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CMB > CMB Exam 2 - All > Flashcards

CMB Exam 2 - All Flashcards

1
Q

Lewis acid

A

e- acceptor (ie any ion/molecule that can accept a pair of nonbonding valence electrons). eg CO2

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2
Q

Why/how is there such a big discrepancy between H+ and HCO3- levels?

A

We need the excess HCO3- buffer for pH and to accomodate the continuous production of organic acids. Discrepancy established by kidney actively excreting H+ and actively reabsorbing HCO3-.

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3
Q

How does the body monitor blood pH?

A

Chemoreceptors in the carotid are sensitive to pO2, pCO2 and/or pH

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4
Q

respiratory acidosis

A

Caused by compromised ventilation, over-production or increased intake of CO2.

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5
Q

metabolic acidosis

A

Usually caused by influx of (exogenous) organic acid.

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6
Q

respiratory compensation

A

In the case of acidosis, resp. rate increases to breathe off more CO2. In the case of alkalosis, resp. rate decreases.

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7
Q

anion gap

A

~12 ± 4 mEq/L = the quantity of anions in the serum (mostly HCO3- and Cl-) not balanced by cations (mostly Na+). Plasma is electro-neutral, so the “gap” of is actually balanced by negatively charged proteins. Exogenous acid increases the gap.

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8
Q

metabolic acidosis

A

Acidosis from introduction of exogenous acid (HCO3- drops too).

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9
Q

ELMPARK

A

Ethylene glycol (glycolate; Ca++, oxalate crystals); Lactic acidosis (lactic acid); Methanol (paraldehyde); Aspirin (salicylate and lactate); Renal tubular acidosis (sulfate & phosphate; NORMAL anion gap acidosis), uremia (inability to excrete NH4+; end-stage renal disease); Ketoacidosis (β-OH butyrate, acetoacetate).

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10
Q

hyperkalemia

A

Excess K+ in the blood. Can result from acute acidosis or from quick correction of chronic alkalosis.

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11
Q

respiratory alkalosis

A

Hyperventilation, breathe off too much CO2. Resulant hypokalemia can depolarize neurons.

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12
Q

metabolic alkalosis

A

Increase in blood HCO3- (eg vomit out your acid, exogenous bicarb/antacids, respiratory compensation (hypoventilation increases both H+ and HCO3-). Resulant hypokalemia can depolarize neurons.

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13
Q

hypokalemia

A

Low K+ in the plasma. Can result from acute alkalosis (H+ leaves the cell driving K+ in.

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14
Q

What is normal arterial [HCO3-]?

A

~24 mEq/L HCO3-

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15
Q

What is normal arterial pCO2?

A

~35-45 mmHg CO2

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16
Q

What anion becomes elevated when ethylene glycol (antifreeze) is ingested?

A

Glycolate (Ca++, oxalate crystals)

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17
Q

What anion becomes elevated in lactic acidosis? (hypoxemia, ischemia)

A

Lactic acid

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18
Q

What anion becomes elevated when methanol is ingested?

A

Formic acid

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19
Q

What anion becomes elevated when paraldehyde is ingested?

A

Acetaldehyde, acetate

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20
Q

What anion becomes elevated when excess aspirin is ingested? (complicated)

A

Salicylate and lactate

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21
Q

What anion becomes elevated in renal tubular acidosis (NORMAL anion gap acidosis)?

A

Sulfate, phosphate

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22
Q

What anion becomes elevated in ketoacidosis?

A

β-OH butyrate, acetoacetate

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23
Q

Why is fructose more “evil” than glucose?

A

In the liver, since it can’t enter PP pathway or glycogen synthesis it’s preferentially converted to F1P to FA to TG to VLDL, bypassing glucokinase and PFK-1 (which are important regulators). This can also lead to deficiencies in aldolase B, causeing accumulation of F1P. Can rapidly deplete liver ATP/Pi levels and increase uric acid production (gout, hypertension).

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24
Q

normal fasting glucose levels

A

80-140 mg/dL (centered around 110 mg/dL)

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25
Q

Which enzymes are activated by glucagon? What are the results of this change?

A

Activation of: PKA, F-2,6 bisphoshatase, phosphorylase kinase, glycoden phosphorylase, hormone-sensitive lipase. This results in activation of gluconeogenesis and glycogenolysis.

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26
Q

Which enzymes’ activity is inhibited by glucagon? What are the results of the changes?

A

Inhibition of: PFK-2, PFK-1 indirectly, pyruvate kinase, glycogen synthase. Results in inhibition of glycolysis and glycogen synthesis.

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27
Q

How does insulin reverse the action og glucagon?

A

Via phosphodiesterase-mediated breakdown of cAMP (PKA inactivation) and unregulated enzyme dephosphorylation by protein phosphatases. Also, acitvation of: PFK2 (and PFK1 indirectly, by synthesis of F-2,6BP), pyruvate kinase, and glycogen synthase. Inactivation of: F-2,6 bisphosphatase, phosphorylase kinase, glycogen phosphorylase, and hormone-sensitive lipase.

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28
Q

What are the major gluconeogenic substrates?

A

Lactate, glycerol, and amino acids (except leu and lys). NEVER acetyl-CoA fatty acids.

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29
Q

“limit dextrin”

A

Glycogen with the 4-residue branch

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30
Q

acid maltase

A

Degrades glycogen in the lysosomes.

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31
Q

What are the three main categories of glycogen storage diseases?

A

Hepatic, myopathic, or “miscellaneous”.

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32
Q

type 1a glycogenosis

A

(von Gierke disease; glucose-6-phosphatase deficiency) Hepatic-hypoglycemic glycogen storage disease. SSx: chubby cheeks, hypoglycemia, lactic acidosis/ketosis, hepatomegaly, hypotonia, slow growth, bleeding, diarrhea, gout, hypertriglyceridemia, xanthomas. If untreated with dietary therapy, can result in early death from hypoglycemia, or hepatomas in later childhood.

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33
Q

type 1b glycogenosis

A

(Glucose-6-phosphate translocase deficiency) Similar presentation as type Ia (hepatomegaly, hypoglycemia, lactic acidosis, ketosis, bleeding, gout, hypertriglyceridemia, xanthomas) but with neutropenia and GI dysfunction. Risk of hepatomas or death from hypoglycemia, plus risk of infection.

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34
Q

type II glycogenosis

A

(Pompe disease; lysosomal α-glucosidase deficiency) Myopathic. Presents with cardiomegaly, symmetrical muscle weakness, heart failure, and a shortened P-R interval. Prognosis is usually death in first year; enzyme therapy is available but expensive.

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35
Q

type III glycogenosis

A

(Forbes disease; debranching enzyme deficiency) Affects both muscles and liver. Presents with hepatomegaly (that resolves with age), hypoglycemia, ketonuria, and may show muscle fatigue. Ok prognosis.

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36
Q

type IV glycogenosis

A

(Andersen disease; branching enzyme deficiency) Presents with hepatic cirrhosis and early liver failure, but doesn’t directly affect blood glucose levels. Prognosis is usually death within the first year.

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37
Q

type V glycogenosis

A

(McArdle disease; muscle phosphorylase deficiency) Presents with muscle fatigue beginning in adolescence (similar to type VII, Tarui disease). Good prognosis with sedentary lifestyle.

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38
Q

type VI glycogenosis

A

(Hers disease; liver phosphorylase deficiency) Hepatic-hypoglycemic glycogen storage disease, ketonuria. Probably good prognosis.

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39
Q

type VII glycogenosis

A

(Tarui disease; muscle phosphofructokinase deficiency) Muscle fatigue beginning in adolescence. Good prognosis with sedentary lifestyle.

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40
Q

type VIII glycogenosis

A

(Phosphorylase kinasae deficiency) Hepatic-hypoglycemic glycogen storage disease.

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41
Q

von Gierke disease

A

Type 1a glycogenosis; glucose-6-phosphatase deficiency. Hepatic-hypoglycemic glycogen storage disease. SSx: chuccy cheeks, hypoglycemia, lactic acidosis/ketosis, hepatomegaly, hypotonia, slow growth, bleeding, diarrhea, gout, hypertriglyceridemia, xanthomas. If untreated with dietary therapy, can result in early death from hypoglycemia, or hepatomas in later childhood.

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42
Q

Pompe disease

A

Type II glycogenosis; lysosomal α-glucosidase. Myopathic. Presents with cardiomegaly, symmetrical muscle weakness, heart failure, and a shortened P-R interval. Prognosis is usually death in first year, but gene therapy looks promising.

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43
Q

Forbes disease

A

Type III glycogenosis; debranching enzyme deficiency. Affects both muscles and liver. Presents with hepatomegaly (that resolves with age), hypoglycemia, ketonuria, and may show muscle fatigue. Ok prognosis.

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44
Q

Andersen disease

A

Type IV glycogenosis; branching enzyme deficiency. Presents with hepatic cirrhosis and early liver failure, but doesn’t directly affect blood glucose levels. Prognosis is usually death within the first year.

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45
Q

McArdle disease

A

Type V glycogenosis; muscle phosphorylase deficiency. Presents with muscle fatigue beginning in adolescence (similar to type VII, Tarui disease). Good prognosis with sedentary lifestyle.

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46
Q

Hers disease

A

Type VI glycogenosis; liver phosphorylase deficiency. Hepatic-hypoglycemic glycogen storage disease, ketonuria. Probably good prognosis.

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47
Q

Tarui disease

A

Type VII glycogenosis; muscle phosphofructokinase deficiency. Muscle fatigue beginning in adolescence. Good prognosis with sedentary lifestyle.

