Lecture 48

Question 1

metabolism of other monosaccharides

Answer 1

• all use GLUT2 for transport into liver hepatocytes from blood stream
• once in hepatocytes, galactose converted to glycolipids and glycoproteins, glucose converted to glucose-6-phosphate, and fructose sent to glycolysis

pg 1236

Question 2

dietary sources of fructose

Answer 2

• naturally occuring whole foods: fruits (and fruit juices), honey, some veggies
• in processed sweeteners: sucrose (table sugar) and high fructose corn syrup (more soluble and enhances moisture)

pg 1238

Question 3

glucose vs fructose metabolism

Answer 3

• glucose: stimulates insulin release which is required for uptake via GLUT4, uses glucokinase, negative feedback regulation exists
• fructose: does NOT stimulate insulin release, insulin not required for uptake, uses fructokinase, NO negative feedback regulation (as long as fructose comes to liver, it will be phosphorylated)

pg 1239

Question 4

fructokinase

Answer 4

• required for 1st step in fructose metabolism
• expressed only in liver, kidney, and small intestinal mucosal cells
• irreversible reaction
• bypasses the PFK-1 regulatory step
• rate of phosphorylation is 10x greater than glucokinase
• converts fructose to fructose-1-phosphate

pg 1240

Question 5

glucokinase in the liver

Answer 5

• capable of phosphorylating fructose
• has a high K_m (low affinity) for fructose

pg 1240

Question 6

aldolase B

Answer 6

• required for 2nd step of fructose metabolism
• multiple aldolase isoenzymes, all of them can cleave fructose-1,6-bisphosphate (glycolysis)
• only aldolase B can cleave fructose-1-phosphate
• DHAP can directly enter glycolysis/gluconeogenesis
• glyceraldehyde is first phosphorylated to glyceraldehyde-3-phosphate
• breaks fructose-1-phosphate into 2 molecules (1 being glyceraldehyde)

pg 1241

Question 7

essential fructosuria

Answer 7

• deficiency of fructokinase
• autosomal recessive (1:130,000 births)
• benign condition
• fructose accumulates in urine
• asymptomatic because glucokinase will use fructose (only aware after checkin for reducing sugars in urine)

pg 1243

Question 8

hereditary fructose intolerance

Answer 8

• autosomal recessive (1:20,000 births)
• deficiency of aldolase B leads to intracellular trapping of fructose-1-phosphate
• causes severe hypoglycemia, vomiting, jaundice, hemorrhage, hepatomegaly, renal dysfunction, hyperuricemia, and lactic acidemia
• fructose, sucrose, and sorbitol can cause hepatic failure and death
• treatment: removal of fructose and sucrose from diet
• fructose-1-phosphate has not other routes to metabolize in cells, all phosphate will be taken up, NO ATP production

pg 1244

Question 9

polyol pathway in liver

Answer 9

metabolizes polyols to fructose

• aldose reductase: found in many tissues, relatively nonspecific (reduces glucose to sorbitol -> a polyol)
• sorbitol dehydrogenase: found ONLY in liver (to metabolize sorbitol from diet) and seminal vesicles (sperm cells use fructose as fuel)

pg 1246

Question 10

polyols as sugar replacements

Answer 10

• sugar alcohols as bulk sweeteners
• xylitol provides the same level as sweetness as table sugar, but roughly 40% fewer calories
• commonly used as a sweetener in toothpaste, sugar-free chewing gum, and mints
• found in small amounts in berries, seaweed, yeast, and some types of mushrooms

pg 1246

Question 11

polyol pathway in other tissues

Answer 11

• when aldose reductase is present, excess glucose is converted to sorbitol
• sorbitol is final product (NO sorbitol dehydrogenase)

pg 1247

Question 12

sorbitol in diabetes mellitus (T1 and T2)

Answer 12

• in hyperglycemic conditions, excess glucose is readily converted to sorbitol which can NOT be metabolized further in cells that do not express sorbitol dehydrogenase
• sorbitol accumulation results in osmotic uptake of water
• accounts for some symptoms seen in diabetic patients -> cataracts, retinopathy, nephropathy, and peripheral neuropathy

pg 1247

Question 13

dietary galactose

Answer 13

comes from lactose in dairy products

pg 1249

Question 14

galactose metabolism in liver

Answer 14

• galactose converted to galactose-1-P by galactokinase (requires ATP)
• galactose 1-P uridylyltransferase (GALT) uses both galactose-1-P and UDP-glucose to form UDP-galactose and glucose-1-P
• UDP-galactose is used to form glycolipids, glycoproteins, and glycosaminoglycans
• UDP-galactose also used to form lactose

pg 1250

Question 15

when/where is UDP-galactose converted to lactose?

Answer 15

UDP-galactose convered to lactose in breast milk during lactation

pg 1251

Question 16

lactose synthesis in humans

Answer 16

• produced by lactating mammary glands
• synthesized in golgi apparatus
• enzyme: lactose synthase (UDP-galactose:glucose galactosyltransferase)

pg 1252

Question 17

lactose synthase (UDP-galactose:glucose galactosyltransferase)

Answer 17

• complex of 2 proteins
• protein A: β-D-galactosyltransferase found in a number of tissues
• protein B: α-lactalbumin
• protein B only expressed in mammary glands and its synthesis is stimulated by the peptide hormone prolactin
• results in the production of lactose

pg 1252

Question 18

galactokinase deficiency

Answer 18

• rare autosomal-recessive disorder
• causing elevation of galactose in blood (galactosemia) and urine (galactosuria)
• causing galactitol accumulation if galactose present in diet
• elevated galactitol causing cataracts
• treatment: dietary restriction of galactose

pg 1253

Question 19

aldose reductase

Answer 19

• aldose reductase converts galactose to galactitol (polyol of galactose) using NADPH
• present in the kidneys, retina, lens, nerve tissue, seminal vesicles, and ovaries
• physiologically unimportant in galactose metabolism unless galactose levels are high (as in galactosemia)
• elevated galactitol causing cataracts

pg 1254

Question 20

classic galactosemia

Answer 20

• galactose-1-phosphate uridylyltransferase deficiency
• severe condition -> autosomal-recessive disorder
• causes galactosemia and galactosuria
• accumulation of galactose-1-P and galactitol in the liver, brain, and eyes causing damage and cataracts
• prenatal diagnosis possible by chorionic villus sampling; newborn screening available
• treatment: removal of galactose (lactose) from diet
• despite adequate treatment, at risk for catacts, developmental delays, and premature ovarian failure

pg 1255

Question 21

galactose-1-phosphate uridylyltransferase vs fructose-1,6-bisphosphatase deficiency

Answer 21

• symptoms appear shortly after first feeding for galactose
• after long fasting period for fructose

pg 1255