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Flashcards in Metabolism Deck (86)
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1
Q

Mitochondria

A

Fatty acid oxidation, acetyl CoA production, TCA cycle, oxidative phosphorylation

2
Q

Cytoplasm

A

Glycolysis, fatty acid synthesis, HMP (ribose) shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis

3
Q

Mitochondria and Cytoplasm metabolism

A

Heme synthesis, urea cycle, gluconeogenesis (HUG takes two)

4
Q

Kinase

A

Uses ATP to add high energy phosphate group onto substrate, ex phosphofructokinase

5
Q

Phosphorylase

A

Add inorganic phosphate group onto substrate without energy, ex glycogen phosphorylase

6
Q

Phosphatase

A

Removes phosphate group from substrate, ex fructose-1.6-biphosphatase

7
Q

Dehydrogenase

A

Catalyzes oxidation-reduction reactions, ex pyruvate dehydrogenase

8
Q

Carboxylase

A

Transfers CO2 group with the help of biotin, ex pyruvate carboxylase

9
Q

Hydroxylase

A

Adds -OH gruop onto substrate, ex tyrosin hydroxylase

10
Q

Mutase

A

Relocates a functional group within a molecule

11
Q

Glycolysis

A

RLE: phosphofructokinase

Up: AMP, fructose-2,6-biphosphate

Down: ATP, citrate

12
Q

Gluconeogenesis

A

RLE: fructose-1,6-biphosphatase

Up: ATP, acetyl CoA

Down: AMP, fructose-2,6-biphospate

13
Q

TCA cycle

A

RLE: isocitrate dehydrogenase

Up: ADP

Down: ATP, NADH

14
Q

Glycogenesis

A

RLE: glycogen synthase

Up: glucose-6-phosphate, insulin, cortisol

Down: epinephrine, glucagon

15
Q

Glycogenlysis

A

RLE: glycogen phosphrylase

Up: epinephrine, glucagon, AMP

Down: G6P, insulin, ATP

16
Q

HMP (pentose) shunt

A

RLE: Glucose-6-phosphate-dehydrogenase

Up: NADP

Down: NADPH

17
Q

Urea cycle

A

RLE: carbamoyl phosphate synthetase I

Up: n-acetylglutamate

18
Q

Fatty acid synthesis

A

RLE: acytel CoA carboxylase

Up: insulin, citrate

Down: glucagon, palmitoyl-CoA

19
Q

Fatty acid oxidation

A

RLE: carnitine acyltransferase I

Up: malonyl-CoA I

20
Q

Ketogenesis

A

RLE: HMG-CoA synthase

21
Q

Cholesterol synthesis

A

RLE: HMG CoA reductase

Up: insule, thyroxine

Down: glucagon, cholesterol

22
Q

ATP production

A

Anaerobic glycolysis produces 2 net ATP

Aerobic metabolism of glucose produces 32 net APT (30 via TCA and ETC and 2 from anaerobic glycolysis)

23
Q

NAD (nicotinamides)/FAD

A

Used in catabolic processes to carry reducing equivalents away as NADH/FADH

24
Q

NADP/NADPH

A

Used in HMP shunt for anabolic process (steroid and fatty acid synthesis as supply of reducing equivalents), respiratory burst (immune defense), cytochrome 450 system (reducing agent), and glutathion reductase

25
Q

Hexokinase

A

Phosphorylate glucose to G6P for glycolysis

Located in most tissues but not liver or beta cells in pancreas

NOT induced by insulin

Feedback inhibited by G6P concentration

Gene mutation NOT associated with diabetes

At low glucose concentration, sequester glucose in tissue

26
Q

Glucokinase

A

Phosphorylate glucose to G6P

Located in liver and beta cells of pancreas

Induced by insulin

NOT feedback inhibited by G6P

Gene mutation associated with diabetes

At high glucose concentration, glucose stored in liver

27
Q

F2,6BP regulation

A

FBPase 2 and PFK-2 are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A

Fasting state:
Increased glucagon –> increased cAMP –> increased protein kinase A –> increased FBPase 2 and decreased PFK-2, less glycolysis and more gluconeogenesis

Fed state:
Increased insulin –> decreased cAMP –> decreased protein kinase –> decreased FBPase 2 and increased PFK-2, more glycolysis and less gluconeogenesis

28
Q

Pyruvate dehydrogenase complex

A

Mitochondrial enzyme complex linking glycolysis and TCA cycle, differentially regulated in fed/fasting state (active in fed state)