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48
Q

Which of the glycogenoses is predominantly hepatic-hypoglycemic?

A

Types I (Ia - von Gierke disease - and Ib), VI (Hers disease), and VIII. Type III (Forbes disease) does muscle AND liver. These patients tend to present with hepatomagaly and hypoglycemia.

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49
Q

Which of the glycogenoses is predominantly myopathic?

A

Types V (McArdle disease) and VII. Type III does muscle AND liver. This tend to manifest with muscle cramps after exercise and a lack of lactase (due to blocked glycolysis).

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50
Q

Which of the glycogenoses affect miscellaneous tissues? What do their deficient enzymes have in common?

A

Types II (Pompe disease) and IV (Andersen disease). They lead to glycogen build-up in many organs, but cardiomegaly is the most prominent feature.

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51
Q

“gallop” heart rhythm

A

Consistent with heart failure. Can present with many conditions including Pompe disease.

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52
Q

What qualifies as elevated glucose levels?

A

> 126 mg/dL fasting, >200mg/dL post-prandial (especially on 2 occasions, 2 hours after 75g dose of glucose (OGTT)

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53
Q

Mutations in which genes cause neonatal diabetes mellitus?

A

KCNJ11 and ABCC8 (subunits of the ATP-sensitive potassium channel) and others.

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54
Q

What mutations are associated with MODY?

A

Glucokinase. Mutations shift the Km higher.

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55
Q

LADA

A

(latent autoimmune diabetes in adults) slow autoimmune destruction of

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56
Q

What are the 3 components of “ketone bodies”?

A

Acetone, acetoacetate, and hydroxybutyrate. Only acetone is a ketone, the other two are acids.

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57
Q

gestational diabetes

A

Human placental lactogen has anti-insulin action and reduces insulin sensitivity. Develops in ~7% of pregnancies.

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58
Q

What are the major complications of diabetes?

A

Infections, retinopathy, neuropathy, nephropathy, heart disease % stroke, impotence, and ketoacidosis (Type I)

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59
Q

What are the complications of diabetic ketoacidosis?

A

Hyperglycemia, vomiting, dehydration, kussmaul breathing, confusion, coma (~600 mg/dL, extremem dehydration). Treatment is insulin and rehydration + electrolytes.

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60
Q

How can insulin resistance directly increase blood glucose?

A

Lower insulin sensitivity causes lipolysis and increases fatty acid oxidation, which will decrease glucose utilization in the muscle and increase gluconeogenesis in the liver.

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61
Q

adiponectin

A

Activates AMPK, which appears to enhance insulin sensitivity; is anti-inflammatory; improves clearance of FFA, glucose and TG; suppresses gluconeogenesis

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62
Q

AMPK

A

Activated says LIVER: Increases glycolysis and decreases gluconeogenesis in the liver; MUSCLE: increasing FFA uptake, β-oxidation, and glucose uptake in the muscle.

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63
Q

What happens to glucagon levels as DM-2 progresses?

A

Glucagon response decreases as DM-2 progresses (meaning that instead of responding, it stays high).

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64
Q

Why can’t glucometers be used in diagnostics for glucose disregulation?

A

Glucometers have high variability at high glucose levels, so they are NEVER used for diagnosis

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65
Q

When can a random blood glucose test be diagnostic for diabetes?

A

When it’s over 200mg/dL AND the patient shows Si/Sx.

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66
Q

HbA1C

A

Diagnostic for diabetes when >6.5%

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67
Q

“Abnormal Newborn State Screen”

A

Screens are for anticipatory education and early intervention. We screen for:

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68
Q

Munchausen syndrome by proxy

A

Munchausen is the psychological need to have/invent symptoms. “By proxy” refers to a parent’s need to do so for a child.

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69
Q

PKU: presentation/progression

A

Affected infants are normal at birth but soon develop rising plasma phenylalanine, impairing brain deveopment. Severe mental retardation is evident by 6 months. Other SSx include seizures, hypopigmentation (since tyrosine is a precursor of melanin), and eczema, musty or mousy-smelling urine (from shunting biproducts).

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70
Q

maternal PKU

A

75%-90% of children born to adult PKU females with hyperphenylalaninemia are mentally retarded and microcephalic, 15% have congenital heart disease. Caused by excess prenatal phenylalanine.

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71
Q

PKU: prevalence, inheritance

A

1:10,000 births; autosomal recessive; common in people of Scandanavian descent (tend to be blond), uncommon in Jewish and black populations

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72
Q

PKU: enzyme deficiency

A

Phenylalanine hydroxylase; 2% of cases are BH4 abnormalities, which CANNOT be treated by restriction of phenylalanine.

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73
Q

PKU: screening and diagnosis

A

Only blood levels of phenylalanine can differentiate benign hyperphenylalaninemia (>360uM) from malignant PKU (>600uM). 5x the normal level of phenylaline = malignant. WThen we can screen to identify PAH mutations (there are at least 500, but only some are malignant).

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74
Q

PKU: treatment

A

Immediate, strict restriction of phenylalanine. Restriction within 10 days of birth can allow normal cognitive function. Tyrosine becomes essential.

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75
Q

phenylalanine hydroxylase

A

Converts phenylalanine into tyrosine. Deficiency = Phenylketonuria; hyperphenyalaninemia.

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76
Q

tetrahydrobiopterin

A

Cofactor for phenylalanine hydroxylase. Deficiency leads to a malignant form of PKU that can’t be treated by restriction of dietary phenylalanine.

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77
Q

Which metabolic disorder is autosomal dominant?

A

Familial hypercholersterolemia

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78
Q

Which metabolic disorder is x-linked?

A

Ornithine Carbamoyl Transferase deficiency

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79
Q

urine acylglycine profile

A

Excessive intermediates of fatty acid oxidation and organic acid catabolism are conjugated with glycine, so the urine acylglycine profile reflects this accumulation.

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80
Q

plasma acylcarnitine profile

A

Excessive intermediates of fatty acid oxidation and organic acid catabolism are conjugated with carnitine, so the plasma acylcarnitine profile reflects this accumulation.

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81
Q

An increase in guanidinoacetic acid reflects a disorder of…

A

creatine biosynthesis.

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82
Q

What is the treatment for “transient tyrosinemia of the newborn”?

A

Ascorbic acid.

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83
Q

Tyrosinemia Type I: enzyme deficiency

A

Due to fumarylacetoacetate hydrolase deficiency (causes liver disease)

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84
Q

Tyrosinemia Type I: SSx

A

Accumulated liver metabolites, bleeding disorder, hypoglycemia, hypoalbuminemia, elevated transaminases, and defects in renal tubular function. May cause hepatocellular carcinoma.

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85
Q

Tyrosinemia Type I: screening and diagnosis

A

After an abnormal neonatal screen, check quantitative plasma tyrosine and blood/urine succinylacetone. Diagnosis is confirmed by increased concentration of succinylacetone. Some DNA testing is available as well.

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86
Q

Tyrosinemia Type I: treatment

A

Nitisinone (an inhibitor of the oxidation of liver metabolites?) and restricted dietary phenylaline and tyrosine.

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87
Q

nitisinone

A

Indicated for tyrosinemia type I; inhibits oxidation of toxic accumulation of liver metabolites.

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88
Q

Tyrosinemias Type II and III

A

More benign than type I, because blockage happens earlier in the pathway and succinylacetone is not produced. May result in keratitis (severe visual disturbances) and hyperkeratosis of palms and soles. Treatment with a restricted phenylalanine/tyrosine diet is effective.

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89
Q

hyperkeratosis

A

Abnormal thickening of the skin. Can result from tyrosinemia types II and III.

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90
Q

keratitis

A

Results in sever visual disturbance. Can result from tyrosinemia types II and III.

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91
Q

Homocystinuria: inheritance, prevalence

A

Autosomal recessive; 1:200,000 live births

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92
Q

Homocystinuria: enzyme defect

A

Deficiency of cystathionine β-synthase (normally converts homocysteine to cysteine); causes buildup of homocysteine, which is reconverted to methionine.

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93
Q

Homocystinuria: SSx

A

Elevated blood/urine homocysteine and blood methionine. Produces a clinical syndrome that includes dislocated ocular lenses; long, slender extremities; malar flushing; livedo reticularis; skeletal features; mental retardation and/or psychiatric illness. Major thromboses are a risk.

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94
Q

Homocystinuria: diagnosis

A

Elevated total homocysteine in the blood. Hypermethioninemia. Some genetic testing is available.

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95
Q

Homocystinuria: treatment

A

Homocysteine restricted diet with cystine and folate supplementation (since folate is trapped in the process of remethylation of homocysteine to methionine). Some forms respond to pyridoxine therapy, and the others need betaine to help with methylation.

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96
Q

MSUD: inheritance, incidence

A

(branched chain ketoaciduria) Autosomal recessive; 1:250,000 live births

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97
Q

MSUD: enzyme deficiency

A

(branched chain ketoaciduria) A deficiency of the decarboxylase initiates the degradation of the ketoacid analogs of the three branched chain amino acids—leucine, isoleucine, and valine.

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98
Q

MSUD: SSx

A

(branched chain ketoaciduria) Within 1-4 weeks: poor feeding, vomiting, tachypnea, CNS depression and EXTENSOR SPASMS, opisthotonos, seizures. Urine has odor of maple syrup. Lab manifestations: hypoglycemia, metabolic acidosis (ketone bodies and branched-chain acids) with elevation of undetermined anions.

