SFM Quiz 1 Flashcards
(148 cards)
1
Q
the body’s inability to easily digest Lactose due to genetic deficiency of lactase, with an age-dependent decrease in production of the enzyme (infant possess sufficient quantities). Results in gas, belly pain, and bloating within 2 hours of consuming lactose.
A
lactose intolerance
2
Q
- Nutritional reservoir of carbs in plants
Polysaccharide of glucose - Found in fruits and vegetables
Disaccharide of glucose and fructose - Plant origin
- Major dietary carbohydrates of animal origin
Disaccharide of glucose and galactose
A
- Starch
- Sucrose
- Dietary fiber
- Lactose
3
Q
Monosaccharides
A
Glucose, fructose, galactose, ribose
4
Q
Disaccharides
A
Maltose (alpha 1,4)
lactose (beta 1,4)
sucrose (alpha 1, beta 2)
5
Q
Oligosaccharides
A
Glycolipids and glycoproteins
6
Q
Polysaccharides
A
Glycogen: alpha 1,4 alpha 1,6
starch: amylose (alpha 1,4) amylopectin (alpha 1,4 alpha 1,6)
Cellulose: beta 1,4
7
Q
The ___ stores lipid-emulsifying bile. Nonideal bile composition including too much cholesterol and too little bile salts cause formation of crystalline ___ in the ___. Continued disturbances in metabolism can lead to malabsorption (____) and fat-soluble vitamin deficiencies. Oral chenodeoxycholic acid can help dissolve ____.
A
Gall bladder
Gall stones
Gall bladder
steatorrhia
8
Q
omega 3
omega 6
A
Linolenic acid
Linoleic and Arachidonic acids
9
Q
exergonic
A
ΔG < 0, spontaneous (energy producing)
10
Q
endergonic
A
ΔG > 0, non-spontaneous (energy consuming)
11
Q
Mass action (Le Chatelier’s principle)
A
Sign of ΔG dependent on Keq
↑ [reactants], ↓ [products]
12
Q
decrease pH
decrease CO2
decrease bicarb
hyperventilation
A
Metabolic acidosis
13
Q
decrease pH
increase CO2
increase bicarb
increase renal bicarb reabsorption
A
Respiratory acidosis
14
Q
increase pH
increase CO2
increase bicarb
hypoventilation
A
Metabolic alkalosis
15
Q
increase pH
decrease CO2
decrease bicarb
decrease renal bicarb reabsorption
A
Respiratory alkalosis
16
Q
Enzymes
A
Biological catalysts Lower activation energy (Ea) Increase reaction rate No effect on ΔG Facilitate reaction occurring by binding substrates and converting to products
17
Q
Catalytic triad
A
acidic, basic, nucleophilic
18
Q
Found in the parietal cells that line the gastric lumen.
Pump H+ into the lumen where it combines with Cl- to form HCl.
Conditions like ulcers, indigestion, heartburn require decrease in ___ thus _____ are prescribed (Omeprazole, lansoprazole, esomeprazole).
Reduced ___ production causes _____ which can reduce absorption of nutrients, increase in sensitivity to food poisoning, reduction in gastric enzyme efficiency, particularly pepsin, gastric amylase, gastric lipase.
A
Gastric acid
proton pump inhibitors
HCl
hypochlorhydria
19
Q
No effect on Vmax
Increase in Km
Larger substrate concentration needed to achieve ½ Vmax
A
Competitive inhibitors
substrate binding
20
Q
Examples of Competitive inhibitors
A
Malonate=succinate dehydrogenase sulfanilamide=dihydropteronate synthetase methotrexate=dihydrofolate dehydrogenase captopril=angiotensin-converting enzyme allopurinol=xanthanine oxidase
21
Q
Decrease in Vmax
Unchanged Km
Inhibitor effects cannot be overcome by increase in substrate concentration
A
Noncompetitive inhibitors
binds to E and ES
22
Q
Examples of Noncompetitive inhibitors
A
Physostigmine=acetylcholinesterase
allopurinol=xanthine oxidase
oxypurinol=xanthine oxidase
23
Q
Examples of Uncompetitive inhibitors
A
Lithium=inositol monophosphate
24
Q
Examples of Uncompetitive inhibitors
A
Lithium=inositol monophosphate
25
Decrease in Vmax
Unchanged Km (no affect on affinity)
Only overcome by synthesis of new enzymes
Enzyme inactivation
Destruction or covalent modification of key amino acid’s functional groups
26
Examples of Enzyme inactivation
Organophosphates=acetylcholinesterase
cyanide/sulfides=cytochrome c oxidase (complex IV)
aspirin=Prostaglandin synthase (COX1/2)
27
abdominal pain, sideroblastic anemia, irritability, headaches, impaired nervous system development, encephalopathy
Pb inhibits ALA dehydratase and ferrochelatase.