Reaction: pyruvate (from glycolysis) + NAD + CoA –> acetyl-CoA + CO2 + NADH

The complex contains 3 enzymes that requires 5 cofactors: pryophosphate, FAD, NAD, CoA, lipoic acid

Deficiency: build up of pyruvate that gets shunted to lactate and alanine leading to neurologic defects, lactic acidosis. Treatment w/ increased intake of keogenic nutrients

29
Q

Pyruvate metabolism

A
  1. Alanine aminotransferase (ALT) via B6: converts pyrvate to alanine, alanine carries amino groups to the liver from muscle for urea cycle
  2. Pyruvate carboxylase via B7 biotin: converts pyruvate to oxaloacetate (in mitochondria), which can replenish TCA cycle or be used for gluconeogensis
  3. Pyruvate dehydrogenase via B1, B2, B3, B5, lipoic acid: converts pyruvate to acetyl-CoA for TCA cycle
  4. Lactic acid dehydrogenase via B3: end of anaerobic glycolysis (major pathway in RBC, leukocytes, lens, cornea, testes)
30
Q

TCA cycle Detail

A

Conversion of pyruvate to acetyl-CoA produces 1 NADH

TCA produces 3 NADH, 1 FADH2, 1 GTP per acetyl-CoA, which converts to 10 ATP (NADH = 2.5 ATP, FADH2 = 1.5 ATP)

Citrate Is Kreb’s Starting Substrate For Making Oxaloacetate

31
Q

Electron transport inhibitors

A

Directly inhibit electron transport, causing a decrease in proton gradient and block of ATP synthesis

Ex: Rotenone (insecticide), cyanide, antimycin A (produced by Streptomyces, carbon monoxide

32
Q

ATP synthase inhibitors

A

Directly inhibit mitochondrial ATP synthase

Ex: oligomycin (produced by Streptomyces)

33
Q

Uncoupling agents

A

Increase permeability of membrane, causing a decrease in proton gradient and increased O2 consumption. ATP synthesis stops but electron transport continues.

Produces heat

Ex: 2-4 dinitrophenol (weight loss), aspirin

34
Q

HMP shunt pentose phosphate pathway reactions

A

Provides a source of NADPH from ABUNDANTLY available G6P

NADPH is required fro reductive reactions such as glutathion reduction inside RBC to reduce oxidative stress and fatty acid and cholesterol synthesis

Also used for ribose synthesis

Oxidative reaction: G6P –> ribulose-5-Pi + 2 NADPH + CO2 with G6PD as RLE

Nonoxidate reaction: ribulosse-5-Pi –> ribose-5-Pi + G3P + F6P with phosphopentose iosmerase transketolases, needing B1 (thiamine)

35
Q

Respiratory burst (oxidative burst)

A

Involves activation of phagocyte NADPH oxidase complex (in neutrophils, monocytes), which utilizes O2 as a substrate to release reactive oxygen species as immune response

36
Q

G6PD deficiency

A

X-linked recessive disorder, more prevalent among blacks

Decreased NADPH in RBC leads to hemolytic anemia

Heinz bodies: oxidized hemoglobin precipitated within RBC

Bite cells: result from phagocytic removal of Heinz bodies by splenic macrophages

37
Q

Essential fructosuria

A

Defect in fructokinase, autosomal recessive

Benign with fructose appears in blood and urine

38
Q

Fructose intolerance

A

Autosomal recessive

Hereditary deficiency of aldolase B, leading to accumulation of fructose-1-P, a decrease in available phosphate, and inhibition of glycogenolysis and gluconeogenesis

Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting

Treatment: decrease intake of both fructose and sucrose

39
Q

Galactokinase deficiency

A

Autosomal recessive

Galactitol accumulates, leading to galatose in blood and urine and infantile cataracts

40
Q

Galactosemia

A

Autosomal recessive

Absence of galactose-1-phosphate uridyltransferase, leading to damage caused by accumulation of galacitol, failure to thrive, jaundice, hepatomegaly, infantile cataracts, and intellectual disability

Treatment: exclude galactose and lactose from diet

41
Q

Lactase deficiency

A

Primary: age-dependent decline after childhood

Secondary: loss of brush border due to gastroenteritis, autoimmune disease

Congenital: rare

Symptoms: bloating, cramps, flatulence, osmotic diarrhea

Treatment: avoid dairy, choose lactose-free milk

42
Q

Essential amino acids

A

Methionine, valine, histidine, isoluecine, phenylalanine, threonine, tryptophan, leucine, lysine

Any Help In Learning These Little Molecules Proves Truly Valuable

43
Q

Urea cycle Detail

A

Amino acid catabolism results in the formation of metabolites (pyruvates, acetyl CoA) together with excess NH3