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99
Q

MSUD: diagnosis

A

(branched chain ketoaciduria) Large increases in plasma leucine, isoleucine, and valine concentrations and identification of alloisoleucine in the plasma in excess.

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100
Q

MSUD: treatment

A

(branched chain ketoaciduria) Provision of adequate calories with restriction of leucine; hemodialysis/hemofiltration/peritoneal dialysis if in acidotic crisis; monitor for cerebral edema. Liver transplantation effectively treats MSUD.

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101
Q

OTC deficiency: inheritance

A

X-linked.

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102
Q

OTC deficiency: SSx

A

High neonatal mortality in males. In females, SSx can include hyperammonemia, recurrent emesis, lethargy, seizures, developmental delay, and episodic confusion. They may spontaneously limit protein intake.

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103
Q

OTC deficiency: diagnosis

A

Plasma AA profile may show low citrulline and arginine, with high glutamate and alanine. Urine organic acid profile after protein loading shows orotic acid. DNA testing is also available.

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104
Q

OTC deficiency: treatemt

A

Treatment for hyperammonemia; hemodialysis; liver transplantation (especially in males).

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105
Q

ASL deficiency: diagnosis

A

Elevated citrulline in screen, elevated argininosuccinate in the urine.

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106
Q

hyperammonemia: treatment

A

Reduced protein intake; IV glucose (to slow catabolism); alternate pathway agents (eg sodium benzoate, sodium phenylacetate); arginine supplementation. In some cases, liver transplantation may be necessary.

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107
Q

Cystinuria: treatment

A

Penicillamine and other compounds increase the solubility of cystine by complexing with it.

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108
Q

Hartnup syndrome

A

Impaired transport of tryptophan; results in pellagra-like symptoms (dermatitis, diarrhea, dementia). Treatment with tryptophan is successful.

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109
Q

isomers

A

Two molecules with the same chemical formula but different arrangement of bonds/atoms.

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110
Q

epimers

A

Two molecules that are identical but differ at one stereocenter.

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111
Q

enantiomers

A

Two epimers that are mirror (non-superimposable) images of each other, aka “optic isomers” because they bend light differently. The D moieties are biologically relevant.

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112
Q

What is the difference between L and D carbohydrates? Which is biologically relevant?

A

They’re enantiomers (optical isomers).

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113
Q

Describe how D-glucose forms a cyclic molecule.

A

Nucleophilic attack from the OH- on C5 to C1 (ketone). C4 could do it too but the smaller ring is less stable.

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114
Q

anomers

A

Cyclical sugar molecules that are identical but differ at the anomeric carbon (C1) in the orientation of the groups.

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115
Q

What is the difference between α- and β-sugars?

A

They’re anomers; α has the axial group, β has the equitorial group.

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116
Q

What is the half life of hemoglobin?

A

6 weeks

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117
Q

pyranoses

A

6 member ring common to sugars; loosely resembles a pyran molecule

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118
Q

furanose

A

5 member ring common to sugars; loosely resembles a furan molecule

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119
Q

Maillard reaction

A

Refers to the glycation/fructation of free amino groups of proteins like hemoglobin; leads to production of AGEs.

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120
Q

Why is sucrose more stable than lactose?

A

In sucrose the reducing end of the carbons is tied up in the O-glycosidic bond, making it less reactive. Lactose has a reducing end free, so it’s susceptible to oxidation.

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121
Q

amylose

A

Long, unbranched D-glucose (α1,4) starch.

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122
Q

amylopectin

A

Highly branched D-glucose (α 1,4 & 1,6) starch.

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123
Q

glycogen

A

Very highly branched form of D-glucose. Starch.

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124
Q

dextrans

A

Branched starch from bacteria & yeast; componet of dental plaques.

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125
Q

cellulose

A

Unbranched starch with β1,4 bonds, making it impossible for our amylases to break them down.

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126
Q

glycosaminoglycans

A

Group of heteropolysaccharides that are important components of the extracellular matrix (eg collagens, elastins, fibronectin). All have STRUCTURAL importance.

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127
Q

hyaluronan

A

Glycosaminoglycan; forms viscous solutions for lubricants in synovial fluid of joints and vitreous humor of the eye; component of cartilage and tendons; LONGEST glycosaminoglycan

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128
Q

chondroitin sulfate

A

Glycosaminoglycan; covalently bound part of proteoglycans; contributes to tensile strength of connective tissue (eg wall of aorta)

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129
Q

keratan sulfate

A

Glycosaminoglycan; present in cornea, cartilage, bone, and dead cell stuff (hair, horns, hofs, nails, claws, etc.)

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130
Q

heparan sulfate

A

Glycosaminoglycan; produced by all animal cells; high degree of sulfation allows it to interact with many proteins (eg growth factors, enxymes, etc.)

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131
Q

proteoglycans

A

Major component of ECM. Glycosaminoglycans bound to membrane or secreted protein. Often longer, unbranched carb chains.

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132
Q

glycoproteins

A

Have 2 major functions: can be receptors (sugars give specificity) or enzymes (sugars protect from the environment). Sugars can also serve as a signal for breakdown. Often shorter, branched carb chains.

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133
Q

glycosphingolipids

A

Specialized lipids modified by oligosaccharides. Abundant in brain and stuff.

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134
Q

homopolysaccharides

A

Branching or non-branching chains of like monosaccharides with NUTRITIONAL function.

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135
Q

heteropolysaccharides

A

Branching or non-branching chains of various monosaccharides with STRUCTURAL function.

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136
Q

What major metabolic pathways occur in the cytosol?

A

Glycolysis, portions of gluconeogenesis, glycogen metabolism, pentose phosphate pathway

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137
Q

What major metabolic pathways occur in the mitochondria?

A

TCA, e- transport chain, most ATP synthesis, fatty acid oxidation.

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138
Q

Where is most of the cell’s NAD+/NADH located?

A

~90% in mitochondria

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139
Q

Where is most of the cell’s NADP+/NADPH located?

A

Mostly in the cytosol (to maintain a reductive environment).

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140
Q

In a healthy cell, what is the ratio of NAD+ to NADH? Why?

A

NAD+&raquo_space; NADH. If NADH accumulates it probably means that ATP production is low.

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141
Q

In a healthy cell, what is the ratio of NADP+ to NADPH? Why?

A

NADP+/NADPH = 0.05. The major role of NADP is to maintain a reductive environment in the cytosol to protect proteins etc.

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142
Q

α-amylase: what is it, where is it?

A

An endoglycosidase specific for α-1,4 bonds. Present in saliva but mostly in the duodenum.

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143
Q

What are the monosaccharide components of sucrose?

A

Glucose and fructose.

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144
Q

What are the monosaccharide components of lactose?

A

Glucose and galactose.

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145
Q

Other than the site of action, what is the big difference between endoclycosidases and exoglycosidases?

A

Endoglycosidases are secreted (and thus need to be replaced) whereas exoglycosidases are anchored into the villi.

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146
Q

GLUT4 - what is it and where is it?

A

The only insulin-dependent glucose transporter (UNIPORT); present in adipocytes, cardiac and skeletal muscle.

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147
Q

GLUT2 - what is it and where is it?

A

NOT insulin dependent; allows glucose, fructose and galactose to follow the gradient. “Senses” blood glucose levels (high KM for glucose). Present in the pancreas and liver, as well as most enterocytes.

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148
Q

GLUT5

A

Fructose uniport into enterocytes, cells of proximal tubules.

149
Q

SGLT1

A

Sodium glucose symporter. Needs Na+ gradient.

150
Q

GLUT1

A

Ubiquitous glucose and galactose transporter (gradient).

151
Q

GLUT3

A

Glucose and galactose uniport into brain, placenta, testes.

152
Q

What tissues are insulin dependent? Which are insulin independent?

A

DEPENDENT: Muscle, fat (liver too, but not for energy). INDEPENDENT: brain, RBCs

153
Q

glycolysis - what’s the purpose? net result?

A

LIVER: does glycolysis to turn free glucose into triglycerides (in the fed state), exporting them as VLDL. ADIPOCYTES: use glycolysis for glycerol-3-P synthesis (in the fed state). OTHER TISSUES: use glycolysis for energy; RGC & brain always; muscle un demand (regardless of fed/fast state.

154
Q

Outline the steps of glycolysis, including names of enzymes (and intermediates if that helps).

A

[image]

155
Q

Where in the cell does glycolysis take place?

A

In the cytosol.

156
Q

hexokinase (what does it do, and in which tissues is it present)

A

Phosporylates hexoses (including glucose) nonspecifically and unidirectionally. Requires ATP hydrolysis. Present in RBCs, muscle, and fat (and most tissues other than the liver and pancreas). Inhibited by glucose-6-phosphate (product inhibition). Expression NOT regulated by insulin.

157
Q

glucokinase (what does it do, and in which tissues is it present)

A

Unidirectionally phosphorylates glucose (ATP hydrolysis!), forming glucose-6-phosphate (removing it from glc pool). In the pancreas, it “measures” rate of glucose intake to regulate insulin release. Most common in LIVER and PANCREAS. Secuestered to nucleus by GKRP in the presence of F6P (fasted state), released from GKRP in the presence of F6P (fed state).

158
Q

phosphohexose isomerase

A

Converts glucose-6-phosphate to fructose-6-phosphate (and vice versa).

159
Q

PFK-1

A

(phosphofructokinase-1) Phosphorylates (ATP hydrolysis!) fructose-6-phosphate to fructose-1,6-bisphosphate. Inhibited by ATP always. LIVER: Activated by F-2,6-BP (product of PFK-2). MUSCLE/RBCs: activated by AMP.