Ferrochelatase= involved in heme synthesis; coenzyme of hemoglobin
Administration of Ca-EDTA: Pb has a higher affinity for EDTA than Ca
Pb-EDTA excreted in urine
28
A 66 year-old female is seen in the ED in the late evening. She reports she has had “pressure” on her chest for the last few hours but denies overt chest pain; jaw, neck, shoulder or arm pain; shortness of breath (dyspnea); and sweating (diaphoresis). The pressure does not increase with exertion. History shows hyperlipidemia treated with diet and drugs and no familial history of heart disease. Heart rate and respiratory rates are elevated. Blood is drawn and sublingual nitroglycerin is given. An EKG is performed and the results are characteristic of ___. Cardiac biomarker assay reveals____, ____ (found in heart muscle) to__ ratio and ____.
MI
elevated CK
CK-MB to CK ratio
cTnI
29
Enzymes useful for diagnosis of disease
```
bone disease=alkaline phosphatase
obstructive liver disease=sorbitol dehydrogenase/lactate dehydrogenase
prostatic cancer=acid phosphatase
acute pancreatitis=amylase
muscular dystrophy=aldolase/ASH
liver disorder=CK-MM
```
30
```
Protein
Carbs
Fats
Alcohol
N-6 PUFA
N-3 PUFA
```
```
4kcal/g, 10-35%
4kcal/g, 45-65%
9kcal/g, 20-35%
7kcal/g
5-10%
.6-1.2%
```
31
Fiber
Plant polysaccharides – cellulose, gums, hemicellulose, & pectin
Not completely (if at all) by humans, “Does not contribute to caloric intake” (i.e., net carbs)
Soluble & insoluble
Slows gastric emptying, reduces glycemic index/load, makes food bulky/satiety, influences absorption and motility along GI tract.
20-35 g/day recommended
32
Conditional essential fatty acids
EPA, DHA
33
Digested products are absorbed into hepatic portal system
| Conditions and diseases involving absorption
Steatorrhia
| Crohn's disease
34
Caused by deficiency in the activity of an enzyme called Acid Sphingomyelinase (A-SMase).
A-SMase is a lysosomal enzyme which breaks down sphingomyelin (SM) into ceramide and phosphorylcholine.
Defective A-SMase leads to the accumulation of SM in lysosomes of liver, spleen, CNS, and bone marrow.
Leads to:
Enlargement of liver (hepatomegaly)
Enlargement of spleen (splenomegaly)
Causes neurological damage.
Hallmark “cherry red spot” in the eye.
Fatality – Type A, 85%, by 18 months of age.
Niemann-Pick disease
35
Outer sheet membrane lipids
Phosphatidylcholine
Sphingomyelin
Glycolipids
36
Inner sheet membrane lipids
Phosphatidylinositol
Phosphatidylserine (flips to outside, marker for apoptosis)
Phosphatidylethanolamine
37
Blood type O
H antigen
anti-A/B antibodies
*universal donor
38
Blood type A
A antigen
| anti-B antibodies
39
Blood type B
B antigen
| anti-A antibodies
40
Blood type AB
A,B antigens
no antibodies
*universal acceptor
41
disease in which there is incompatibility between blood of mother and fetus.
When mom is Rh- and fetus is Rh+, the mom produces antibodies during pregnancy. These cross placenta and attack the fetus. Risk is greater in subsequent pregnancies
Erythroblastosis fetalis
Hemolytic disease of the newborn
42
Associated with beta lipoproteinemia and advanced stages of alcoholic liver cirrhosis.
Chronic liver dysfunction impairs cholesterol metabolism by the liver, resulting in excess free cholesterol.
Elevated levels of cholesterol bound to rbc membrane.
Decreases fluidity and flexibility of membrane.
Creates rough thorny projections on the rbcs.
Such cells called acanthocytes.
Impaired deformability of rbcs.
Cause rbcs to break their membranes (lyse) as they pass through capillaries of spleen.
Spur cell anemia
43
Cholesterol + rigid membrane=
| Cholesterol + fluid membrane=
increase fluidity
| decrease fluidity
44
Autosomal recessive disorder.
Caused by defect in the transporter responsible for uptake of dimeric amino acid Cystine and other dibasic amino acids such as Arginine, Lysine, and Ornithine.
Results in formation of Cystine crystals or stones in the kidney (identified via a positive nitroprusside test).
