Usmle Step 1: Biochemistry 3

Front 1

Phenylketonuria

Back 1

- phenylalanine hydroxylase deficiency
- phenylalanine hydroxylase conversts phenylalanine to tyrosine
- tyrosine becomes essential AA and phenylalanine builds up

- symptoms: mental retardation, growth retardation, musty body odor
- treatment: decrease phenylalanine and increase tyrosine in diet

Front 2

Alkaptonuria

Back 2

- homogentisic acid oxidase deficiency
- homogentisic acid oxidase degrades tyrosine
- results in black urin, dark connective tissue and joint pain

Front 3

Albinism

Back 3

- deficiency in tyrosinase (makes melanin from tyrosine) or deficiency in tyrosine transporters (decreased amount of tyrosine and thus melanin)
- increased risk of skin cancer

Front 4

Homocystinuria

Back 4

- caused by either cystathione synthase deficiency, decreased affinity of cystathione synthase for pyridoxal phosphate, or homocystein methyltransferase deficiency

- results in excess homocysteine and cysteine becomes essential
- causes mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation and atherosclerosis

Front 5

Cystinuria

Back 5

- common inherited defect of renal tubular amino acid transporter for cystein, ornithine, lysine and arginine in the PCT of the kidneys
- excess cystine in urine can lied to precipitation as cystine kidney stones (cystine is made of 2 cysteines connected by a disulfide bond)

Front 6

Maple syrup urine disease

Back 6

- blocked degradation of branched AAs (Ile, Val, Leu) due to decreased alpha-ketoacid dehydrogenase
- causes increased alpha-ketoacids in the blood, especially Leu
- causes severe CNS defects, mental retardation and death

- urine smells like maple syrup
- I Love Vermont maple syrup

Front 7

Purine salvage deficiencies

Back 7

- adenosine deaminase deficiency
- can cause SCID
- excess ATP and dATP imbalances nucleotide pool via feeback inhibition of ribonucleotide reductase (preventing DNA synthesis and thusly decreased lymphocyte count)

- Lesh-Nyhan syndrome
- HGPRT deficiency (converts hypoxanthine to IMP and guanine to GMP) causing excess uric acid production (because purines cannot be salvaged)
- symptoms: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
- HGPRT: He's Got Purine Recovery Trouble

Front 8

Fasting and starvation

Back 8

- Days 1-3
1. hepatic glycogenolyis and glucose release
2. adipose release of FFA
3. muscle and liver shifting fuel use from glucose to FFAs
4. hepatic gluconeogenesis

- After Day 3
muscle protein loss is maintained by hepatic formation of ketone bodies, supplying the brain and heart

- After several weeks
ketone bodies become main source of energy for brain, so less muscle protein is degraded than during days 1-3. after fat stores are depleted, vital protein degradation accelerates, leading to organ failure and death

Front 9

Insulin

Back 9

- made in beta cells of pancreas in response to ATP from glucose metabolism acting on K+ channels and depolarizing cells (required for adipose and skeletal muscle uptake of glucose)
- GLUT2 receptors are found in beta cells and GLUT4 in muscle/fat (GLUT1 in brain/RBCs)
- insulin inhibits glucagon release by alpha cells of pancreas
- serum C-peptide is not present with exogenous insulin intake (proinsulin --> insulin + C-peptide)

Front 10

Glycogen

Back 10

- branches have alpha-1,6 and linkages have alpha-1,4 bonds

Front 11

Glycogen storage diseases

Back 11

- Von Gierke's disease: glucose-6-phosphatase deficiency resulting in fasting hypoglycemia, increased glycogen in liver, increased blood lactate and hypatomegaly

- Pompe's disease: lysosomal alpha-1,4-glucosidase dificiency causing cardiomegaly and systemic findings leading to early death

- Cori's disease: debranching enzyme alpha-1,6-glucosidase deficiency causing a milder form of type 1 (VGD)with normal blood lactate levels

- McArdle's disease: skeletal muscle glycogen phosphorylase deficiency causing increased glycogen in muscle, but cannot break it down, leading to muscle cramps, myoglobinuria with strenous excersize

- Very Poor Carbohydrate Metabolism

Front 12

Gaucher's disease

Back 12

- lysosomal storage disease: beta-glucocerebrosidase deficiency (glucocerebroside builds up)
- symptoms: hepatosplenomegaly, aseptic necrosis of femur, bone crisis, Gaucher's cells (macrophages that look like crumpled tissue paper)