160
Q

aldolase

A

Splits fructose-1,6-bisphosphate into 2 molecules: glyceraldehyde-3-phosphate and dihydroacetone phosphate.

161
Q

triosephosphate isomerase

A

Converts dihydroxyacetone phosphate (the other product of fructose-1,6 catabolism) to glyceraldehyde-3-phosphate. (Side note: in adipose tissue, this generates NAD+?)

162
Q

glyceraldehyde-3-phosphate dehydrogenase

A

Oxidizes glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, generating NADH.

163
Q

What do dehydrogenases do?

A

In general, they oxidize a molecule (strip a hydride) and reduce a carrier like NAD+ to NADH.

164
Q

phosphoglycerate kinase

A

Dephosphorylates 1,3-phosphoglycerate, generating 3-phosphoglycerate and ATP.

165
Q

phosphoglycerate mutase

A

Moves the phosphate on 3-phosphoglycerate to the 2- position.

166
Q

enolase

A

Pulls a water molecule out of 2-phosphoglycerate forming phosphoenolpyruvate.

167
Q

pyruvate kinase

A

Dephosphorylates phosphoenolpyruvate, forming pyruvate and ATP. Regulates glycolysis (hormones). Activated by F16BP, in the liver it can be activated via dephosphorylation. Inhibited by ATP or in the liver by phosphorylation by PKA.

168
Q

What is the limiting factor of glycolysis? How is this factor replenished?

A

NAD+ supply is limited for glyceralehyde-3-phosphate dehydrogenase. It must be replenished: in anaerobic conditions by conversion of lactate to pyruvate by lactate dehydrogenase, or in aerobic conditions by a glycerol-3PDH shuttle that passes H2 to the mitochondria.

169
Q

lactate dehydrogenase

A

In anaerobic conditions, converts pyruvate to lactate to regenarate NAD+.

170
Q

glycerol-3 phosphate shuttle

A

In aerobic conditions, regenerates NAD+ by passing the hydrogens onto dihydroacetone phosphate (DHAP) forming glycerol-3-phosphate, and then onto flavoproteins in the inner mitochondrial membrane.

171
Q

malate-aspartate shuttle

A

The hydrogens from G3P are transfered to NAD+. NAD+ is regenerated by passing the hydrogens on to oxaloacetate forming malate, which enters the mitochondria and participates in the TCA cycle. Aerobic conditions in the cardiac muscle, liver and kidney.

172
Q

2,3-bisphosphoglycerate in RBCs

A

A small portion of 1,3-bisphosphoglycerate is transfered to 2,3-BPG instead of 3-phosphoglycerate; this way the cell misses out on an ATP molecule, but the 2,3-BPG is important to regulate O2 affinity of Hb.

173
Q

What’s different between the binding curves of glucokinase vs hexokinase?

A

Hexokinase reaches Vmax almost immediately (hyperbolic curve). The glucokinase curve is sigmoidal and has a Km 100x higher. As the concentration of gllucose increases, so does the velocity. This is how the pancreas keeps insulin release proportional glucose concentration.

174
Q

What happens to an individual if their glucokinase has a higher Km?

A

Glucokinase’s velocity would decrease, decreasing the pancreas’ release of insulin and elevating normal fasting blood glucose levels.

175
Q

GKRP

A

(Glucokinase regulatory protein) sequesters glucokinase to the nucleus in the presence of F6P (ie fasted state); dissociates in the presence of F1P (fed state).

176
Q

PFK-2

A

(phosphofructokinase-2) A small proportion of F6P is phosphorylated by PFK-2 to form F-2,6-BP, which is absolutely necessary for PFK-1 to become active. PFK-2 is inhibited (via phosphorylation) as a consequence of glucagon action, which also inhibits PFK-1 and activates phosphorylase. Also activated by AMP in RBCs/muscle/brain.

177
Q

F-2,6-BP

A

Product of phosphorylation of F6P by PFK-2. Absolutely necessary for PFK-1 activation in the LIVER.

178
Q

What modulates glycolysis in liver vs muscle/RBCs?

A

LIVER: PK activates in presence of insulin, glucagon action phosphorylates PFK-2 preventing its product F-2,6-BP from activation PFK-1 (thus inhibiting glycolysis). MUSCLE/RBCs: ATP/(AMP+ADP) ratio; ATP binds to and inhibits PFK-1 and PK, AMP activates PFK-2.

179
Q

“Metabolic Syndrome”

A

Characterized by central obesity (“apple shape”). Fructose increases risk of this.

180
Q

essential fructosuria

A

Benign condition resulting from a deficiency of fructokinase. Characterized by hyperfructosemia and fructosuria.

181
Q

hereditary fructose intolerance

A

Severe autosomal recessive defect in aldolase B. Treatment is immediate removal of fructose from the diet.

182
Q

classic galactosemia

A

Due to loss of uridylyltransferase (GALT). Typically presents in the first weeks after birth; presents with poor feeding, weight loss, vomiting, diarrhea, lethragy; hepatomagaly, jaundice, and bleeding disorders; renal tubule disease; can lead to blindness. SSx resolve upon galactose restriction.

183
Q

galactosemia

A

Due to loss of galactokinase (GALK). Can result in cataracts and/or blindness. SSx resolve upon galactose restriction.

184
Q

epimerase deficiency

A

(GALE) 1 of 3 kinds of galactose intolerance. Has 2 forms: the benign one is in erythrocytes, the severe looks like GALT deficiency (ie GI issues, liver issues, kidney issues, potential blindness).

185
Q

How does glycogen synthesis occur?

A

Glucose –(glucokinase)–> Glu6P –(phosphoglucomutase)–> Glu1P —-> UDP-glucose + glycogenin - UDP –(glycogen synthase)–> elongated glycogen –(branching enzyme)–> branched/elongated glycogen

186
Q

glycogenin

A

Glycogen synthesis primer: self-glucosylating homodimer, each attaches glu from UDP-glu to a tyrosine residue on the other monomer and they get pushed apart as they grow.

187
Q

How does glycogen degradation occur?

A

Under the influence of glucagon, glycogen phosphorylase uses a phosphate (instead of water) to split glucose off glycogen, leaving Glu1P. WHEN THERE ARE 4 LEFT IN A BRANCH (ie “limit dextrin”): transferase moves 3 over to the straight chain, an α-1,6-glucosidase removes the last molecule of glu. The free Glu1P is changed to Glu6P by phosphoglucomutase and then to glucose by Glu-6-phosphatase (expressed ONLY in the liver).

188
Q

Outline the mechanism by which glucagon/epinephrine cause glycogen degredation.

A

Both glucagon and epinephrin activate adenylyl cyclase, which turns ATP to cAMP. cAMP causes the dissociation of the regulatory subunits of PKA from it’s catalytic subunits. PKA activates phosphrylase kinase, which activates phosphorylase. Phosphorylase uses a phosphate to separate Glu1P from the glycogen chain. PKA also inactivates glycogen synthase to avoid cycling.

189
Q

phosphoglucomutase

A

Turns Glu1P (from glycogenolysis) to Glu6P for glycolysis

190
Q

glucose-6-phosphatase

A

IN THE LIVER, dephosphorylates Glu6P so glucose can be released into the blood.

191
Q

Which reactions in glycolysis are irreversible? In each case, how does gluconeogenesis overcome this?

A

Glucokinase, PFK-1, and pyruvate kinase reactions are all highly exergonic.

192
Q

Where in the cell does gluconeogenesis occur?

A

Mostly in the cytosol (some precursors are generated in the mitochondria)

193
Q

Name the 4 kinds of gluconeogenic substrates.

A

Lactate (produced by RBCs and muscle from pyruvate), amino acids (except leucine and lysine), glycerol, and all of the TCA intermediates (which does not include acetyl-CoA).

194
Q

What role does fat (fatty acids) have in gluconeogenesis?

A

Glucagon signals release of FFAs from adipose tissue (by hormone-sensitive lipase), which is broken down in the liver and provides ATP for gluconeogenesis.

195
Q

The Cori Cycle

A

The recycling by the liver of the lactate produced in RBCs; lactate becomes the pronciple substrate for gluconeogenesis.

196
Q

Walk through all the steps of gluconeogenesis, starting with lactate.

A

Lactate + NAD+ –(lactate dehydrogenase)–> pyruvate + NADH –(enters mitochondria)–> pyruvate –(pyruvate carboxylase, biotin)–> OAA –(transamination)–> Asp –(leaves mitochondria)–> Asp –(deamination)–> OAA –(phosphoenol-pyruvate carboxylase)–> PEP –(enolase)–> 2-phosphoglycerate –(phosphoglycerate transmutase)–> 3-phosphoglycerate –(phosphoglycerate kinase)–> 1,3-bisphosphoglycerate + NADH –(glyceraldehyde-3-phosphate dehydrogenase)–> glyceraldehyde-3-phosphate + NAD+ –(aldolase)–> fructose-1,6-bisphosphate –(fructose-1,6-bisphosphatase in the absence of F-2,6-P)–> fructose-6-phosphate –(phosphohexose isomerase)–> glucose-6-phosphate –(enters ER)–> glucose-6-phosphate –(glucose-6-phosphatase)–> GLUCOSE! :D take it to the blood!

197
Q

Describe the process of phosphoenol pyruvate formation in the absence of lactate.