Patients present with renal cholic (abdominal pain that comes in waves and is linked to kidney stones).
Cystinuria
45
Autosomal recessive disorder.
Caused by a defect in a transporter for non-polar or neutral amino acids (e.g., alanine, valine, threonine, leucine, tryptophan etc).
Transporter found primarily in kidneys and intestine.
Manifests in infancy as failure to thrive.
Clinical findings – intermittent cerebellar ataxia (lack of muscle coordination), nystagmus (rapid and repetitive eye movement), tremor, photodermatitis and photosensitivity.
Also known as pellagra-like dermatosis.
Triggered by sunlight, fever, drugs, or emotional or physical stress.
Period of poor nutrition almost always precedes an attack.
Hartnup disorder
46
Inhibit the Na+/K+-ATPase in cardiac myocytes.
Leads to increase in intracellular Na+
This impairs the activity of the secondary transporter called Sodium Calcium Exchanger (NCX) as NCX is coupled to the Na/K-ATPase.
Impairment of NCX leads to a secondary increase in Ca2+ in the sarco-endoplasmic reticulum.
Therapeutic use - congestive heart failure (CHF), atrial fibrillation, dysrhythmias.
Cardiac glycosides are extremely potent.
_____ slowly reduces the resting potential of neurons to zero
Common side effects: disturbed vision, confusion, and delirium
Cardiac glycosides souabain and the lipophilic drug digoxin act as cardiotonic (contraction-inducing) drugs.
Digitoxigenin
47
Autosomal recessive disorder.
Caused by mutation in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.
Results in defective CFTR protein which is misfolded and does not leave the ER after translation.
CFTR protein is a chloride ion channel that mediates the active transport of Cl- from inside cells to the outside in airways and sweat ducts
Thicker mucous and leaves the airways susceptible to bacterial infections.
Cystic Fibrosis
48
Ubiquitous but high expression in RBCs and brain
| High affinity
GLUT 1
| Km=1
49
Main transporter in liver
| Low affinity
GLUT 2
| Km=10
50
Main transporter in neurons
| - High affinity
GLUT 3
| Km=1
51
Present in skeletal muscle, heart, adipose tissue
| - Insulin dependent
GLUT 4
| Km=5
52
Exercise-induced muscle cramps and weakness
Hemolytic anemia
High bilirubin and jaundice
Symptoms can be mild; true incidence may be higher due to lack of recognition and diagnosis
Tauri disease
Deficiency in PFK-1
53
Since rbcs lack mitochondria, glycolysis is only mechanism for producing ATP.
Failure of glycolysis results in ATP deficiency.
Leads to disruption of ion gradients powered by ATP.
Causes reduced cell viability
Hemolytic anemia
54
Disorders that lead to hemolytic anemia
Phosphoglucose isomerase= autosomal recessive
Aldolase A= deletion
Triose phosphate isomerase=autosomal recessive
Pyruvate kinase=erythrocyte mutation
55
Brain during extreme starvation
ketone body utilization= beta-hydroxybutyrate
56
Diabetes Type I
| Diabetes Type II
Type I: loss of pancreatic beta cells
| Type II: loss of Beta cell function
57
Diabetes causes
mutations in GK and mitochondrial tRNAleu genes
aberrant conversion of proinsulin to mature insulin
defective insulin receptor
pancreatitis
trauma
infection
pancreatic carcinoma.
58
Autosomal recessive disorder.
Caused by mutation in GLUT 2 transporter (located in liver, pancreatic β cell, enterocytes and renal tubular cells).
Unable to take up glucose, fructose and galactose
Symptoms – failure to thrive, hepatomegaly, tubular nephropathy, abdominal bloating, and resistant rickets.
Fasting hypoglycemia, and postprandial hyperglycemia.
Treatment – vitamin D and phosphate, and uncooked corn starch (prevents spikes in blood sugar and provides sustained release of glucose).
Fanconi-Bickel syndrome
59
Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver
Glucose produced in liver transported back to RBC and muscle
Prevents lactate accumulation
Regenerates glucose
Cori cycle
60
Similar to Tarui disease in glycolysis
Presents in infancy or early childhood
Hypoglycemia, lactic acidosis, ketosis, apnea, hyperventilation (after fructose, glycerol or sorbitol)
F-1,6 BP deficiency
61
Occurrence of 1 in 100,000 live births
Inefficient release of free glucose into the bloodstream by the liver in gluconeogenesis and glycogenolysis
Patients exhibit marked fasting hypoglycemia, lactic acidosis, hepatomegaly due to buildup of glycogen, hyperlipidemia and potentially retarded growth.
von Gierke disease
deficiency in glucose-6-phosphatase
62
Fructose uptake
| Glucose/Galactose uptake
Fructose: GLUT5, GLUT2/5
| GLU/GAL:SGLT1, GLUT2
63
Polyol Pathway
Glucose reduced to sorbitol by Aldose reductase
| Sorbitol oxidized to fructose by Sorbitol dehydrogenase
64
Cells that lack ________ (kidneys, retina, Schwann cells) can accumulate sorbitol, which triggers water influx and causes swelling. Manifests as retinopathy, cataracts and peripheral neuropathy.
sorbitol dehydrogenase
65
Actions of (1) and (2) bypass the most important regulatory step in glycolysis, the (3)-catalyzed reaction.
