisoning?
A Disulfiram or Fomepizole
B Pencillamine
C Dimercaprol
D N-Acetylcystine
E Ethanol or Fomepizole
E Ethanol or Fomepizole
Answer Explanation
Ethylene glycol (antifreeze) poisoning can result in precipitation of oxalic acid - calcium crystals in the glomeruli, which can cause renal failure. The treatment is to use ethanol as a competitive inhibition substrate product for alcohol dehydrogenase. Instead of metabolizing ethylene glycol, alcohol dehydrogenase will metabolize ethanol and produce a less toxic acetaldehyde byproduct. Fomepizole can also be used to inhibit alcohol dehydrogenase. N-acetylcysteine is used to treat acetaminophen liver toxicity. Dimercaprol is used to chelate Arsenic, Gold, Mercury, Copper or Lead. Penicillamine is used to chelate lead poisoning or conditions such as hemochromatosis.
Deficiency of ascorbate leads to what disease?
Deficiency of vitamin C leads to scurvy due to defective collagen synthesis.
What are two molecules that are derived from riboflavin?
Vitamin B2 (riboflavin): key component of FAD (used in succinate dehydrogenase of the TCA cycle, aka complex II of the electron transport chain) and FMN (used in NADH dehydrogenase, aka complex I of the electron transport chain), which are used as cofactors for redox reactions.
What are some sources of vitamin D?
Sources of vitamin D include:
Liver
Egg yolk
Saltwater fish
Vitamin D fortified foods (milk)
Vitamin D3 is made by skin after sunlight exposure (although some foods are now fortified with synthetic D3).
Why must a woman have a pregnancy test before taking high doses of Vitamin A?
Before oral isotretinoin (cis retinoic acid) is prescribed for severe cystic acne, women must have a pregnancy test because high doses of Vitamin A are highly teratogenic (birth defects include cleft palate, cardiac abnormalities, low IQ scores and extremely high risk for spontaneous abortions)
What type of receptors does glucagon bind to?
Glucagon binds to the extracellular side of a G-protein coupled receptor.
What is the etiology of pellagra in the setting of carcinoid syndrome?
A Inflammatory process
B Neoplastic process
C Autoimmune destruction
D Thiamine toxicity
E Nutrient deficiency
E Nutrient deficiency
Answer Explanation
Pellagra occurs in the setting of niacin deficiency. Niacin is made from tryptophan. In carcinoid syndrome, serotonin is produced in excess amounts, which consumes the precursor of serotonin: tryptophan. Recall that niacin biosynthesis requires tryptophan, thus carcinoid syndrome can lead to pellagra.
What type of liquor can be a source of methanol poisoning? What is the first (toxic) byproduct of methanol metabolism?
Moonshine (illicitly produced liquor) can be contaminated by methanol, a highly toxic alcohol that is metabolized to formaldehyde.
How does the first phase of insulin release differ from the second phase of insulin release?
Insulin release occurs in two phases:
1st phase is rapid and comes from insulin that has already been synthesized and stored
2nd phase of insulin release is dependent on new synthesis of insulin
What are three important medical uses for vitamin A?
Medical uses:
- Tretinoins (all-trans retinoic acid, acid form of vitamin A), which is a topical medication used for mild acne and psoriasis
- APML (acute promyelocytic leukemia, aka M3 subtype of AML) to induce maturation of leukemic cells.
- Measles (specifically used in malnourished children to prevent exfoliative dermatitis)
Name 3 signs/symptoms that result from biotin deficiency.
Biotin deficiency causes:
Dermatitis
Alopecia
Enteritis
After insulin binds its tyrosine kinase receptor, what intracellular protein is phosphorylated?
The activated intracellular domain of the tyrosine kinase receptor phosphorylatesthe insulin receptor substrate-1 (IRS-1) protein.
Via what signalling cascade is the glucagon signal amplified?
The signal is amplified through an adenylyl cyclase → cAMP → Protein Kinase A pathway.
What are the three treatment stages for severe energy malnutrition?
he treatment of severe energy malnutrition consists of an initial stabilization phase (first week), followed by a rehabilitation phase (two to six weeks), and a follow-up phase.
A 34-year-old woman is prescribed an antagonist of vitamin K epoxide reductase. This class of medication functionally makes her vitamin K deficient. Which protein is least affected by this medication?