A

First we need to generate pyruvate (since liver doesn’t do glycolysis in fed state); in the absence of lactate, amino acids like alanine (but not leucine or lysine) are turned into pyruvate. Pyruvate enters mitochondria and is carboxylated to oxaloacetate (pyruvate carboxylase, biotin dependent). OAA is reduced to malate, leaves the mitochondria and is re-oxidized to OAA. OAA is then decarboxylated (phosphoenol-pyruvate carboxylase, GTP) to form PEP.

198
Q

phosphohexomutase

A

Turns Glu6P to Fru6P and vice versa.

199
Q

fructose-1,6-bisphosphatase

A

Dephosphorylates F-1,6-P to F6P in gluconeogenesis.

200
Q

What are the effects of ethanol in gluconeogenesis?

A

The metabolism of ethanol uses up all the NAD+ in the cytosol, inhibiting gluconeogenesis (lactate dehydrogenase and malate dehydrogenase both need NAD+). This is especially for pre-teens and young adults who can’t process it as well.

201
Q

What family of metabolic enzymes requires biotin (Vit B7)?

A

Carboxylases.

202
Q

What are the potential causes of biotin deficiency?

A

Defective enzymes (either that attach it to the carboxylases or the biotinidase that detaches it), mal absorption (eg too much avidin in diet), excessive drinking, smoking, or antibiotic treatment.

203
Q

Outline the oxidative pentose phosphate pathway.

A

Glucose-6-phosphate + NADP+ –(glucose-6-phosphate dehydrogenase)–> NADPH+ a lactone structure that is acted on by another enzyme and NADP+ —-> NADPH + CO2 + ribulose-5-phosphate (NOT RIBOSE-5-phosphate). So, a six carbon sugar has been oxidized to 2 NADPH and a 5 carbon sugar.

204
Q

What is the purpose of the pentose phosphate pathway?

A

To provide 2 things: NADPH (for reductive biosynthetic pathways, maintaining the cytosolic reductive environment via glutathione) and/or ribose-5-phosphate (for nucleotide synthesis). If only NADPH is needed then the ribose-5-P is recycled to G-6-P to repeat PPP.

205
Q

xylulose-5-P

A

An important activator of protein phosphatases in the liver, speeding the reversal of glucagon activity.

206
Q

superoxide in RBCs

A

Produced spontaneously in RBCs: ~1% of O2 oxidizes Hb-Fe2+ to Hb-3+, and the O2- can combine with water to form H2O2. These ROS denature hemoglobin (Heinz bodies) and damage cell membranes, leading to cell lysis and hemolytic anemia.

207
Q

Heinz bodies

A

Denatured hemoglobin precipitates, resulting from ROS in blood cells.

208
Q

hemolytic anemia

A

RBC lysis from Heinz bodies and cell membrane damage as a result of ROS.

209
Q

glutathione

A

Tripeptide (synthesized by enzyme, NOT RIBOSOMES!) with a central cysteine residue that can be oxidized to form a homodimer. Monomers are substrate for glutathione peroxidase and are used to reduce oxidized Hb (ie Hb with disulfide bonds). The monomers are regenerated by glutathione reductase, which uses NADPH to reduce the glutathione dimer back to monomers.

210
Q

glutathione peroxidase

A

Uses to molecules of glutathione to repair oxidative damage (eg Heinz bodies), leaving a glutathione dimer.

211
Q

glutathione reductase

A

Regenerates glutathione monomers by reducing the homodimer that forms after glutathione peroxidase uses them to repair oxidative damage.

212
Q

Explain how macrophages generate bacteriocidal ROS.

A

MAcrophages take the NADPH from the PPP: NADPH + O2 –(NADPH oxidase)–> O2- + NADP+ –(superoxide dismutase)–> H2O2, which can be dumped on bacteria or –(myeloperoxidase)–> HOCl.

213
Q

G6PDH deficiency

A

X-linked recessive. RBC most affected (lots of oxidative stress). Common in areas with endemic malaria.

214
Q

chronic granulomatous disease

A

Deficiency in G6PDH (

215
Q

favism

A

Hemolytic anemia; can be induced by a variety of oxidative agents (infection, drugs, fava beans); all victims are G6PDH deficient. SSx: anemia, elevated bilirubin,dark urine.

216
Q

kernicterus

A

Neonatal G6PDH deficiency elevates bilirubin, which can accumulate in grey matter. Treatment includes bili-lights.

217
Q

Outline the conversion of pyruvate to acetyl-CoA.

A

1) E1*TPP displaces CO2 from pyruvate and donates an H+. 2) The hydroxyethyl group is transfered to oxidized (S-S) lipoyllisine on E2, reducing the lipoyllysine and converting the hydroxyethyl to an acetyl group. 3) E2 then attaches CoA-SH to the acyl lipoyllysine forming acetyl-CoA, which leaves. 4) Lipoyllysine is still reduced, so E3 uses FAD to oxidize it. 5) NAD+ then oxidizes the FADH2.

218
Q

List the cofactors necessary for the pyruvate dehydrogenase complex.

A

TPP (vit B1), lipoic acids, FAD (riboflavin, vit B2), NAD+ (niacin, vit B3), CoA (pantothenic acid, vit B5).

219
Q

E1 subunit of PDH

A

This is the actual pyruvate dehydrogenase component. Comprises 20-30 subunits.

220
Q

E2 subunit of PDH

A

This is the dihydrolipoyl transacetylase component. Comprises 60 subunits.

221
Q

E3 subunit of PDH

A

This is the dihydrolipoyl dehydrogenase component. Comprises 6 subunits.

222
Q

Beriberi: SSx

A

Thiamin deficiency. SSx include diarrhea and liver disease. Early stage symptoms sinclude fatigue, irritability, poor memory, sleep distrubances, chest pain, anorexia, abdominal pain, constipation. Common in alcoholics and in non-varied diets like white rice.

223
Q

Beriberi: biochemistry

A

Thiamin deficiency inhibits pyruvate dehydrogenase. Accumulation of pyruvate, lactate, citrate, and α-ketoglutarate. Reduces actylcholine synthesis (acetyl-CoA is a precursor).

224
Q

Describe the regulation of PDH

A

ACTIVATED: allosterically via AMP, CoA and NAD+, Ca++ (ie low ATP + nececssary substrates) and covalently via dephosphorylation. INHIBITION: allosterically via ATP, acetyl-CoA, and NADH, and covalently via autophosphorylation of E1.

225
Q

Outline the “important” steps of TCA (according to Dory’s slides).

A

You add acetyl-CoA (2 carbons) to OAA and make citrate. [In the liver, citrate leaves for the cytoplasm and is reconverted to acetyl-CoA]. The other important things to remember are that the first CO2 comes off via isocitrate dehydrogenase (yielding 1 NADH), the next comes of via α-ketoglutarate dehydrogenase (analogous to PDH; yields 1 NADH), then there’s substrate-level phosphorylation producing GTP and succinate. Succinate dehyrogenase (a member of the e-transport chain) uses FAD to oxidize succinate, then fumarate is converted to malate which is oxidized by malate dehydrogenase (yields 1 NADH) to OAA. So: we add 2 carbons to the cycle and we get 3 NADH, 1 FADH2, and some substrate-level phosphorylation.

226
Q

What is the major role of the TCA cycle?

A

In most cells: produce NADH from acetyl-CoA. In the liver: use excess energy for biosynthesis of fatty acids (TCA rarely goes past citrate in the liver).

227
Q

What are the overall net products and reactants of the TCA cycle?

A

Acetyl CoA + 3 NAD + FAD + GDP + Pi —-> HS-CoA + 2 CO2 + 3 NADH + FADH2 + GTP

228
Q

What would happen the the level of acetyl-CoA in the liver if all the OAA is busy (gluconeogenesis)?

A

Acetyl-CoA would accumulate in the liver if there’s not enough OAA because it needs OAA to run in the TCA cycle. The liver will have to turn acetyl-CoA into ketone bodies.

229
Q

What is the importance of citrate in the liver?

A

In the liver, the TCA cycle stops after acetyl-CoA is added to OAA forming citrate. Citrate is then exported from the mitochondria to the cytoplasm to be reconverted to acetyl-CoA. Ultimately important for fatty acid biosynthesis.

230
Q

pyruvate carboxylase

A

In the fed state, can convert a portion of pyruvate to oxaloacetate to avoid the accumulation of acetyl-CoA.

231
Q

PEP carboxykinase

A

Converts PEP to OAA (esp in heart and skeletal muscle) to prime TCA.

232
Q

How does alcohol inhibit gluconeogenesis?

A

Cyctosolic alcohol dehydrogenase turns all the NAD to NADH, which always drives pyruvate to lactate, inhibiting gluconeogenesis. (alcohol also enters the mitochondria and turns into acetaldehyde and the acetate in a process that uses up mitochondrial NAD as well).

233
Q

Pasteur effect

A

Refers to the fact that glycolysis decreases in tht presence of O2 because TCA and electron transport chain produce energy omre efficiently.

234
Q

ubiquinone (coenzyme Q)

A

e- acceptor in the e- transport chain. Contains a hydrophobic isoprene side chain whose synthesis happens to be inhibited by statins.

235
Q

cytochromes

A

Red or brown heme proteins with iron (Fe3+) or copper one-electron carriers. All (EXCEPT CYTOCHROME C!) are integral membrane proteins. Cytochrome C is water soluble. A and B hemes are held in a cage, whereas C hemes are covalently bound to C cytochromes.

236
Q

Outline the general steps of the e- transport system.