G3P and DHAP are processed by glycolysis to pyruvate and acetyl CoA in an unregulated fashion.
Excess acetyl CoA converted to fatty acids, which can be transported to adipose tissue to form triacylglycerols, resulting in obesity.
Liver also begins to accumulate fatty acids, resulting in fatty liver.
Activity of the (1) and (2) can deplete the liver of ATP and inorganic phosphate, compromising liver function.
fructokinase
triose kinase
phosphofructokinase
66
Leads to accumulation of galactitol
| Failure to thrive, liver failure, sepsis, bleeding
Classic galactosemia
Deficiency in glucose 1P uridyltransferase (GALT)
67
Leads to accumulation of galactose and galactitol in blood and urine
Accumulation of galactitol in lens of eye leads to cataracts in early infancy.
Nonclassical galactosemia
Deficiency in galactokinase
68
Patients cannot synthesize and store glycogen
Rely on glucose in diet
Vulnerable to hypoglycemia when fasting (e.g., during sleep)
Have muscle cramps due to lack of glycogen in muscle
Need to eat frequently
GSD0
Deficiency in glycogen synthase
69
Impairs lysosomal glycogenolysis resulting in accumulation of glycogen in lysosomes.
Disrupts normal functioning of muscle and liver cells.
Progressive muscle weakness (myopathy) in body including heart and skeletal muscle.
Kids die of heart failure in infancy.
Enzyme replacement therapy being developed to treat this disease.
GSDII/Pompe disease
Deficiency in Acid Maltase aka acid α -glucosidase
70
Patients possess glycogen molecules with large number of short branches.
Light hypoglycemia and hepatomegaly.
GSDIII/Cori disease
Deficiency in α-1,6,-glucosidase (debranching enzyme).
71
Patients have long chain glycogen with fewer branches.
Causes enlargement of liver and spleen, scarring of liver tissue (cirrhosis).
Death by 5 years of age.
GSDIV/Anderson disease
Deficiency in glucosyl (4:6) transferase (branching enzyme)
72
Rate limiting step of glycogen breakdown
Patients unable to supply muscles with enough glucose
Have weakness, fatigue, muscle cramping, and muscle breakdown (Myoglobinuria)
Myoglobin appears in urine
Exercise intolerance
Patients recommended to reduce strenuous exercise
GSDV/McArdle disease
Deficiency in muscle glycogen phosphorylase
73
Prevents glycogen breakdown in liver, hence it accumulates in liver causing hepatomegaly.
Low blood glucose levels.
GSDVI/Hers disease
Deficiency in liver glycogen phosphorylase
74
Disorders with wide range of deficiencies in the enzymes and proteins involved in transport or breakdown of FA
Carnitine shuttle, acyl CoA dehydrogenases, trifunctional protein (TFP) (has activities of enoyl CoA hydratase, hydroxy acylCoA dehydrogenase and ketothiolase), last 3 steps of β degradation.
Wide ranging symptoms - mental retardation, neuropathy, adrenal insufficiency, hypoglycemia
Inherited as autosomal recessive
Several are screened for in newborns
Metabolic disorders of FA-oxidation
75
A disorder of FA-b-oxidation that impairs breakdown of MCFAs
Autosomal recessive
Incidence – 1:12,000, most prevalent in Northern European Caucasians
Leads to secondary carnitine deficiency, due to excessive excretion of MCA carnitines in urine
C8 FA accumulates in liver, poisonous, interferes with urea cycle, elevated levels of ammonia
Some MCFA undergo ω-oxidation forming MC dicarboxylic acids (leads to metabolic acidosis
Patients depend on glucose as energy source
Gluconeogenesis impaired due to low activity of pyruvate carboxylase (due to low ATP and low Acetyl CoA)
Hypoglycemia/sudden death without timely intervention
Most often brought on by periods of fasting or vomiting
Underdiagnosed cause of sudden death in infants
ID prior to the onset of symptoms excellent prognosis!