A Protein S
B Factor VIII
C Factor X
D Factor II
E Protein C
B Factor VIII
Answer Explanation
Vitamin K epoxide reductase reduces vitamin K after it has been oxidized by carboxylation reactions that are required in the synthesis of factors II, VII, IX, X, and proteins C and S. Any form of vitamin K deficiency will reduce levels of those proteins, but doesn’t affect factor VIII.
What are 2 etiologies of biotin deficiency?
Although relatively rare, biotin deficiency can be caused by antibiotic useor excessive consumption of raw egg whites, which can be seen in individuals who are bodybuilders or boxers (e.g., Rocky Balboa).
Where is insulin stored until release?
Insulin and C-peptide are stored in secretory granules until exocytosis is stimulated.
What class of receptor is the insulin receptor?
Insulin exerts its effect by binding to the extracellular domain of anintrinsic tyrosine kinase receptor.
What are the signs of vitamin A deficiency?
Deficiency: night blindness, squamous metaplasia leading to skin abnormalities (follicular hyperkeratosis), eye abnormalities (Bitot’s spots → buildup of keratin debris in conjuctiva), lung abnormalities (bronchitis, pneumonia)
Deficiency of what vitamin is confirmed by an increase in RBC transketolase activity after vitamin supplementation?
Diagnosis of thiamine deficiency can be confirmed by an increase in RBC transketolase activity that occurs after thiamine is supplemented.
What three inflammatory cytokines mediate cachexia?
There is no clear understanding for the exact cause of cachexia in the diseases stated, but there seems to be a connection with inflammatory cytokines, such as tumor necrosis factor-alpha (nicknamed cachexin, TNF-α), interferon gamma (IFN-γ), and interleukin 6, (IL-6), which leads to neuroendocrine signaling for decreased anabolism and increased catabolism.
What is the most common vitamin deficiency in the United States?
Vitamin B9 (folate) is the most common vitamin deficiency in the United States.
What people are at a higher risk for thiamine deficiency?
In the United States, thiamine deficiency is most common in alcoholics (due to poor nutrition and that excess alcohol limits the body’s ability to absorb and store thiamine.)
Acetate is generated in the metabolism of alcohol.
What is this acetate converted to?
Most of the acetate enters the bloodstream, converted to acetyl-CoA by acetyl-CoA synthase in extrahepatic tissues and used to generate cellular energy.
What are some food sources of Vitamin K? What are other sources of Vitamin K?
Vitamin K is obtained from green leafy vegetables (supply K1, phylloquinone) and from bacterial synthesis in the colon (supply K2, menaquinone).
Besides its role as an antioxidant and in collagen synthesis, what are two other functions of vitamin C?
Other roles of Vitamin C:
- Cofactor for dopamine hydroxylase (dopamine → norepinephrine)
- Reduces iron from Fe3+ → Fe2+, facilitating absorption in the duodenum
What are the signs of vitamin B5 deficiency?
Vitamin B5 deficiency is rare. The signs of deficiency include:
Dermatitis
Enteritis
Alopecia
Adrenal insufficiency
How many calories are in 1 gram of fat?
Calories
1 gram of fat yields 9 calories. Fat is the most energy-dense macronutrient.
1 gram of ethanol yields 7 calories.
1 gram of protein or carbohydrate yields 4 calories.
Notes
What are the three serious forms of energy malnutrition?
There are three serious forms of energy malnutrition:kwashiorkor, marasmus and mixed marasmus-kwashiorkor.
A 36-year-old man with longstanding, poorly controlled schizophrenia, is found to have severe osteomalacia. A review of his records reveals that he very rarely leaves his basement and relies on a grocery delivery service to obtain food. He does state that he drinks a pint of milk per day. Which form of vitamin is most likely deficient?
A Ergocalciferol
B Niacin
C Retinoic acid
D Cholecalciferol
E Pantothenic acid
D Cholecalciferol
Answer Explanation
Osteomalacia occurs with vitamin D deficiency. Several forms of vitamin D are required for normal calcium homeostasis: D2 (ergocalciferol), is the form found in food, especially plants. D3 (cholecalciferol), is made by skin from D2 in response to sunlight. Patients with very dark skin (e.g. black children) or with minimal sunlight exposure are at risk for D3 deficiency.