A

NADH dehydrogenase in Complex I oxidizes NADH to NAD+, simultaneously pumping an H+ across the membrane. Complex I (from NADH from wherever), Complex II (from FADH2 from TCA), Glycerol 3-phosphate dehydrogenase (from FADH2 glycerol 3-phosphate shuttle in glycolysis), and ETF (from β-oxidation) dump e-s onto CoQ. CoQ shuttles e-s to Complex III (another H+ pump) then to cytochrome C then to Complex IV (another pump; this is where O2 is needed + H+ —-> H20). The H+ ion gradient drives Complex V (ATP synthase).

237
Q

How are ROS generated in the mitochondria? How do mitochondria handle the ROS?

A

In hypoxic conditions the transfer of e-s slows down enough that O2 can react with either Complex I or III to form superoxide. O2- –(superoxide dismutase)–> H2O2 –(glutathione peroxidase)–> H2O. Glutathione peroxidase also leaves glutathione dimers in the oxidized state, and NADPH regenerates them.

238
Q

nicotinamide nucleotide transhydrogenase

A

In the mitochondria, turns a small portion of NADH into NADPH for the purpose of regenerating reduced glutathione.

239
Q

amytal

A

Barbiturate, blocks e- flow in Complex I of ETC (similar to rotenone)

240
Q

rotenone

A

Insecticide, blocks flow of e-s through Complex I of ETC (just like amytal).

241
Q

Antimycin A

A

Blocks flow of e-s from cytochrome b to c1 (ie blocks flow from Complex III of ETC).

242
Q

cyanide

A

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like CO and azide).

243
Q

azide

A

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like CO and cyanide).

244
Q

CO in the ETC

A

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like cyanide and azide).

245
Q

oligomycin

A

“Plugs” the H+ pump of ATP synthase, preventing charge equalization and inhibiting e- flow in ETC.

246
Q

Explain this image of rotenone inhibition of ETC:

A

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding rotenone inhibits Complex 1, stopping O2 usage. Add succinate and O2 usage resumes because succinate DH uses FADH2 which bypasses Complex I. ADP is depleted and ETC stops again.

247
Q

Explain this image of Antimycin A inhibition of ETC:

A

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding Antimycin A inhibits Complex III, stopping ETC. Succinate does not bypass Complex III, but ascorbate (vitamin C) can donate e-s to cytochrome C in vitro, so ATP production resumes until ADP is depleted.

248
Q

Explain this image of cyanide/azide/CO inhibition of ETC:

A

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding cyanide/CO/azide blocks ATP synthase, so nothing is able to get ATP synthesis to resume.

249
Q

2,4-dinitrophenol (DNP)

A

Powerful uncoupler of oxidative phosphorylation.

250
Q

What does it mean to “uncouple” oxidative phosphorylation?

A

Inhibit ATP synthesis (and increase heat production) but have no effect on electron transport or oxygen consumption. They “smuggle” protons back across the inner mitochondrial membrane after they’ve been pumped in the ETC.

251
Q

thermogenin (UCP1)

A

Physiological uncoupler of oxidative phosphorylation. Many hibernating animals express this and it keeps them warm.

252
Q

How do we get Pi and ADP into the mitochondrial matrix to make ATP?

A

Pi enters using H+ symport (thanks to the pumps). ADP enters using ATP/ADP antiport.

253
Q

Outline the process of lypolysis.

A

Perilipin is phosphorylated by PKA causing it to open up and give HSL access to the triacylglycerol inside. HSL removes the first FFA from TG, other lipases release the other 2.

254
Q

perilipin

A

Protein that coats lipid storage droplets. Is phosphorylated by PKA causing it to open up and give HSL access to the triacylglycerol inside.

255
Q

hormone-sensitive lipase (HSL)

A

Activated when glucagon causes cAMP rise in cells and PKA phophorylates HSL. HSL releases the first of the three FFA from TG. HSL is inactivated when insulin causes phosphodiesterase to remove cAMP and lipase phosphatase to dephosphorylate HSL.

256
Q

Outline the steps of the carnitine cycle.

A

The FA is brought into the intermembrane space where it is converted to Acyl-CoA. Acyl-CoA + carnitine –(carnitine-palmitoyl acyltransferase 1)–> CoA + acyl-carnitine. Acyl-carnitine can cross the other lipid layer and is reconverted to acyl-CoA by CPT2, and it can then undergo β-oxidation.

257
Q

carnitine-palmitoyl acyltransferase

A

Allows transport of FFAs from the cytosol through the membrane and the intermembrane space into the mitochondrial matrix.

258
Q

Outline the steps of β-oxidation.

A

Acyl-CoA dehydrogenase reduces FAD to put a double bond in the β position on the acyl group (ie CoA-S-CO-αC-βC). Water is added accross the double bond, adding a hydroxyl group to the βC. Next, another dehydrogenase uses NAD+ to oxidize the hydroxyl to a ketone group. Finally, a thiolase attacks the ketone and knocks off acetyl-CoA, reducing the length of the FA chain by 2C.

259
Q

What are the 4 levels of lipid metabolism that are regulated?

A

1) lipolysis, 2) FFA entry into mitochondria (malonyl-CoA inhibits carnitine-palmitoyl acetyltransferase), 3) availability of coenzymes for β-oxidation (eg alcohol uses up NAD+), and 4) glycerogenesis (FFA recycling).

260
Q

Outline the net reaction of the synthesis of palmitic acid from acetyl-CoA.

A

8 Acetyl-CoA + 14 NADPH + 14 H+ + 7 ATP —-> Palmitate + 14 NADP+ + 7 ADP + 7 Pi + 8 CoA-SH + 6 H2O. Overall, fatty acid synthesis is a reductive process that requires energy.

261
Q

Outline the generation of Acetyl-CoA and NADPH for fatty acid synthesis.

A

Glucose –(glycolysis)–> pyruvate –(enters mitochondrion)–> pyruvate –(pyruvate carboxylase and dehydrogenase)–> OAA and acetyl-CoA —-> citrate –(leaves mitochondrion)–> citrate + ATP –(citrate lyase)–> OAA + acetyl CoA. Acetyl-CoA is used for FA synthesis, OAA gets recycled in a process that generates NADPH (OAA + NADH –(cytosolic malate dehydrogenase)–> NAD+ + malate; malate + NADP+ –(malic enzyme)–> pyruvate + NADPH + CO2). The pentose phosphate pathway also produces NADPH.

262
Q

Summarize fatty acid synthesis from acetyl-CoA.

A

Acetyl-CoA –(acetyl-CoA carboxylase + biotin)–> malonyl-CoA. With the help of the ACP carrier protein and the reductive hep of NADPH, FA synthase joins the malonyl-CoA molecules together, extending FAs 2 carbons at a time until the 16 carbon palmitoyl-CoA is achieved. Further elongation or desaturation occurs in the ER.

263
Q

Explain the function and regulation of acetyl-CoA carboxylase.

A

A biotin-dependent enzyme (carboxylase) that converts acetyl-CoA to malonyl-CoA during FA synthesis. Glucagon inactivates via phosphorylation (and degradation of the large enzyme polymers), insulin activates via dephosphorylation. Citrate (present when insulin is present) activates it by facilitating it’s polymerization, while its product malonyl-CoA inhibits it.

264
Q

ACP

A

(acyl carrier protein) An analog of CoA that is the carrier of acyl molecules during energy degradative metabolism. During FA synthesis, it binds malonyl CoA to help it continue the FA synthesis process.

265
Q

citrate lyase

A

Under insulin activation, converts cytosolic citrate into acetyl-CoA for FA synthesis.

266
Q

malonyl-CoA

A

The substrate used by FA synthase. Produced from acetyl-CoA by acetyl-CoA carboxylase under insulin activity. Accumulation of malonyl-CoA can inhibit CPTI to limit further breakdown of FAs.

267
Q

Why are some FAs resynthesized into TGs after release?

A

It appears to be the body’s way to limit FA release to avoid toxic accumulation.

268
Q

lipoprotein lipase

A

Breaks down the fat in VLDL or chylomicrons, facilitates the release of FA from lipoprotein into the target (fat or muscle tissue).

269
Q

glycerol kinase

A

Present only in the liver, allows liver to turn glycerol to glycerol-3-phosphate which is necessary in the process of TG synthesis. Does NOT need insulin for this process.

270
Q

Outline the net reaction of the synthesis of palmitic acid from acetyl-CoA.

A

8 Acetyl-CoA + 14 NADPH + 14 H+ + 7 ATP —-> Palmitate + 14 NADP+ + 7 ADP + 7 Pi + 8 CoA-SH + 6 H2O. Overall, fatty acid synthesis is a reductive process that requires energy.

271
Q

Outline the generation of Acetyl-CoA and NADPH for fatty acid synthesis.

A

Glucose –(glycolysis)–> pyruvate –(enters mitochondrion)–> pyruvate –(pyruvate carboxylase and dehydrogenase)–> OAA and acetyl-CoA —-> citrate –(leaves mitochondrion)–> citrate + ATP –(citrate lyase)–> OAA + acetyl CoA. Acetyl-CoA is used for FA synthesis, OAA gets recycled in a process that generates NADPH (OAA + NADH –(cytosolic malate dehydrogenase)–> NAD+ + malate; malate + NADP+ –(malic enzyme)–> pyruvate + NADPH + CO2). The pentose phosphate pathway also produces NADPH.

272
Q

Summarize fatty acid synthesis from acetyl-CoA.

A

Acetyl-CoA –(acetyl-CoA carboxylase + biotin)–> malonyl-CoA. With the help of the ACP carrier protein and the reductive hep of NADPH, FA synthase joins the malonyl-CoA molecules together, extending FAs 2 carbons at a time until the 16 carbon palmitoyl-CoA is achieved. Further elongation or desaturation occurs in the ER.