Treatment mainly preventative
Avoid fasting and other situations where the body relies on FA-b-oxidation to supply energy
MCAD deficiency
76
(1)– mild to moderate increase in ketone bodies.
Occurs in fasting, during pregnancy and in babies. Also after prolonged exercise and ketogenic diet.
(2) – occurs when glucagon/insulin ratio is increased, favoring FA breakdown.
Increased Aceyl CoA in hepatic mitochondria.
Increased gluconeogenesis - reduced oxaloacetate.
Increased Ketone Bodies.
Acetoacetate and b-Hydroxybutyrate are strong acids, lower blood pH, causing acidosis.
Increased excretion of acetoacetate and b-Hydroxybutyrate via urine.
Acetone exhaled via breath, fruity odor in individuals with uncontrolled diabetes.
Physiological ketosis
| Pathological ketoacidosis
77
Ketogenic A.A.
Leucine, Lysine
acetyl coa or acetoacetate
78
Ketogenic/Glucogneic A.A.
```
Phenylalanine
Isoleucine
Tryptophan
Tyrosine
Threonine
```
79
A.A.s that enter at: pyruvate
Cysteine
Tryptophan->Alanine
Threonine->Glycine->Serine
80
A.A.s that enter at: alpha-ketoglutarate
Proline
Histidine
Arginine
Glutamine
All are converted to Glutamate->alpha-ketoglutarate
81
A.A.s that enter at: succinyl-coa
Threonine
Methionine (Homocystinuria)
Valine
Isoleucine
82
A.A.s that enter at: fumarate
Phenylalaine->Tyrosine
83
A.A.s that enter at: oxaloacetate
Asparagine->aspartate
84
Pyruvate + Glutamate->Alanine + alpha-ketoglutarate
Oxaloacetate + Glutamate->Aspartate + alpha-ketoglutarate
Glutamine + H2O->Glutamate + NH3
```
alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Glutamine aminohydrolase (GA)
```
85
Vitamin required for transaminases
pyridoxyl-5'-phosphate (PLP) derivative of vitamin B6
86
defective metabolism of homocysteine
Hyperhomocysteinemia is a risk factor in atherosclerotic heart disease and stroke and can result in neuropsychiatric illness (vascular dementia, Alzheimer’s disease).
Also in eye lens dislocation, osteoporosis and mental retardation.
Vitamin supplementation can normalize plasma homocysteine levels in some cases
Hyperhomocystinuria, Homocystinuria
deficiency B6, B12, folic acid) or genetic defects in enzymes (cystathionine β-synthase)
87
rare autosomal diseases resulting from deficient ____ activity which results in ____ ketoaciduria.
Also accumulate in blood causing toxic effects on brain function and eventually mental retardation
may be restored with thiamine supplementation in mild forms
Mennonite, Amish
Maple syrup urine disease
deficient branched-chain α-keto acid dehydrogenase complex (BCKD)
Branched-chain amino acids present in the urine give the hallmark maple syrup smell.
Leucine, Isoleucine, Valine
88
musty odor in urine
disrupts neurotransmission and block amino acid transport in the brain as well as myelin formation, resulting in severe impairment of brain function
Phenylketonuria
PKU is caused by defects in the activity of phenylalanine hydroxylase (PAH)
Secondary PKU resulting from tetrahydrobiopterin deficiency (a cofactor of phenylalaninie hydroxlyase).
89
Tryptophan derivates
Serotonin->melatonin (PLP/Vitamin B6)
| Niacin->NADPH (Vitamin B6)
90
Serine derivatives
Acetylcholine
91
Glutamate derivatives
GABA
92
Tyrosine derivatives
Dopamine->Norepinephine->Epinephrine
Thyroid hormones
Melanin
93
decreased T3,T4 levels
Graves disease
94
defective tyrosinase
| partial or complete absence of pigmentation in skin, hair and eyes
Albinism
95
defective dopa decarboxylase
Parkinsonism
PLP/Vitamin B6
Carbidopa inhibits
96
Arginine derivatives
Arginine->creatine (CK-MB=diagnostic marker for MI)
Glycine
Methionine
97
```
High glycemic load
Inappropriate macronutrient composition
Incorrect fatty acid composition (saturated, low omega-3/omega-6)
Lack of micronutrient density
Acid-base imbalance
High Na/K ratio
Low fiber content
Chemical content
```
Western diet
98
(1) occur when intake is below what is required for an individual, often resulting in a well-described disease associated with the deficiency.