What causes acrodermatitis enteropathica? What are the symptoms?
Acrodermatitis enteropathica is a very rare inherited zinc deficiencycaused by mutations in a gene that encodes a zinc transporter in the small intestine. Symptoms include periorificial (especially mouth and anus) andacral (hand and feet) dermatitis as well as refractory diarrhea. You can remember this disease because Acrodermatitis = acral dermatitis, and enteropathica = pathology of enterocytes of the small intestine.
Which protein in raw egg whites prevents biotin from being absorbed?
Raw egg whites contain avidin, which binds and sequesters biotin within the GI tract. In the presence of avidin, biotin is eliminated with the feces rather than absorbed. Heating egg whites denatures avidin, rendering it unable to bind biotin.
Vitamin K gamma-carboxylates glutamate residues and thereby activates 6 serum proteins involved with clotting — 4 pro-coagulants, and 2 anti-coagulants. Name these 6 vitamin K-dependent factors.
Vitamin K (“Koagulations-Vitamin” in German): gamma-carboxylates glutamate residues and thereby activates:
4 pro-coagulants: clotting factors IX, X, VII, II (prothrombin)
2 anti-coagulants: protein C, protein S
Which vitamin is a precursor for NADH and NADPH? What is a pharmacological use of this vitamin?
Vitamin B3 (niacin) is a precursor for NADH and NADPH. It is used pharmacologically to increase HDL and decrease LDL, typically as alternative or supplemental therapy to other first-line anti-lipid medications.
A patient with untreated pernicious anemia is expected to have poor function of which enzyme?
A Pyruvate kinase
B α-ketoglutarate dehydrogenase
C Acetaldehyde dehydrogenase
D Glycogen phosphorylase
E Methyltetrahydrofolate homocysteine methyltransferase
E Methyltetrahydrofolate homocysteine methyltransferase
Answer Explanation
The anemia of untreated pernicious anemia is the result of vitamin B12 (cobalamin) deficiency. Vitamin B12 is a cofactor for methylmalonyl Coenzyme A mutase and methyltetrahydrofolate-homocysteine methyltransferase; this enzyme transfers a methyl group onto homocysteine, generating methionine.
α-ketoglutarate dehydrogenase converts α-ketoglutarate + NAD + CoA into succinyl CoA; a citric acid cycle reaction.
Glycogen phosphorylase uses vitamin B6 as a cofactor and releases glucose-1-phosphate from a terminal α-1,4-glycosidic bond from glycogen.
Acetaldehyde dehydrogenase plays a key role in metabolizing aldehydes such as acetaldehyde (from EtOH) and formaldehyde (from methanol).
Pyruvate kinase is a glycolytic enzyme and transfers a phosphate group from PEP to ADP.
What is the end result of the MAPK pathway in insulin signaling?
The MAPK pathway regulates the expression of genes that increase cell growth and DNA synthesis.
Vitamin B6 is a cofactor for which two types of reactions? It is also a cofactor for which enzyme?
Vitamin B6 is a cofactor for:
Transamination
Decarboxylation
Glycogen phosphorylase
Vitamin B6 is also a cofactor for other reactions as well.
Thiamine pyrophosphate is a coenzyme for which four important enzymes?
A vitamin B1 (thiamine) derivative, thiamine pyrophosphate (TPP), is an important coenzyme for several reactions. some of which can be remembered with the mnemonic, ATP:
α-ketoglutarate dehydrogenase
Transketolase
Pyruvate dehydrogenase
Vitamin B1 is also a cofactor for branched-chain ketoacid dehydrogenase.
Are B vitamins water soluble? What is the consequence of this?
vitamins are water soluble; therefore, body stores of B vitamins are quickly depleted (except folate and B12 cobalamin, which are stored in the liver).
Each B vitamin is used in a unique type of biochemical reaction. By understanding the biochemical roles of each B vitamin, one can deduce B vitamin cofactors that are necessary based on the name of the enzyme.
Which malnutrition syndromes can lead to cachexia?
Malnutrition syndromes such as Kwashiorkor and Marasmus can also cause cachexia.
What are four important drugs that can cause an absolute or relative folate deficiency?
Numerous drugs or medications can cause an absolute or relative folate deficiency, including the following most important ones:
Ethanol (suspect folate deficiency in any alcoholic with a macrocytic anemia)
Phenytoin
Trimethoprim/sulfonamides
Methotrexate
What occurs during the rehabilitation phase of treatment for severe malnutrition?