273
Q

Explain the function and regulation of acetyl-CoA carboxylase.

A

A biotin-dependent enzyme (carboxylase) that converts acetyl-CoA to malonyl-CoA during FA synthesis. Glucagon inactivates via phosphorylation (and degradation of the large enzyme polymers), insulin activates via dephosphorylation. Citrate (present when insulin is present) activates it by facilitating it’s polymerization, while its product malonyl-CoA inhibits it.

274
Q

ACP

A

(acyl carrier protein) An analog of CoA that is the carrier of acyl molecules during energy degradative metabolism. During FA synthesis, it binds malonyl CoA to help it continue the FA synthesis process.

275
Q

citrate lyase

A

Under insulin activation, converts cytosolic citrate into acetyl-CoA for FA synthesis.

276
Q

malonyl-CoA

A

The substrate used by FA synthase. Produced from acetyl-CoA by acetyl-CoA carboxylase under insulin activity. Accumulation of malonyl-CoA can inhibit CPTI to limit further breakdown of FAs.

277
Q

Why are some FAs resynthesized into TGs after release?

A

It appears to be the body’s way to limit FA release to avoid toxic accumulation.

278
Q

lipoprotein lipase

A

Breaks down the fat in VLDL or chylomicrons, facilitates the release of FA from lipoprotein into the target (fat or muscle tissue).

279
Q

glycerol kinase

A

Present only in the liver, allows liver to turn glycerol to glycerol-3-phosphate which is necessary in the process of TG synthesis. Does NOT need insulin for this process.

280
Q

adenine vs adenosine

A

Adenine is the nitrogenous base, adenosine is the ribonucleotide with the sugar and phosphate added on.

281
Q

Where does purine synthesis mostly occur?

A

In the liver.

282
Q

Briefly outline the synthesis of purines. How many ATP are utilized?

A

First, Ribose-5-phosphate + ATP –(PRPP synthetase)–> PRPP +AMP. Then PRPP + glutamine –(PRPP amidotransferase)–> phosphoribosylamine + glutamate. Phosphoribosylamine undergoes 7 more modifications to form inosine monophosphate. 4 ATP are used up in this process.

283
Q

inosine monophosphate (IMP)

A

Formed as the product of 9 steps of metabolism of ribose-5-phosphate in the synthesis of purines.

284
Q

IMP dehydrogenase

A

Turns IMP into xanthosine monophosphate, which can then be converted to GMP. Inhibited by mycphenolic acid.

285
Q

adenylosuccinate synthetase

A

Turns IMP into adenylosuccinate, which is then converted into AMP.

286
Q

How are NMPs converted to NDPs?

A

Adenylate kinase or guanylate kinase phosphorylate them, BOTH using ATP.

287
Q

adenylate kinase

A

Converts AMP +ATP —-> 2 ADP

288
Q

guanylate kinase

A

Converts GMP + ATP —-> GDP + ADP

289
Q

nucleoside diphosphate kinases

A

Nonspecifically convert NDPs to NTPs using ATP.

290
Q

Where can purine synthesis be regulated? (3 places)

A

PRPP synthetase and PRPP amidotransferase can both be inhibited by purine nucleotides (product inhibition). Also, reactions from IMP to NMPs (ie adenylosuccinate synthetase and IMP dehydrogenase) are inhibited by NMPs.

291
Q

Outline purine degradation.

A

AMP needs to be deaminated (by either AMP deaminase or adenosine deaminase) and dephosphorylated (by 5’-nucleotidase) to inosine. Purine nucleoside phosphorylase uses a Pi to cleave inosine into ribose-1-phosphate and hypoxanthine, after which xanthine oxidase uses FAD to oxidize hypoxanthine to xanthine and then again to uric acid. Guanine on the other hand, does not need to be deaminated, just dephosphorylated (5’-nucleotidase) and cleaved from the ribose (purine nucleoside phosphorylase) to be freed, and then guanine deaminase turns it straight into xanthine, which is oxidized by xanthine oxidase to uric acid.

292
Q

How do we salvage dietary and turnover purines?

A

Adenine phosphoribosyltransferase (APRT) and Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) turn purine bases into nucleotides. Both use PRPP as the source of the ribose-5-phosphate group.

293
Q

Lesch-Nyhan syndrome

A

X-linked recessive HGPRT deficiency; results in build-up of PRPP and uric acid (and increased de novo purine synthesis), and decreased levels of AMP and GMP. Characterized by neurological features like self-mutilation and involuntary movements/grimacing.

294
Q

Outline the steps of pyrimidine synthesis from glutamine to CTP.

A

Glutamine + {CO2 + 2 ATP} –(carbamoyl phosphate synthetase II)–> {glutamate + 2 ADP + Pi} + carbamoyl phosphate + aspartate –(aspartate transcarbamoylase)–> N-carbamoyl-aspartate –(dihydroorotase)–> L-dihydroorotate + NAD+ –(dihydroorotate dehydrogenase)–> {NADH} + orotate + PRPP –(orotate phosphoriboyltransferase)–> oritidine monophosphate –(oritidylate decarboxylase)–> uridine monophosphate —-> UDP —-> UTP + {glutamine + ATP} –(CTP synthetase)–> {glutamate + ADP + Pi} + CTP!!

295
Q

CPSI vs CPS II

A

CPSI is in mitochondria for the urea cycle (uses ammonia) and is activated by N-acetyl-glutamate. CPSII is in the cytosol for pyrimidine synthesis (uses glutamine) and is activated by ATP but inhibited by UTP.

296
Q

Outline the general steps of pyrimidine degradation.

A

Deamination (only in the case of cytidine to uridine); nucleoside phosphorylase cleavage of the sugar (turning uridine to uracil or 2-deoxythymidine to thymine); reduction by NADPH; ring cleavage by water; hydrolysis by water to release CO2 and NH3. The products (β-alanine and β-aminoisobutyrate) are excreted in the urine.

297
Q

What is the product of cytidine degradation?

A

β-alanine

298
Q

What is the product of 2-deoxythymidine degradation?

A

β-aminoisobutyrate

299
Q

How are ribonucleosides converted to deoxyribonucleosides? (what enzyme)

A

Ribonucleotide reductase* uses NADPH to reduce a ribonucleotide diphosphate to 2-deoxyribonucleoside. (Thymine has its own enzyme, thymidylate synthase, whuch methylates dUMP to dTMP)

300
Q

How is the “T” deoxyribonucleotide synthesized? (what enzyme)

A

Thymidylate synthase* adds a methyl group to dUMP (uracil), making it dTMP (thymine)

301
Q

Explain ribonucleotide reductase structure/regulation.

A

Ribonucleotide reductase has specificity sites (whatever is bound increases production of itself?), activity sites (to regulate; ATP activates, dATP inhibits), and reduction sites (where the NDP is reduced to dNDP). Is inhibited by hydroxyurea

302
Q

azaserine

A

Glutamine antagonist (inhibits purine and pyrimidine synthesis) like acivin.

303
Q

acivicin

A

Glutamine antagonist (inhibits purine and pyrimidine synthesis) like azaserine

304
Q

methotrexate

A

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.

305
Q

trimethoprim

A

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.

306
Q

pyrimethamine

A

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.

307
Q

5-fluorouracil

A

Inhibits thymidylate synthase, reducing dTMP/inhibiting pyrimidine synthesis. Can also be incorporated into DNA and stop synthesis.

308
Q

hydroxyurea

A

Antineoplastic drug that inhibits ribonucleotide reductase.

309
Q

Gout

A

Caused by excess uric acid, which precipitate in the joints. Can be due to HGPRT deficiency or glucose-6-phosphatase deficiency (decreases gluconeogenesis, which increases pentose phosphate pathway, which increases ribose-5-phosphate, which increases PRPP, which increases purine synthesis) . Also related to lead contaminants in alcohol (lead causes kidney damage and decreased excretion of uric acid in urine) or excessive sugary beverages.

310
Q

tophi

A

Precipitates of uric acid in gout

311
Q

allopurinol

A

Inhibits xanthine oxidase (its metabolite alloxanthine plugs the enzyme)

312
Q

severe combined immunodeficiency (SCID)

A

(Adenosine deaminase deficiency) Presents within first month of life; patients lack both T cell and B cell immunity. Treatment involves bone marrow transplant.

313
Q

Once the NH3 is removed from amino acids during degradation, what is the final fate of the nitrogen-free intermediate?

A

It can be turned to glucose, to ketone bodies, or broken down to CO2 and H2O.

314
Q

Describe the normal adult amino acid pool equilibrium.

A

Our pool of AAs fed by the diet (~100g/day) and an equilibrium exists between the AA pool and the body protein pool (~250-300g/day). AAs can also be degraded (~100g/day) to ammonia and nitrogen-free intermediates.

315
Q

How does pregnancy affect the AA pool equilibrium?

A

Increase in dietary protein to synthesize more body protein.

316
Q

How does protein deficiency affect the AA pool equilibrium?

A

Less comes in so less can go to make protein, even though it’s getting broken down at the same rate.

317
Q

How does essential AA deficiency affect the AA pool equilibrium?

A

Lots of protein can come into the AA pool but little can be used for body protein, so there’s an increase in urea production.

318
Q

How do wasting disease, burns, and trauma affect the AA pool equilibrium?

A

Lots of body protein is broken down into the AA pool, so there’s excess of urea production as well.

319
Q

Which amino acids can be synthesized by humans?

A

Ala, Asp, Asn, Glu, Ser

320
Q

Which amino acids are “conditionally” essential (can be synthesized only at some stages)?

