Fructose and Pentose Phosphate Pathway Flashcards
Galactose and fructose have the same chemical formula as ____.
The disaccharides , ____ and ____ are hydrolyzed two monosaccharides by enzymes at the brush border of intestinal epithelial cells
Glucose
Lactose
Sucrose
Most fructose is ingested in the form of the disaccharide ___. It is converted into glycolytic intermediates which can be used for generating energy, or stored as glycogen or fatty acids.
Sucrose
Fructose can be found in ____. Sucrose is found in ____.
Honey
Fruit
We can synthesize fructose from glucose through the ____ pathway.
Polyol
Fructose is an ____ of glucose.
Isomer
The polyol pathways occurs normally in seminal vesicles to produce fructose as an ___ source for sperm
Energy
Cataracts is caused by hyperglycemia, the polyol pathway can lead to elevated sorbitol and ___ levels in the eye, causing high pressure and glycated lens.
Fructose
Polyol pathway:
In the lumen of the gut, the ____/___ complex breaks down disaccharide sucrose into fructose and glucose.
Sucrase/isomaltase
Dietary fructose is taken up from the lumen of the gut by ____ transporters.
GLUT5
Transport of fructose across the apical membrane is through ____ transporter
GLUT2
Fructose is metabolized primarily in the ____.
Liver
Fructose metabolism first step:
Fructose is phosphorylated by _____ into fructose 1-phosphate
Fructokinase
The 4th step of glycolysis:
The ___ enzyme cleaves fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate.
Liver cells express ____ _, which can also use fructose 1-phosphate as a substrate.
Aldolase
Aldolase B
Glycolysis 4th step:
Only Aldolase B in the liver can use _____ as a substrate. Aldolase B cleaves it into dihydroxyacetone phosphate and glyceraldehyde.
Fructose 1-phosphate
The products of fructose metabolism can enter _____. Excess fructose can be stored either as glycogen or fat.
Glycolysis
Which major regulatory step in glycolysis is bypassed in fructose 1-phosphate catabolism?
Phosphofructokinase-1 phosphorylates Fructose 6-P into fructose 1,6-bis-P
In muscle, fructose can also be phosphorylated directly by _____, (although glucose is its preferred substrate), producing Fructose 6-phosphate
Hexokinase
The disaccharide lactose is the principe source of ____ in our diet. ____ can be converted to glucose 1 phosphate for storage as glycogen or used in glycolysis.
Galactose
Galactose
UDP-galactose is an important precursor for _____ of proteins and phospholipids
Glycosylation
The sugar of uridine diphosphate glucose (UDP-glucose) can be epimerized to _____, which is a substrate for the synthesis of ____, the primary source of galactose in our diets.
UDP-galactose
Lactose
Lactose synthesis:
Lactose is digested in the lumen of the gut by the enzyme ____ which cleaves the disaccharide lactose into the monosaccharides galactose and glucose.
Lactase
Galactose is transported through ____ and the ____ (secondary active transport system).
GLUT2
SGLT
The first step in Intracellular galactose metabolism is its phosphorylation by ____ into galactose 1-phosphate.
Galactokinase
____ ____ ____ transferase converts UDP-glucose and galactose 1-phosphate to UDP-galactose and glucose 1-phosphate
Galactose 1-phosphate uridyl
Glucose 1-phosphate produced by transferase can be converted to _____ a substrate for glycolysis, pentose phosphate pathway, fatty acid synthesis, etc.
Glucose 6-phosphate
_____ interconverts UDP-galactose and UDP-glucose. UDP-glucose can be used as a substrate for ____ synthesis or can be used to sustain ____ metabolism.
Epimerase
Glycogen
Galactose
The end product of galactose metabolism is ___ ____, which can enter glycogenesis directly or be converted to glucose 6-phosphate for glycolysis or export
Glucose 1-phosphate
About 10% of the glucose 6-phosphate in each cell is diverted to the ___ ___ pathway.
Pentose phosphate
The products of the pentose phosphate pathway are reduced ____ and ____ ____ (used in nucleotide biosynthesis).
