Aspects of Carbohydrate Metabolism in Developing Brain

Baquer, Najma Zaheer; Hothersall, John S.; McLean, Patricia; Greenbaum, A. L.

doi:10.1111/j.1469-8749.1977.tb08027.x

Cited by 57 publications

(27 citation statements)

References 73 publications

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“…The PPP has been formulated with and without TAL, and, indeed, organisms lacking TAL have been documented (7,8). Enzymatic activity (31)(32)(33)(34)(35)(36)(37) and expression of TAL is regulated in a tissue-specific manner (9,(38)(39)(40). TAL catalyzes the transfer of a three-carbon fragment, corresponding to dihydroxyacetone, from S7P and fructose 6-phosphate to D-glyceraldehyde 3-phosphate and Derythrose 4-phosphate in the forward and reverse reactions, respectively (Fig.…”

Section: Discussionmentioning

confidence: 99%

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

Perl

Qian²,

Chohan³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Fertility of spermatozoa depends on maintenance of the mitochondrial transmembrane potential (⌬ m), which is generated by the electron-transport chain and regulated by an oxidation-reduction equilibrium of reactive oxygen intermediates, pyridine nucleotides, and glutathione (GSH). Here, we report that male mice lacking transaldolase (TAL) ؊/؊ are sterile because of defective forward motility. TAL ؊/؊ spermatozoa show loss of ⌬m and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH. Mitochondria constitute major Ca 2؉ stores; thus, diminished mitochondrial mass accounts for reduced Ca 2؉ fluxing, defective forward motility, and infertility. Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca 2؉ levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and ␥-glutamyl transferase. Microarray analyses of gene expression in the testis, caput, and cauda epididymidis of TAL ؉/؉ , TAL ؉/؊ , and TAL ؊/؊ littermates confirmed a dominant impact of TAL deficiency on late stages of sperm-cell development, affecting the electrontransport chain and GSH metabolism. Stimulation of de novo GSH synthesis by oral N-acetyl-cysteine normalized the low fertility rate of TAL ؉/؊ males without affecting the sterility of TAL ؊/؊ males. Whereas TAL ؊/؊ sperm failed to fertilize TAL ؉/؉ oocytes in vitro, sterility of TAL ؊/؊ sperm was circumvented by intracytoplasmic sperm injection, indicating that TAL deficiency influenced the structure and function of mitochondria without compromising the nucleus and DNA integrity. Collectively, these data reveal an essential role of TAL in sperm-cell mitochondrial function and, thus, male fertility. F orward motility and fertility of spermatozoa depend on production of reactive oxygen intermediates (ROIs) (1) and maintenance of the mitochondrial transmembrane potential (⌬ m ) (2, 3). ⌬ m is generated by the electron-transport chain and subject to regulation by an oxidation-reduction equilibrium of ROI, pyridine nucleotides (NADH͞NAD ϩ NADPH͞NADP), and reduced glutathione (GSH) (4). In turn, NADPH, a reducing equivalent required for biosynthetic reactions and regeneration of GSH from its oxidized form, is produced by the pentose phosphate pathway (PPP) (5). The PPP was originally formulated based on metabolites and enzymes detected in yeast (6). Thus, PPP comprises two separate oxidative and nonoxidative phases. Enzymes of the oxidative phase, glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase, can generate both ribose 5-phosphate (R5P) and NADPH. Although enzymes of the nonoxidative phase, transketolase (TK) and transaldolase (TAL), can convert R5P into glucose 6-phosphate (G6P) for the oxidative phase, and, thus, indirectly, these enzymes can also contribute to the generation of NADPH, the significance of the nonoxidative branch is less well established. Certain organisms (7,8) and mammalian tissu...

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Section: Discussionmentioning

confidence: 99%

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

Perl

Qian²,

Chohan³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Pentose phosphate pathway Baquer et al (1977) discussed the connection between pentose phosphate pathway activity and the presence of the neurotransmitters, that it could be related either to the process of transmission itself or to the metabolism of the neurotransmitters. It was proposed that the aldehydes produced by the action of MAO on the catecholamine were reduced to the corresponding alcohols by NADPH-linked aldehyde reductase.…”

Section: Experimental Approaches To Study Of Metabolic Pathwaysmentioning

confidence: 99%

A metabolic and functional overview of brain aging linked to neurological disorders

et al. 2009

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Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

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“…Enzymatic activity of TAL is regulated in a tissuespecific (35, 37, 58 -63) and developmentally-specific manner (7,64). Apoptosis pathways dependent on generation of ROI can be regulated by TAL through control of the balance between the two branches of the PPP and its overall output as measured by NADPH and GSH production (23).…”

Section: Regulation Of the Ppp And Apoptosis By Talmentioning

confidence: 99%

“…Age-related immune dysfunctions including lymphocyte proliferation and macrophage phagocytosis correlate with impaired glucose metabolism via PPP (4). The PPP is important in host defense mechanisms in all tissues against oxidative stress (5), in embryogenesis/morphogenesis (6), neurulation (7), myelination (8), inflammation (9), lymphocyte activation (10,11), phagocytosis (4,12), radiation resistance of malignant tumors (13), and toxicity of high glucose concentrations in diabetes mellitus (14). Many of these processes are associated with apoptosis, a fundamental form of programmed cell death (PCD) (15).…”

Section: Introductionmentioning

confidence: 99%

The pathogenesis of transaldolase deficiency

Perl¹

2007

IUBMB Life

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SummaryThe signaling networks that mediate cell growth, differentiation, and survival are dependent on complex metabolic and redox pathways. Metabolism of glucose through the pentose phosphate pathway (PPP) fulfills two unique functions: formation of ribose 5-phosphate for the synthesis of nucleotides, RNA, and DNA in support cell growth and formation of NADPH for biosynthetic reactions and neutralization of reactive oxygen intermediates (ROI). Balancing of NADPH and ROI levels by the PPP enzyme transaldolase (TAL) regulates the mitochondrial trans-membrane potential (Dw m ), a critical checkpoint of ATP synthesis and cell survival. While complete deficiency of glucose 6-phosphate dehydrogenase (G6PD) or transketolase (TK) is lethal, TAL-deficient mice developed normally with the exception of male sterility due to structural and functional damage of sperm cell mitochondria. Recently, two cases of complete TAL deficiency have been reported in patients with liver cirrhosis which results from increased cell death of hepatocytes. Delineation of the cell type-specific role that TAL plays in the PPP and cell death signal processing will be critical for understanding the pathogenesis of TAL deficiency.

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Aspects of Carbohydrate Metabolism in Developing Brain

Cited by 57 publications

References 73 publications

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

A metabolic and functional overview of brain aging linked to neurological disorders

The pathogenesis of transaldolase deficiency

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