A

Arg, Cys, Gln, Gly, Pro, Tyr

321
Q

Which amino acids can never be synthesized by humans?

A

His, Iso, Leu, Lys, Met, Phe, Thr, Try, Val

322
Q

How are the “other” amino acids (not the main 20) synthesized

A

Post-translational modification of AAs in protein.

323
Q

Which are “stabilizing” N-terminal AAs?

A

Met, Ser, Gly, Ala, Thr, Val

324
Q

Which are “destabilizing” N-terminal AAs?

A

Arg, Lys, Leu, Phe, Asp, Tyr

325
Q

What is the PEST sequence?

A

A protein turnover sequence: Pro Glu Ser Thr.

326
Q

What are the differences between lysosomal and proteosomal degradation?

A

LYSOSOMAL: energy independent, primarily extracellular proteins. PROTEOSOMAL: energy-dependant, primarily internal proteins tagged via ubiquitin.

327
Q

Outline the process of ubiquitination.

A

Ubiquitin –(E1 + ATP)–> ubiquitin-S-E1 –(E2)–> ubiquitin-S-E2 + target protein-Lys-NH2 –(E3)–> target-Lys-NH-ubiquitin.

328
Q

bortezomib

A

Proteasome inhibitor, approved for myeloma treatment.

329
Q

Outline protein degradation in the stomach.

A

Gastrin is produced by stomach G cells in response to protein-rich meal; activates chief cells (secrete pepsinogen) and parietal cells (secrete HCl which denatures proteins and also activates pepsinogen autocatalytic cleavage); allowing pepsin to start to cleave proteins (ie formation of peptone).

330
Q

Outline protein degradation in the small intestine.

A

The low pH triggers pancreatic release of secretin (stimulates the pancreas to secrete bicarbonate) and cholecystokinin (stimulates release of trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidases A & B). Enteropeptidase activates trypsin, trypsin activates the other zymogens.

331
Q

How are AAs pumped from the intestinal lumen to the serosal side of the epithelium?

A

Na+ symport (gradient maintained with an NA/K pump) into the epithelial cell, then facilitated transport out.

332
Q

Kwashiorkor syndrome

A

Caused by dietary protein deficiency, leading to albumin deficiency (among other things). Characterized by fluid leakage into abdomen: distended abdomen.

333
Q

What effect can cystic fibrosis have on protein metabolism? What is the treatment?

A

Defective chloride channels cause inspissations of pancreatic exocrine secretion, obstructing enzyme release. Treatment is supplementation of pancreatic enzymes with each meal.

334
Q

cystinuria

A

Patients inherit defective transport of cystine (sulfide-linked cysteines) and basic AAs (lysine, arginine, ornithine) across the brush-border membranes of intestinal and renal cells. Cystine isn’t very soluble so it can then form kidney stones.

335
Q

Hartnup disease

A

Patients inherit defective transport of neutral AAs across intestinal and renal epithelial cells. This results in deficiency of essential amino acids, which in part causes failure to thrive, photosensitivity, and tremors.

336
Q

Altered transport of which AAs has been implicated in schizophrenia and bipolar disorder? Why?

A

Tyrosine and tryptophan; these are precursors for dopamine and serotonin.

337
Q

What are the sources of ammonia in the body?

A

Amino acids, glutamine, bactieral urease, dietary and endogenous amines, and nucleotide metabolism.

338
Q

What enzymes release ammonia from amino acids?

A

Aminotransferase and glutamate dehydrogenase

339
Q

What enzymes release ammonia from glutamine? Where in the body does this occur and what happens to the ammonia?

A

Renal glutaminase and glutamate dehydrogenase. This happens in the kidney, and the ammonia is excreted in the urine.

340
Q

What bacterial enzyme releases ammonia? Where in the body does this occur and what happens to the ammonia?

A

Bacterial urease cleaves any urea that is leaked into the intestine. This is abosorbed in the small intestine via the portal vein and broken down in the liver, or else it is lost in feces.

341
Q

What enzymes release ammonia from amines (like neurotransmitter monoamines)?

A

Amine oxidases

342
Q

What are the two sources of urea nitrogen?

A

Ammonia and aspartate

343
Q

pyridoxal phosphate

A

Coenzyme that is covalently linked to a lysine in the aminotransferase active site. Eg carries the NH3 from glutamate to OAA forming aspartate.

344
Q

Outline the flow of nitrogen from amino acids to ammonia and urea.

A

Amino acids pass their NH3 to pyruvate forming alanine via transaminases. Ala passes the NH3 to α-ketoglutarate via alanine transaminase, forming glutamate. Glutamate can either give off ammonium (via glutamate dehydrogenase) or can pass the NH3 to OAA forming aspartate, which is processed into urea.

345
Q

Other than transamination, what additional mechanisms of amino acid deamination exist?

A

Oxidative deamination (via oxidases that use FMN) and nonoxidative deamination of hydroxyamino acids (via dehydratases)

346
Q

glutamate dehydrogenase (GDH)

A

GDH reduces α-ketoglutarate to glutamate and vice versa.

347
Q

glutaminase

A

Breaks down the glutamine that tissues send to the liver into glutamate and NH3, which then enters the urea cycle.

348
Q

Track the path of ammonia in the glucose-alanine cycle.

A

In muscles, NH3 + α-ketoglutarate –(glutamate dehydrogenase)–> glutamate; NH3 is passed to pyruvate (alanine aminotransferase) forming alanine; alanine is sent to the liver; NH3 passed back to α-ketoglutarate (alanine aminotransferase) forming {pyruate} and glutamate –(glutamate dehydrogenase)–> NH3 is released, then converted to urea.

349
Q

What is a normal level of blood urea nitrogen?

A

250-700 uM/I.

350
Q

Outline the urea cycle, starting with NH4+ in the mitochondrion.

A

[image]

351
Q

carbamoyl phosphate

A

In the mitochondria, is the product of ammonium combination with HCO3- and cleavage of 2 ATP (via carbamoyl phosphate synthetase). It’s then combined with ornithine to form citrulline (via ornithine transcarbamoylase).

352
Q

carbamoyl phosphate synthetase I

A

Catalyzes the combination of NH4+, HCO3-, and 2 ATP into carbamoyl phosphate. Deficiency leads to high blood ammonia and low everything else in the UC cycle.

353
Q

ornithine

A

Is the product of the cleavage of urea from arginine in the cytosol. Is then imported into the mitochondrion to combine with carbamoyl phosphate (in exchange for H+ or

354
Q

ornithine transcarbamoylase

A

Catalyzes the combination of ornithine and carbamoyl phosphate in the mitochondria. Deficiency leads to high ammonia, low arginine, low citrulline, and high orotate.

355
Q

citrulline

A

Product of the combination of carbamoyl phosphate and ornithine (via ornithine transcarbamoylase) in the mitochondrion. Is exported from the mitochondrion to combine with aspartate to form argininosuccinate (via argininosuccinate synthetase).

356
Q

aspartate’s role in the urea cycle

A

Combines with citrulline to form argininosuccinate (via argininosuccinate synthetase).

357
Q

argininosuccinate synthetase

A

Catalyzes the formation of argininosuccinate from citrulline and aspartate (and ATP). Deficiency leads to high ammonia, low aarginine, high citrulline, and low orotate.

358
Q

argininosuccinate

A

Formed in the urea cycle by argininosuccinate synthetase from aspartate and citrulline. Broken down into fumarate and arginine by argininosuccinate lyase.

359
Q

fumarate

A

Component of both the TCA cycle and the urea cycle. In the urea cycle, produced by arginosuccinate lyase activity. Can be hydrated to malate and brought into the mitochondria through the malate shuttle and reenter the TCA cycle.

360
Q

arginine (urea cycle)

A

Produced by arginosuccinate lyase activity. Broken down by arginase to urea and ornithine. Stimulates N-acetylglutamate synthase, which activates CPSI and initiates the urea cycle. Can be used to treat UCDs (except for arginase deficiencies).

361
Q

argininosuccinate lyase

A

Catalyzes the breakdown of arginosuccinate into fumarate and arginine. Deficiency causes high ammonia, low arginine, MODERATE CITRULLINE, and low orotate.

362
Q

arginase

A

Catalyzes the breakdown of arginine to urea and ornithine. Is ONLY expressed int he liver, so only liver can do the urea cycle. Deficiency leads to moderate ammonia in blood, high arginine, low citrulline, and low orotate.

363
Q

What is the clinical consequence of ornithine deficiency?

A

Hyperammonemia and elevated urine orotate (since the backed-up carbamoyl phosphate is converted to orotic acid.

364
Q

carbamoyl phosphate synthetase II

A

Involved in pyrimidine synthesis. Not to be confused with CPSI, which is involved in the urea cycle.

365
Q

What activates CPSI in the urea cycle?

A

N-acetylglutamate

366
Q

Which is the rate limiting step of the urea cycle?

A

CPSI

367
Q

Which urea cycle enzyme deficiency does NOT cause symptomatic UCD? What are its consequences?

A

Arginase: causes moderate blood ammonia, high arginine, low citrulline, and low orotate.

368
Q

benzoate

A

Used to treat hyperammonemia in liver cirrhosis nad UC enzyme deficiencies. Combines with glycine to form hippuric acid and is cleared by the kidneys.

369
Q

phenylacetate

A

Used to treat hyperammonemia in liver cirrhosis nad UC enzyme deficiencies. Conjugates with glutamine and is cleared by the kidneys.

CMB (8 decks)

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