NH3 in liver is converted in liver mitochondria to carbamoyl phosphate via carbamoyl phosphate synthetase I (N-acetylgutamate as cofactor) and evntually to urea via urea cycle and excreted by kidney

Ordinarily (orithine) Careless (carbamoyl phosphate) Crappers (citruline) Are Also Frivolous About Urination

44
Q

Hyperammonemia

A

Can be acquired (eg liver disease) or hereditary (urea cycle enzyme deficiencies)

Results in excess NH4+, which depletes alpha-keotglutarate and leads to inhibition of TCA cyle

Signs: tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Treatment: limit protein diet, lactulose to acidify the GI tract and trap NH4+ for GI excretion

45
Q

N-acetylglutamate deficiency

A

Hyperammonemia

Presentation is identical to carbamoyl phosphate synthetase I deficiency

Increased orithine concentration with NORMAL urea cycle enzymes suggest N-acetylglutamate deficiency

46
Q

Orthinie transcarbamylase deficiency

A

X-linked recessive

Enzyme converts carbamoyl phosphate and ornithine to citrulline as part of urea cycle

Findings: increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia

47
Q

Phenylketonuria

A

Autosomal recessive

Due to decreased phenyalanine hydroxylase. Tyrosine becomes essential AA

Findings: increased phenalaine, intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor

Treatment: decreased phenylalanine and increased tyrosine in diet

48
Q

Alkaptonuria

A

Autosomal recessive, benign

Congential deficiency of homogentisate oxidase in the degradative pathway of tyrosine

Findings: dark connective tissue, brown pigmented sclerae, debilitating arthralgias (toxicity to cartilage)

49
Q

Homocystinuria

A

Autosomal recessive

Methionine cystathionine –> cysteine

Findings: increased homocysteine in urine, intellectual disability, osteoporosis, thrombosis, atherosclerosis

Treatment: depending on which enzyme is deficient

50
Q

Cystinuria

A

Autosomal recessive 1:7000

Hereditary defect of renal proximal tubule and intestinal AA transporter for Cysteine

Excessive cysteine in the urine can lead to precipitation of hexagonal cystine stones

Treatment: urinary alkalinization and good hydration

51
Q

Maple syrup urine disease

A

Autosomal recessive

Blocked degradation of branched amino acids (isoleucine, leucine, valine) due to decreased alpha ketoacid dehydrogenase

Findings: urine smells like maple syrup, CNS defects, death

Treatment: restriction of branched AA, thiamine supplement

52
Q

Skeletal muscle glycogen

A

Glycogenolysis –> G1P –> G6P, which is rapidly metabolized during exercise

53
Q

Hepatocytes glycogen

A

Stored and undergoes glycogenolysis to maintain blood sugars at appropriate levels

Glycogen branches have alpha 1-6 bonds while linkages have alpha 1-4 bonds

54
Q

Von Gierke disease

A

Glycogen storage disease, Autosomal recessive

Glucose 6 phosphatse deficiency

Severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly

Treatment: frequent oral glucose

55
Q

Pompe disease

A

Glycogen storage disease, autosomal recessive

Lysomal alpha 1-4 glucosidase deficiency

Cardiomyopathy

Pompe trashes the Pump

56
Q

Cori disease

A

Glycogen storage disease, autosomal recessive

Debranching enzyme deficiency

Milder form of Von Gierke

57
Q

McArdle disease

A

Glycogen storage disease, autosomal recessive

Skeletal muscle glycogen phosphorylase deficiency

Increased glycogen in muscle that cannot be broken down, leading to painful muslce cramps and myoglobinuria with strenuous exercise. Arrhythmia w/ electrolyte abnormalities

McArdle Muscle

58
Q

Fabry disease

A

Lysosomal storage disease, XR

Alpha galactosidase A deficiency

Peripheral neuropahty, cardivascular/renal disease

59
Q

Gacher disease

A

Lysosomal storage disease, AR

Glucocerobrosidase deficiency

Hepatosplenomegaly, pancytopenia, aspectic necrosis of bone, Gaucher cells (lipid laden macrophages resembling crumbling tissue paper)

60
Q

Niemann-Pick disease

A

Lysosomal storage disease, AR

Sphingomyelinase deficiency

Progress neurodegeneration, hepatosplenomegaly, cherry red spots on macula, foam cells (lipid laden macrophages)

61
Q

Tay-Sachs disease

A

Lysosomal storage disease, AR

Hexosaminidase A deficiency

Progressive neurodegeneration, developmentally delayed, cherry red spots on macula, NO hepatomegaly