During the rehabilitation phase of treatment for severe malnutrition, feedings and vitamin supplementation continue, with the addition of iron. Training of the patient’s caregiver to provide adequate follow-up care also begins during this perio
A 13-year-old girl is prescribed all-trans retinoic acid for acne vulgaris. From which vitamin is this medication derived?
A Thiamine
B Vitamin D
C Vitamin E
D Niacin
E Vitamin A
E Vitamin A
Answer Explanation
Vitamin A derivatives include retinol, retinal, and retinoic acid (includes all-trans retinoic acid).
What type of organism synthesizes vitamin B12?
Vitamin B12 (cobalamin) is synthesized by bacteria. Vitamin B12 cannot be synthesized by plants or animals.
What are the hematologic findings in patients with vitamin K deficiency?
Vitamin K deficiency leads to hemorrhage with:
Prolonged prothrombin time (PT)
Prolonged activated thromboplastin time (aPTT)
Normal bleeding time
Where is insulin produced?
Insulin is produced in pancreatic β cells in the islets of Langerhans.
What enzymes, in addition to alcohol dehydrogenase and acetaldehyde dehydrogenase, are active during high alcohol concentrations? Where are they present?
During acute high level alcohol ingestion, alcohol along with NADPH are oxidized by cytochrome P450 to acetaldehyde and NADP. Cytochrome P450 are present in the smooth endoplasmic reticulum and have a relatively high Km explaining why they are only active during high alcohol concentrations.
Ethanol + NADPH + O2 → Acetaldehyde + NADP + H2O
What is the role of Vitamin E in protecting cell membranes?
Vitamin E: antioxidant and scavenger of free radicals that protects polyunsaturated fats and fatty acids in cell membranes from lipid peroxidation and protects LDL from oxidation.
What effect on ATP-sensitive potassium channels does glucose have and how does this occur?
Inside the cell, glucose is oxidized in glycolysis to ATP, which closes ATP-sensitive potassium channels on the plasma membrane.
What system, which includes the cytochrome P450 superfamily, can metabolize 10-20% of ethanol to acetaldehyde?
The cytochrome P450 superfamily that metabolized alcohol are part of themicrosomal ethanol oxidizing system (or MEOS). It has the ability to metabolize 10-20% of the ethanol to acetaldehyde.
What is the role of ergocalciferol and cholecalciferol in calcium homeostasis?
Vitamin D2 (ergocalciferol, found in plants) and vitamin D3 (cholecalciferol): increases intestinal absorption of calcium and phosphorous and renal absorption of calcium. It also plays a role in PTH-induced osteoclast activation and resorption of bone.
Specifically during alcohol metabolism, what causes TCA cycle inhibition and, ultimately, ketoacidosis?
Oxaloacetate is reduced to malate to regenerate NAD+. Depletion of oxaloacetate inhibits the TCA cycle. Additionally, high NADH inhibits isocitrate dehydrogenase. Acetyl-CoA accumulates as a result of TCA cycle inhibition and is shunted into ketone production leading toketoacidosis.
Reaction: Oxaloacetate + NADH → Malate + NAD+
Which vitamin is used in the synthesis of coenzyme A?
Vitamin B5 (pantothenic acid) is needed to form coenzyme-A (CoA).
What are the signs of riboflavin deficiency?
Riboflavin deficiency causes:
Cheilitis (cracked angles of the mouth)
Glossitis with a magenta-colored tongue
Corneal vascularization
Why should a patient with hemochromatosis avoid excess consumption of Vitamin C?
Excess consumption of Vitamin C can further increase the risk of iron toxicity in patients already predisposed to iron toxicity. Those at risk includes patients that receive frequent transfusions and those with hereditary hemochromatosis.
hat effect does alcohol metabolism have on the metabolism of barbiturates?
Alcohol can divert CYP450 metabolism of certain drugs (e.g., barbiturates) leading to drug toxicities.
Which type of kidney stone is associated with excess consumption of vitamin C?
Excess consumption of Vitamin C can lead to calcium oxalate nephrolithiasis.
What is the most common cause of vitamin D deficiency? What are some other causes of vitamin D deficiency?