(2) occur when intake is below what is optimal for health, making an individual susceptible to disease
1. Deficiencies
| 2. Insufficiencies
99
Vitamin D function
GI tract: induces synthesis of Ca2+ binding proteins and promotes Ca2+ absorption
Kidneys: stimulates reabsorption of Ca2+ and phosphate
Bone: osteoclast activation → bone resorption
100
Vitamin D
Vitamin D2 (ergocalciferol)
Vitamin D3 (cholecalciferol) – greater bioavailability
Calcidiol (25-hydroxy vitamin D): storage form in liver [measured, > 20 ng/mL (50 nmol/L)]
Calcitriol: active vitamin D (1,25-dihydroxy vitamin D); formed in kidney in response to PTH Function (↑ Ca2+ and phosphate)
101
Childhood rickets (skeletal abnormalities)
Adults osteomalacia (fewer deformities)
Mild deficiency → Chvostek’s/Trousseau’s signs
Severe deficiency → hypocalcemic tetany
Breast-fed only infants → vitamin D deficiency
Signs and symptoms of rickets may include:
Delayed growth
Pain in the spine, pelvis and legs
Muscle weakness
Bowed legs
Thickened wrists and ankles
Breastbone projection
Vitamin D deficiency
102
Vitamin D/Ca+2 supplementation
Bioavailability of choices is important
Vitamin D3 > Vitamin D2
Calcium citrate > calcium carbonate but more expensive; consume calcium carbonate with meals to boost absorption; do not use calcium carbonate with medications for peptic/gastric ulcers use calcium citrate
Works together with Vitamin D
Estimate calcium intake # of dairy servings/day by 300 mg
103
conversion of pyruvate to acetyl CoA mediated by pyruvate dehydrogenase
Branched chain amino acids
Transketolase (PPP shunt)
Thiamine (B1)
104
Wernicke’s encephalopathy: (acute) ataxia, nystagmus, ophthalmoplegia, confusion
Korsakoff’s syndrome: (chronic) psychosis, confabulation
Dry beriberi: muscle wasting, partial paralysis
Wet beriberi: peripheral edema, cardiac failure
Vitamin B1 (Thiamine) deficiency
105
FAD/FMN
Coenzyme for several dehydrogenases
Involved in oxidation/reduction reactions
Vitamin B2 (Riboflavin)
106
Usually undetected, accompanied by other deficiencies, malabsorption issues
Clinical manifestations
Sore throat, hyperemia of pharyngeal mucous membranes, edema of mucous membranes, chelititis, stomatitis, glossitis, normocytic-normochromic anemia, seborrheic dermatitis.
Riboflavinosis (Vitamin B2 deficiency)
107
NAD(H) and NADP(H)
| Metabolism reactions for carbohydrates, fatty acids, and proteins (tryptophan)
Vitamin B3 (Niacin)
108
Diarrhea, Dementia, Dermatitis, Death
Pellagra
109
: impaired AA absorption from intestines and reabsorption in kidneys → tryptophan deficiency → niacin deficiency
Hartnup disease
110
Pellagra: Diarrhea, Dementia, Dermatitis, Death (4Ds)
Malnutrition from alcoholism, bariatric surgery, AN, or malabsorption diseases Clinical manifestations:
Hartnup disease: impaired AA absorption from intestines and reabsorption in kidneys → tryptophan deficiency → niacin deficiency
Toxicity – flushing of the face, nausea, vomiting, liver changes, constipation (1000-3000 mg/d dose range; RDA 12-16 mg/d)
Vitamin B3 (Niacin) deficiency
111
Synthesis of coenzyme A (CoA):
All reactions that involve CoA – vit A, D, cholesterol steroids, heme A, fatty acids, carbs, amino acids/proteins.
First step in TCA cycle by forming citrate
Pantothenic acid (Vitamin B5)
112
Dermatitis, numbness, paresthesia and dysesthesias (“burning feet syndrome”
extreme starvation
Vitamin B5 (Pantothenic acid) Deficiency
113
```
Aminotransferase reactions (ALT and AST) - gluconeogenesis
Delta-aminolevulinate synthase (rate-limiting enzyme in heme synthesis)
Conversion of tryptophan to niacin
```
Pyridoxine (Vitamin B6)
114
Sideroblastic anemia (cannot incorporate iron into heme)
Dermatitis, glossitis, cheilosis/stomatitis, irritability, confusion
Toxicity can occur – peripheral neuropathy, dermatoses, photosensitivity dizziness, and nausea.