62
Q

Krabbe diseaes

A

Lysosomal storage disease, AR

Galactocerobrosidase deficiency

Peripheral neuropathy, developmental delays, optic atrophy

63
Q

Metachromatic leukodystrophy

A

Lysosomal storage disease, AR

Arysulfatase A deficiency

Central and peripheral demyelination with ataxia and demntia

64
Q

Hurler syndrome

A

Lysosomal storage disease, AR

Alpha-L-iduronidase deficiency

Developmental delays, airway obstruction, corneal clouding

65
Q

Hunter syndrome

A

Lysosomal storage disease, AR

Iduronate sulfatase deficiency

Mild Hurler + aggressive behaviors, no corneal clouding

66
Q

Carnitine deficiency

A

Inability to transport LCFAs into mitochondria for degradation, resulting in toxic accumulation

Causing weakkness, hypotonia, and hypoketotic hypoglycemia

67
Q

Metabolic fuel use: fed state (after meal)

A

Glycolysis and aerobic respiration

Insulin stimulates storage of lipids, proteins, and glycogen

68
Q

Metabolic fuel use: fasting (between meals)

A

Hepatic glycogenlysis (major), hepatic gluconeogensis, adipose release of FFA (minor)

Glucagon, adrenaline stimulate use of the reserve fuel

69
Q

Metabolic fuel use: starvation 1-3 days

A

Blood glucose level maintained by hepatic glycogenolysis, adipose release of FFA, muscle and liver usage of FFA instead of glucose, hepatic gluconeogenesis from peripheral tissue lactate and alanine and glycerol from adipose tissue

Glycogen reserves depleted after day 1, glucose reserved for RBCs since RBCs lack mitochondria and cannot use FFA/ketones

70
Q

Metabolic fuel state: starvation after day 3

A

Adipose stores (ketone becomes main source of energy)

Vitals proteins degradation accelerates w/ depletion of adipose storage

Excess storage determines survival time

71
Q

Cholesterol synthesis detail

A

Rate limiting step is catalyzed by HMG-CoA reductase, which converts HMG-CoA to mevalonate

2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT) for VLDL, LDL, HDL transport

Stains competitively and reversibly inhibit HMG-CoA reductase

72
Q

Pancreatic lipase

A

Degradation of dietary triglycerides in small intestine

73
Q

Lipoprotein lipase

A

Degradation of TG circulating in chylomicrons and VLDLs Found on vascular endothelial surfaces

74
Q

Hepatic TG lipase

A

Degradation of TG remaining in IDL

75
Q

Hormone sensitive lipase

A

Degradation of TG stored in adipocytes

76
Q

Lectinin-cholesterol acyltransferase (LCAT)

A

Catalyzes esterificatino of cholesterol

77
Q

Cholesterol ester transfer protein (CETP)

A

Mediates transfer of cholesterol esters to other lipoprotein particles (VLDL, LDL, IDL)

78
Q

Apoplipoprotein

A

E: mediates remnant uptake

A1: activates LCAT

C2: lipoprotein lipase cofactor

B48: mediates chylomicron secretion

B100: binds LDL receptor

79
Q

Low density lipoprotein

A

Transports cholesterol from liver to tissues

Formed by hepatic lipase modification of IDL in the peripheral tissue

Taken up by target cells via receptor mediated endocytosis

80
Q

High density lipoprotein

A

Transports cholesterol from peripheral to liver

Secreted from both liver and intestine

81
Q

VLDL

A

Delivers hepatic TG to peripheral tissue, secreted by liver

82
Q

IDL

A

Formed in degradation of VLDL

Delivers TGs and cholesterol to liver

83
Q

Chylomicron

A

Delivers dietary TGs to peripheral tissue

Delivers cholesterol to liver in the form of chylomicron remnant, which are mostly depleted of their TGs

Secreted by intestinal epithelial cells

84
Q

Familial dyslipidemia type 1: hyperchylomicronemia

A

AR, lipoprotein lipase deficiency

Increased chylomicrons and cholesterol

Causes pancreatitis, hepatosplenomegaly, pruritic xanthomas

85
Q

Familial dyslipidemia type 2a: familial hypercholesterolemia

A

AD, absent or defective LDL receptors

Increased LDL and cholesterol

Causes accelerated atherosclerosis, tendon xanthomas, (achilles), corneal arcus

86
Q

Familial dyslipdemia type 4: hypertriglyceridemia

A

AD, hepatic overproduction of VLDL

Increased VLDL, TG

Causes pancreatitis