Causes of vitamin D deficiency:
Renal failure (most common cause): deficiency of 1-α-hydroxylase
Inadequate exposure to sunlight: decreased synthesis of vitamin D3
Fat malabsorption: cannot reabsorb fat soluble vitamins
Chronic liver disease: unable to carry out first hydroxylation of vitamin D3
Enhanced liver cytochrome P450 system (e.g. alcohol, phenytoin, barbiturates): increased conversion of 25-hydroxycholecalciferol into inactive metabolite
Primary hypoparathyroidism: need PTH to enhance activity of 1-α-hydroxylase
Type 1 vitamin D-dependent rickets: deficiency of 1-α-hydroxylase
Type 2 vitamin D-dependent rickets: deficiency of vitamin D receptors
How is the insulin signal terminated?
Finally, the insulin signal is terminated when the insulin-receptor complex is endocytosed and degraded.
How does glucose enter the pancreatic beta cell?
Glucose enters the pancreatic β cell through the GLUT2 (insulin-independent) transporter by facilitated diffusion.
In chronic alcoholism, how does decreased protein synthesis cause hepatic fatty change?
Chronically, protein synthesis is impaired, preventing assembly and secretion of VLDL, causing triglycerides to accumulate in the liver resulting in hepatic fatty change (hepatocellular steatosis) seen in chronic alcoholics.
What are some good sources of Vitamin A?
Sources of vitamin A:
Liver
Egg yolks
Leafy greens
Carrots
What are the signs of niacin deficiency?
Niacin deficiency leads to glossitis and may lead to pellagra in severe deficiency. Pellagra is a syndrome of the “3 D’s of B3 deficiency,” which are:
- Diarrhea
- Dermatitis (classically in a “necklace” distribution around the neck)
- Dementia
Why is iron not given during the stabilization phase of treatment for severe malnutrition?
Iron is not given during the stabilization phase because of the (negative) effect of free iron on oxidative stress.
What is the pathogenesis of fatty liver in people with kwashiorkor?
The fatty liver in kwashiorkor is due to decreased apolipoprotein synthesis. Because of decreased apolipoprotein synthesis, fats that would be exported from the liver by apolipoproteins are trapped.
Which enzyme produces calcitriol?
Calcidiol is then hydroxylated to the active form, calcitriol (1,25-dihydroxycholecalciferol) in the kidneys by the enzyme 1-α-hydroxylase.
What are the signs of niacin excess?
Niacin can be used to treat hyperlipidemia; side effects in this setting includeacute skin flushing and the potential development of hyperuricemia and hyperglycemia.
What drug inhibits acetaldehyde dehydrogenase (ALDH)? What metabolite accumulates and what symptoms does it cause?
Disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase (ALDH) leading to increased acetaldehyde concentrations and hangover symptoms. Acetaldehyde is responsible for facial flushing and headaches. Disulfiram is used in treatment of chronic alcoholism.
What is the main stimulus for glucagon release?
The main stimulus for glucagon release is hypoglycemia. The exact mechanism of glucagon release is still being elucidated.
What are the products of cleavage of proinsulin?
Proinsulin is transported through the golgi apparatus and into secretory vesicles, where it is cleaved to yield insulin and C-peptide.
Which amino acid is used to synthesize niacin in the body? What B vitamin is a required cofactor?
Niacin may also be endogenously synthesized from tryptophan in a process using vitamin B6. Prolonged and stark vitamin B6 deficiency may lead to niacin deficiency as well.
What is mixed marasmus-kwashiorkor?
Mixed marasmus-kwashiorkor is a kwashiorkor-type picture (edema, anorexia, dermatitis) superimposed on a patient already suffering from marasmus, triggered by an infectious illness.
Which metal commonly serves as a structural ion in transcription factors?
Zinc is found in >100 enzymes and serves as a structural ion in transcription factors (“zinc-finger” motif).
How does marasmus present?
Marasmus presents with:
- “broomstick extremities” due to muscle wasting/breakdown for energy production.
- no visible fat and rarely any edema.
- A useful memory device for marasmus is: Marasmus causes extreme Muscle wasting.
- Patients with marasmus may also present with decreased height and weight for age, thin, dry skin, bradycardia, hypotension, hypothermia, redundant skin folds, and thin, sparse hair.
What is the most important source of vitamin D?