Front 13

Tay-Sachs disease

Back 13

- lysosomal storage disease: hexosaminidase A deficiency (GM2 ganglioside builds up)
- symptoms: progressive neurodegeneration, developmental delay, cherry red spot (on retina), lysosomes with onion skin

Front 14

Fatty acid metabolism cites

Back 14

- citrate shuttle: transports acetyl-CoA from the mitochondrial matrix to the cytoplasm for fatty acid synthesis
- carnitine shuttle: transports acyl-CoA (fatty acid + CoA) into mitochondrial matrix for breakdown (carnitine deficiency leads to an inability to utilize LCFAs and toxic accumulation)

Front 15

Cholesterol synthesis

Back 15

- HMG-CoA reductase: rate limiting enzyme, inhibitory target of statins

Front 16

Essential fatty acids

Back 16

- linoleic and linolenic acids (arachidonic acid, if linoleic acid is absent)
- eicosanoids are dependent of essential fatty acids

Front 17

Lipoproteins (enzymes)

Back 17

- Pancreatic lipase––degradation of dietary TG in small intestine.
- Lipoprotein lipase (LPL)––degradation of TG circulating in chylomicrons and VLDLs.
- Hepatic TG lipase (HL)––degradation of TG remaining in IDL.
- Hormone-sensitive lipase––degradation of TG stored in adipocytes.
- Lecithin-cholesterol acyltransferase (LCAT)––catalyzes esterification of cholesterol.
- Cholesterol ester transfer protein (CETP)––mediates transfer of cholesterol esters to other lipoprotein particles.

Front 18

Major apolipoproteins

Back 18

- A-I: activates LCAT
- B-100: Binds to LDL receptor, mediates VLDL secretion
- C-II: cofactor for lipoprotein lipase
- B-48: mediates chylomicron secretion
- E: mediates extra (remnant) uptake

Front 19

LDL vs HDL

Back 19

- LDL transports cholesterol from liver to tissue
- HDL transports cholesterol
from periphery to liver
- HDL is Healthy, LDL is Lousy

Front 20

Chylomicrons

Back 20

- secreted by intestinal epithelial cells
- deliver dietary triglycerids to peripheral tissues
- deliver cholesterol to liver in form of chylomicron remnants

Front 21

Lipoproteins

Back 21

- VLDL: delivers hepatic triglycerides to peripheral tissues
- IDL: delivers triglycerides and cholesterol to liver, where they are degraded to LDL (IDL is formed in the degeneration of VLDL)
- LDL: delivers hepatic cholesterol to peripheral tissues
- HDL: mediates centripetal transport of cholesterol (from periphery to liver)

Front 22

Familial dyslipidemias

Back 22

- Type I-hyperchylomicronemia: lipoprotein lipase deficiency or altered apolipoprotein C-II causes increased blood levels of chylomicrons (and thusly TG, cholesterol)

- Type IIa-hypercholesterolemia: ↓ LDL receptors cause increased LDL (and thusly cholesterol) in blood

- Type IV-hypertriglyceridemia: hepatic overproduction of VLDL causes increased circulating VLDL (and thusly TGs)

Front 23

Porphyrias

Back 23

- lead poisoning, acute intermittent porphyria, porphyria cutanea tarda

- symptoms: the 5 P's - Painful abdomen, Pink urine, Polyneuropathy, Psychological distrubances, Precipitated by drugs

Front 24

Heme catabolism

Back 24

- Heme → biliverdin → bilirubin
- bilirubin is removed from blood by liver, conjugated with glucuronate and excreted in bile

Front 25

Hemoglobin

(composition, regulation, types)

Back 25

- composed of 4 polypeptide subunits (2 α and 2 β)
- T (taut) form has low affinity for O2
- R (relaxed) form has high affinity for O2

- regulation: ↑ Cl−, H+, CO2, 2,3-BPG, and temperature favor T form over R form (shifts dissociation curve to your right, leading to ↑ O2 unloading).
- fetal hemoglobin (2α and 2γ) has lower affinity for 2,3-BPG than adult hemaglobin and thus has higher affinity for O2 (allowing it to "steal" O2 from maternal circulation)

Front 26

CO2 transport in blood

Back 26

- transported as bicarbonate
- transported by hemoglobin; binds to hemoglobin (not at O2 site)

Front 27

Hemoglobin modifications

Back 27

- Methemoglobin: oxidized form of hemoglobin (Fe3+ instead of Fe2+), treated with methylene blue

- carboxyhemoglobin: form of hemoglobin bound to CO in place of O2 (CO has 200x greater affinity than O2 for hemoglobin)