NADPH
5carbon sugars
About 10% of ____ is metabolized through the pentose phosphate pathway.
Glucose
Pentose phosphate pathway has two purposes:
Generation of ____ and ____.
NADPH
Five carbon sugars
Five carbon sugars are used primarily for synthesizing ____.
Nucleotides
The reducing power of NADPH is used for ___ ___, ___, and ____ synthesis. Also used for oxidation of toxins by ____ ____ enzymes. Also used for generation of reduced ____.
Fatty acid
Cholesterol
Nucleotide
Cytochrome P450
Glutathione
The pentose phosphate pathway is very active in the ____, ___, ____ mammary gland, ___ ___, and ___ ___ cells.
Liver
Adipose
Lactating
Adrenal cortex
Red blood
The Pentose phosphate pathway is divided into the ____ phase and the ____ phase.
Oxidative
Regenerative
The oxidative phase of the pentose phosphate pathway converts glucose to _____. It generates ____ in the process. The key enzyme is ___ ___. These reactions are not reversible
Ribulose 5-phosphate
NADPH
6-phosphate dehydrogenase
The regenerative phase of the pentose phosphate pathway converts ribulose 5-phosphate to ____ ____ and glycolysis intermediates. It is reversible. The key enzymes are _____ and ____.
These glycolysis intermediates can be used to generate five carbon sugars for ____ ___.
Ribose 5-phosphate
Transketolase
Transaldolase
Nucleotide synthesis
The first oxidation is catalyzed by ___ ____ ____. Glucose 6-phosphate is oxidized to 6-phosphoglucano-lactone. NADP+ is reduced to ____.
Glucose 6-phosphate dehydrogenase
NADPH
One of the most important functions of the NADPH, produced by the pentose phosphate pathway is to maintain _____ in the reduced state.
Glutathione
Glutathione is a tripeptide: ___ ___, ___, ___. Glutathiones role is to neutralize ___ ___ so it does not damage the cell.
Glutamic acid, cysteine, glycine
Oxidative stress
The sulfide on glutathione can be oxidized by forming a ____ ___ with another glutathione.
Disulfide bond
The rescuing power of NADPH is used to maintain _____ in reduced state so that it can remove ___ ____ from the cell.
Glutathione
Hydrogen peroxide
Diagram of glutathione function:
Regenerative phase:
Ribulose 5-phosphate is isomerized into ___ ____ or epimerized into ___ ____. These two molecules feed into the regenerative phase of PPP.
Ribose 5-phosphate
Xylulose 5-phosphate
____ ____ can exit the PPP and be used for nucleotide synthesis.
____ ___ is a transcriptional regulator.
Ribose 5-phosphate
Xylulose 5-phosphate
Regenerative phase key enzymes:
1. Transketolase transfers ___ ___ groups and uses ____ __ derived from thiamine pyrophosphate as a cofactor.
2. Transaldolase transfers ___ ___ groups
Two carbon
Vitamin B1
Three carbon
The goal of the regenerative phase is to allow the five carbon sugar to be turned into ___ ___ in situations when nucleotide synthesis is not required.
Glycolysis intermediates
Glycolytic intermediates all have either ___ carbons or ___ carbons.
6
3
When nucleotide synthesis is required, the reverse reactions of the PPP convert glycolysis intermediates into ___ ___ ____.
5 carbon sugars
Regenerative phase:
Transketolase reactions transfer two carbon groups
Regenerative phase:
Transaldolase reactions transfer three carbon groups
PPP summary:
When carbohydrates are abundant, the liver converts them to fatty acids and exports them as ____ for storage.
VLDL
The carbohydrate response element binding protein ( _____) is a transcription factor. It is inhibited by phosphorylation by ___ ___ __ and adenosine monophosphate activated kinase (_____).