Vitamin B6 (Pyridoxine) deficiency
115
Cofactor for carboxylation enzymes:
Acetyl-CoA carboxylase (ACC)
Pyruvate carboxylase (PC)
Propionyl CoA carboxylase (PCC)Methylcrotonyl CoA (MCC)
Biotin (Vitamin B7)
116
Deficiency from excessive consumption of raw egg whites
Dermatitis around eyes, nose and mouth, conjunctivitis, alopecia and neurologic symptoms including lethargy and hallucinations
Vitamin B7 (Biotin) deficiency
117
coenzyme for 1-carbon transfer/methylation reactions, e.g., thymidylate synthase (de novo pyrimidine synthesis)
Folic acid (Vitamin B9)
118
Deficiency in pregnancy → neural tube defect (spina bifida amongst others)
Side effect of several drugs Phenytoin, sulfonamides, methotrexate
Macrocytic megaloblastic anemia
Homocysteinemia (cardiovascular disease, DVT, thromboembolism, stroke)
Vitamin B9 (Folic acid) deficiency
119
Homocysteine → methionine (Homocysteine methyltransferase )
| Methylmalonyl-CoA → succinyl CoA (Methymalonyl-CoA mutase )
Vitamin B12 (Cobalamin)
120
```
Caused by:
Pernicious anemia (most common cause)
Chronic pancreatitis
Long-term total vegetarian diet
Resection of terminal ileum
```
Manifestation:
Megaloblastic anemia
Neuropathies
Homocysteinemia (CV disease, DVT, stroke)
Vitamin B12 (Cobalamin) deficiency
121
Collagen synthesis, neurotransmitter synthesis (dopamine → norepinephrine), fatty acid transport, prostaglandin metabolism, nitric oxide synthesis
Enhances iron absorption in GI tract
Antioxidant
Ascorbic acid (Vitamin C)
122
Dietary deficiency from: devoid of citrus fruits and green vegetables
Clinical manifestations: Scurvy
Occurs in severely malnourished, poverty
Prominent cutaneous signs (petechiae, perifollicular hemorrhage, and bruising), gingivitis, arthralgias, and impaired wound healing
Vitamin C (Ascorbic acid) deficiency
123
Essential for normal fetal and childhood development, antioxidant free radical scavenger
Forms:
Alpha-tocopherol; gamma-tocopherol most common
Beta- and delta-tocopherol; and alpha-, beta-, gamma-, and delta-tocotrienols also exist
Vitamin E
124
Deficiency is rare:
Results in neuromuscular disorders and hemolysis
Fat malabsorption conditions (i.e., pancreatic exocrine insufficiency, cholestatic liver disease)
Vitamin E deficiency
125
Involved in carboxylation of glutamate residues (gamma-carboxylation)
Prothrombin (factor II), factors VII, IX and X, proteins C, S, Z
Osteocalcin
Vitamin K (Phylloquinone, Menaquinone)
126
Deficiency leads to bleeding issues, osteoporosis
| Interactions with blood thinners such as warfarin
Vitamin K deficiency
127
Main functions: vison and maintenance of epithelium
Vitamin A
```
Provitamin A carotenoids (in plants) – primarily beta-carotene – metabolized into vitamin A/retinal
Preformed vitamin A
Retinol
Retinoic acid
Retinal
Retinyl esters
Stored in liver as retinol
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128
Deficiency caused by:
Extreme malnutrition
South Asia and sub-Saharan Africa
Fat malabsorption and liver cirrhosis (most common in US)
Vitamin A deficiency
129
Night blindness
Xerophthalmia-> pathologic dryness of conjunctiva and cornea ->Bitot spots (areas of abnormal squamous cell proliferation and keratinization of conjunctiva) -> corneal xerosis and keratomalacia (softening)
Follicular hyperkeratosis
Frequent infections (pneumonia, bronchitis)
Toxicity: teratogenic in pregnancy
Vitamin A deficiency
130
Fatal genetic disorder in which both arms (B and T cells) of adaptive immune system are compromised.
Young patients often males because the most common form is X-linked
Mutations to the receptors shared by interleukins involved in development and differentiation of B and T cells
“Bubble boys” due to the need to be completely isolated from environment
Severe combined immunodeficiency (SCID)
ADA deficiency is the second most common most pronounced in lymphocytes that have the highest ADA activity
Leads to high levels of adenosine which is subsequently converted to AMP and ADP and then to dADP and dATP
Increased dATP inhibit the activity site of ribonucleotide reductases that in turn blocks the formation of all other dNDPs. Low levels of dNDP and dNTP impairs DNA synthesis and leads to the compromised immune system
131
as high levels of uric acid in the blood
Results in extremely painful deposits of sodium urate in the joints of extremities
Sodium urate deposits in the kidneys can cause damage.