Endogenous vitamin D is produced by photoconversion of 7-dehydrocholesterol to vitamin D3 in sun-exposed skin (most important source).
What reaction causes lactic acidosis in alcohol metabolism?
The reduction of pyruvate to lactate (lactic acid) produces lactic acidosis.
Reaction: Pyruvate + NADH → Lactate + NAD+
What are the signs of vitamin D toxicity?
Vitamin D toxicity leads to:
Hypercalcemia
Renal calcium stones
Nausea and vomiting
Name 2 sequelae that result from methanol poisoning.
Ingestion of methanol results in:
Metabolic acidosis with an increased anion gap
Reaction: methanol → formaldehyde (highly toxic) → formic acid
Blindness due to toxic injury to retinal ganglion cells
What are the signs of zinc deficiency?
Zinc deficiency can cause:
- Impaired immune function
- Delayed healing of wounds (zinc is a cofactor for matrix metalloproteinases)
- Hair loss
- Hypogonadism
- Anosmia (loss of smell)
- Dysgeusia (taste abnormalities)
- Alcoholic cirrhosis
What are signs of cobalamin deficiency?
Cobalamin deficiency leads to macrocytic anemia and neuropathy:
Subacute combined degeneration: demyelination of the dorsal columns leading to loss of pressure/touch/vibratory sense in the extremities. The lateral corticospinal tract can also be affected, causing UMN type lesion with spastic paralysis.
What rare inherited defect in amino acid transport can cause niacin deficiency?
Hartnup disease is an autosomal recessive defect in intestinal and renal transporters for neutral amino acids. This causes tryptophan excretion in urine and leads to pellagra.
What 4 neurotransmitter synthesis reactions does vitamin B6 (pyridoxine) help catalyze?
Pyridoxine is needed to produce many different compounds, and is a cofactor in steps of many different pathways. Pyridoxine is a cofactor for the following 4 neurotransmitter synthesis reactions:
Glutamate → GABA
Tryptophan → Serotonin
DOPA → Dopamine (dopamine can then go on to form norepinephrine and epinephrine)
Histidine → Histamine
In pancreatic β cells, what is the result of ATP-dependent depolarization on intracellular calcium levels?
The depolarization opens voltage-gated [Ca2+] channels, leading to [Ca2+] influx.
What is the stabilization phase of treatment for severe malnutrition?
The stabilization phase of treatment for severe malnutrition includes treatment of hypoglycemia, hypothermia, and dehydration, as well as initiation of feedings. There is also evidence for use of empiric antibiotics in this phase. Vitamin replacement begins as well, with the exception of iron.
Fomepizole is used as an antidote to treat different types of alcohol poisoning. Fomepizole inhibits which enzyme involved in alcohol metabolism?
A Formaldehyde dehydrogenase
B Acetaldehyde and formaldehyde dehydrogenase
C Acetaldehyde dehydrogenase
D Alcohol dehydrogenase
E Alcohol and acetaldehyde dehydrogenase
D Alcohol dehydrogenase
Answer Explanation
Fomepizole is an inhibitor of alcohol dehydrogenase, the first step of alcohol metabolism. This is the enzyme that is involved in the metabolism of all 3 types of alcohol (ethylene glycol, methanol and ethanol).
Formaldehyde dehydrogenase is only involved in the metabolism of methanol; it converts formaldehyde into formic acid. Acetaldehyde dehydrogenase is only involved in the metabolism of ethanol; it converts acetaldehyde to acetic acid.
How does kwashiorkor present?
The typical presentation of kwashiorkor is a child with a swollen belly due to ascites (accumulation of fluid in the peritoneal cavity) and an enlarged, fatty liver. Patients may also have normal or near normal height and weight, anasarca, pitting edema of the lower extremities, dry, atrophic, peeling skin, dry hair that falls out easily, and dilated intestinal loops.
How is the half-life of insulin different from that of C-peptide and how is this clinically useful?
Insulin has a short half-life of about five minutes. Because of its longer half-life, C-peptide is a good indicator of insulin production and secretion.
How is preproinsulin converted into proinsulin?
Proinsulin is formed when the signal peptide is cleaved in the rER.
What is cachexia?
Cachexia is the loss of body weight and muscle mass often seen in patients with cancer, AIDS, multiple sclerosis and other chronic diseases.