ChREBP
Protein kinase A (PKA)
AMPK
Xylulose 5-phosphate (X5P) acts as an ____ ____ of protein phosphatase-2 (PP2A) which removed inhibitory phosphates from ChREBP, causing it’s translocation to the nucleus
Allosteric activator
Xylulose 5-phosphate _____ carbohydrate response elements (ChoRE) in gene promoters, while ____ enhances transcription through sterol response elements and E-boxes. ____ ____ expression is thus coordinated by metabolic and endocrine signals.
Activates
Insulin
Lipogenic gene
Lipogenic genes upregulated by ChREBP:
Pyruvate kinase
Malic enzyme
Citrate Lyase
Acetyl CoA
Carboxylase
Fatty acid synthase
Review
Xylulose 5-phosphate promotes transcription of genes that convert ____ to ___.
Carbohydrates
Fat
Inborn errors of fructose metabolism: essential fructosuria is caused by inherited loss of function mutations in ____. It is benign. The only significant clinical finding is ___ ___ in the urine, which may be confused for diabetes.
Fructokinase
Reducing sugars
Without fructokinase, fructose is metabolized through ____ or eliminated in the urine.
Hexokinase
Inborn errors of fructose metabolism:
____ ___ ____ is caused by inherited mutations in aldolase B. This condition is much more serious than essential fructosuria. This disease is silent until fructose is ingested.
Hereditary fructose intolerance
Hereditary fructose intolerance:
When patients ingest fructose, all intracellular phosphate gets trapped in ____ ___ because it cannot be metabolized. When a cells phosphate pool is trapped, ____ synthesis is impaired.
Fructose 1-phosphate
ATP
Clinical signs of hereditary fructose intolerance:
Vomiting, lethargy, aversion to fruit, recurrent hypoglycemic episodes, failure to thrive, hepatic failure
Disorders of galactose metabolism:
In ___ ___, dietary lactose is not broken down two monosaccharides in the small intestine. Gut bacteria Ferment lactose to lactic acid and water enters the lumen of the gut to offset the increased lactate.
Lactase deficiency
Lactase deficiency aka ___ ___ results in diarrhea when dairy sugars are consumed.
Lactose intolerant
_____ lactase deficiency is an autosomal recessive condition in which lactase activity declines over many years
Primary
____ lactase deficiency is due to damage of brush border of intestinal enterocytes due to intestinal disease
Secondary
____ lactase deficiency is a very rare genetic condition. It is the complete absence of lactase.
Congenital
Disorders of galactose metabolism:
_____ can result from inborn error of metabolism involving galactokinase, transferase, and epimerase
Galactosemia
______ ____: nonclassical, galactose, accumulates, and is converted to galactitol through polyol pathway in the eyes leading to Cataracts
Galactokinase deficiency
____ ____ ___ _____ deficiency: classical galactosemia. It is an autosomal recessive and very serious. It presents with jaundice, hepatomegaly, hypoglycemia, lethargy, and FTT
Galactose 1-phosphate uridyl transferase
____ ___: the symptoms and prognosis are similar to transferase deficiency. The treatment is to restrict, but not to eliminate galactose from the diet.
Epimerase deficiency
In transferase deficiency, the treatment is:
Im Epimerase deficiency, the treatment is:
Galactose free diet
Galactose restricted diet, very low amounts of galactose
Why different treatments?
We need UDP galactose as a substrate for glycosylation reactions. With transferase deficiency, we can make UDP galactose from glucose. With a epimerase deficiency, the only way to make UDP galactose is from dietary galactose.
_____ ____ ____ deficiency: is a common inborn error of metabolism as an X-linked trait where the enzyme is not completely inactive. It can provide enough flux through the pentose phosphate, oxidative Fais to provide reducing power for glutathione. Affected people are asymptomatic until they are exposed to elevated oxidative stress.
Glucose 6-phosphate dehydrogenase
In people with glucose 6 phosphate, dehydrogenase deficiency, when they are exposed to oxidative stress their capacity to regenerate ____ is limited. Red blood cells are particularly affected by oxidative stress, causing ____ ___.
NAPDH
Hemolytic anemia
Substances that can cause hemolytic anemia in deficient individuals:
Review