Diets rich in purines (beans, spinach, lentils) along with alcohol, meat and seafood can trigger episodes
Gout
132
defects in HGPRT in purine salvage pathway and is a rare form of primary hyperuricemia.
Hyperuriciemia leads to gout, urate kidney stones, poor muscle control, mental retardation, and tendency for self-mutilation
Lesch-Nyhan syndrome
133
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Severe protein deficiency
Sufficient calories, but insufficient protein
enlarged fatty liver
Usually occurs after weaning
Edema of hands and feet
Light-colored skin
Thinning hair
Distended abdomen
Shiny skin
Ulcerating dermatoses
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Kwashiorkor syndrome
134
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Protein-calorie deficiency
Emaciated
Chronic diarrhea
Respiratory infections
Intellectual disability
Stunted growth
Apathy
No energy
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Marasmus
135
Primary Active Transport
P type ATPases – ATP is hydrolyzed, protein gets phosphorylated. (aspartate, conformational changes, ex. Na+/K+-ATPase, Ca2+-ATPase)
ABC Transporters – ATP is hydrolyzed, but does not phosphorylate the transporter (ex. P glycoproteins)
136
Na+/K+ ATPase
Extracellular: 3Na out,
Intracellular: 2 K in
137
Secondary Active Transport
moves molecules against concentration gradient in an energy-dependent, protein-assisted manner.
However, the source of energy is not ATP hydrolysis.
Thermodynamically unfavorable flow of one species of ion against a gradient coupled to favorable flow of another species down a gradient.
This gradient is typically established and maintained by the primary active transport mechanism.
E.g., Sodium-glucose transporter (SGLT).
E.g., Sodium calcium exchanger (NCX).
138
Secondary Transporters
Antiporter: Na/Ca exchanger
Symporter: lactose permease
Uniporter: Mitochondrial Ca transporter
139
Sodium-glucose transporter 1
The sodium glucose transporter (SGLT1) is present in the epithelial cells that line the small intestine and renal tubules.
Mediates unidirectional movement of Na+ and glucose across small intestine and renal tubules.
Movement of Na+ occurs down its gradient (downhill).
This provides energy to move glucose against its gradient (uphill).
The Na+ gradient is reset by the Na+/K+-ATPase
140
Na+-Ca2+ Exchanger (NCX)
antiporter.
Functions to maintain low levels of intracellular calcium in cells.
Imports 3Na+ down their concentration gradient and exports 1 Ca2+ against its gradient.
Uses the energy stored in the Na+ gradient.
141
Membrane proteins
1. Integral: embedded=polytopic transmembrane
2. Peripheral: loosely associated
3. Lipid-anchored: tethered
142
Membrane Lipids
1. Phospholipids: Glycerolipids, sphingolipids
2. Glycolipids: carbohydrate residues
3. Cholesterol: embedded
143
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psychomotor delay
low muscle tone (hypotonia)
Seizures
abnormal movements
Too much salivation
Swallowing difficulties
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malignant hyperphenylalaninemia
Dihydopteridine reductase
Impaired renewal of tetrahydrobiopterin
Decreased levels of dopamine, serotonin, and folate
Treatment:
Supplement: BH4 and folate
No phenylalanine
Meds to restore neurotransmitters
144
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Hypertonia/spasticity
Impaired development
Optic atrophy and blindness
Unexplained fevers
Seizures
Irritability
Eating problems
Deafness
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Krabbe's disease
Impairment of the GALC gene
Galactosylceramidase hydrolyzes galactosylceramide, an important component of myelin
Treatment:
Anticonvulsant medication to stop seizures
Muscle relaxer drugs (to help ease muscle spasms)
Physical therapy to help slow deterioration of muscles
Occupational therapy to help older children with common tasks, such as getting dressed and eating
Bone marrow transplant
Cord blood transplantation
145
Movement disorder
Usually caused by brain damage occurring before birth, or in the first 5 years of life
Symptoms are variable
Cerebral palsy
146
Secreted by adipose tissue in direct proportion to fat mass
Acts through the ___ receptor
Receptor expressed in hypothalamus
Regulates body weight
Inhibits food intake
Stimulates energy expenditure
Mice lacking ___ are obese but lose weight if given ___
Leptin
147
a peptide secreted by stomach, acts on regions of the hypothalamus to stimulate appetite through its receptor
Ghrelin
148
a family of peptide hormones secreted into the blood by cells in the duodenum and jejunum regions of the small intestine as a postprandial signal.
___ binds to its receptor, a G-protein-coupled receptor located in various peripheral neurons, that relay signals to the brain.
Binding initiates a signal-transduction pathway in the brain that generates a feeling of satiety.
Cholecystokinin (CCK)
